Inotuzumab Ozogamicin and Frontline Chemotherapy in Treating Young Adults With Newly Diagnosed B Acute Lymphoblastic Leukemia

A Phase III Trial to Evaluate the Efficacy of the Addition of Inotuzumab Ozogamicin (a Conjugated Anti-CD22 Monoclonal Antibody) to Frontline Therapy in Young Adults (Ages 18-39 Years) With Newly Diagnosed Precursor B-Cell ALL

This partially randomized phase III trial studies the side effects of inotuzumab ozogamicin and how well it works when given with frontline chemotherapy in treating patients with newly diagnosed B acute lymphoblastic leukemia. Monoclonal antibodies, such as inotuzumab ozogamicin, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving inotuzumab ozogamicin with chemotherapy may work better in treating young adults with B acute lymphoblastic leukemia.

Study Overview

• Status: Suspended
• Conditions: B Acute Lymphoblastic Leukemia
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Daunorubicin Hydrochloride; Drug: Cyclophosphamide; Drug: Mercaptopurine; Drug: Vincristine Sulfate; Drug: Dexamethasone; Drug: Thioguanine; Biological: Rituximab; Drug: Doxorubicin; Biological: Inotuzumab Ozogamicin; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Allopurinol; Drug: Cytarabine; Drug: Pegylated L-Asparaginase; Drug: Methotrexate

Detailed Description

PRIMARY OBJECTIVES:

I. To confirm tolerability of the combination regimen with the addition of inotuzumab ozogamicin to the pediatric-inspired regimen of cancer and leukemia group B (CALGB) 10403.

II. To determine whether the addition of inotuzumab ozogamicin significantly improves the event-free survival (EFS) in patients who achieve an induction response achieved with the pediatric-inspired regimen of CALGB 10403, without censoring for transplant. (Phase III)

SECONDARY OBJECTIVES:

I. To determine the impact of inotuzumab ozogamicin on disease-free (DFS) and overall survival (OS) in patients who achieve an induction response.

II. To determine whether the addition of inotuzumab ozogamicin significantly improves the event-free survival (EFS) in patients who achieve an induction response achieved with the pediatric-inspired regimen of CALGB 10403, with censoring for transplant.

III. To determine the impact of inotuzumab ozogamicin on minimal residual disease (MRD) and correlate this with the EFS, DFS and OS.

IV. To determine the prognosis based on patients' low-density array (LDA) gene signature in terms of EFS, DFS, and OS after treatment with or without inotuzumab ozogamicin when added to the C10403 backbone regimen.

V. To evaluate the toxicity and tolerability of the addition of inotuzumab ozogamicin to the pediatric-inspired regimen of CALGB 10403.

TERTIARY OBJECTIVES:

I. To assess both the correlation of MRD post-induction and at sequential timepoints with LDA signature.

II. To evaluate the influence of MRD status (detectable vs. not and as a continuous measure) in relation to EFS both in the univariate setting as well as adjusting for other clinical features including initial white blood cell (WBC), ethnicity, gender and age at diagnosis.

III. To evaluate the impact of inotuzumab ozogamicin (inotuzumab) on the kinetics of MRD during treatment with inotuzumab in patients randomized to the experimental treatment arm.

IV. To perform genomic analyses to identify and evaluate the incidence and clinical significance of recurring novel fusion genes including those associated with the BCR-ABL1-like signature and to correlate with MRD status, CR rate, EFS and OS.

V. To assess whether rs4958351 is correlated with L-asp allergic reaction in the adolescent and young adult (AYA) population.

VI. To assess the incidence of inherited genetic variants in the GR1A1, CEP72, CPA2, TPMT, NUDT15, GRIN3A, GRIK1, and other genes (which can be found using a whole genome association study [GWAS]), are correlated with increased rates of target toxicities including peripheral neuropathy, hepatotoxicity, pancreatitis, myelosuppression, neurotoxicity, thrombosis, and osteonecrosis, and correlate with treatment discontinuation and other clinical response parameters including complete response (CR) rate, EFS, and OS.

VII. To evaluate asparaginase pharmacokinetics in adolescents and young adults, and investigate its correlation with toxicities and treatment outcomes.

VIII. To investigate the effect of anti-polyethylene glycol (PEG) and anti-agouti signaling protein (ASP) antibodies (PEG-ASP) on ASP enzyme activity.

IX. To measure adherence to oral 6 mercaptopurine (MP) and methotrexate in AYAs with acute lymphoblastic leukemia (ALL) and to examine sociodemographic and behavioral determinants of adherence.

X. To determine the impact of adherence on risk of relapse among AYAs with ALL.

OUTLINE:

COURSE I (REMISSION INDUCTION THERAPY): All patients receive allopurinol orally (PO) once daily until peripheral blasts and extramedullary disease are reduced and cytarabine intrathecally (IT) over 1 minute on day 1. Patients also receive daunorubicin hydrochloride intravenously (IV) and vincristine sulfate IV on days 1, 8, 15 and 22, dexamethasone PO or IV twice daily (BID) on days 1-7 and 15-21, pegylated L-aspiraginase IV on day 4, 5, or 6, and methotrexate IT over 1 minute on days 8 and 29. Patients with central nervous system (CNS) 3 disease receive methotrexate IT over 1 minute also on days 15 and 22. All patients then undergo bone marrow aspirate and biopsy on day 29.

Patients with response to remission induction therapy are randomized to 1 of 2 arms. Patients with no response are omitted from the study.

ARM I:

COURSE II (REMISSION CONSOLIDATION CHEMOTHERAPY): Patients receive cyclophosphamide IV on days 1 and 29, cytarabine IV or SC on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine PO on days 1-14 and 29-42, and vincristine sulfate IV on days 15, 22, 43, and 50. Patients also receive pegylated L-aspiraginase IV on days 15 and 43, and methotrexate IT on days 1, 8, 15, and 22. Patients with CNS3 receive methotrexate IT only on days 1 and 8. CD20 positive (+) patients receive rituximab IV on days 1, 8, 29, and 36. Patients then undergo bone marrow aspirate and biopsy on day 56.

COURSE III (INTERIM MAINTENANCE CHEMOTHERAPY): Patients receive vincristine sulfate IV on days 1, 11, 21, 31, and 41, methotrexate IV and IT on days 1, 11, 21, 31, and 41, and pegylated L-aspiraginase IV on days 2 and 22. CD20+ patients receive rituximab IV on days 1 and 11.

COURSE IV (DELAYED INTENSIFICATION): Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50, dexamethasone PO or IV BID on days 1-7 and 15-21, doxorubicin IV on days 1, 8, and 15, and pegylated L-aspiraginase IV on day 4, 5, or 6 and day 43. Patients also receive cyclophosphamide IV on day 29, cytarabine IV or SC on days 29-32 and 36-39, thioguanine PO on days 29-42 and methotrexate IT on days 1, 29, and 36. CD20+ patients receive rituximab IV on days 1 and 8. Patients then undergo bone marrow aspirate and biopsy on day 50.

COURSE V (MAINTENANCE THERAPY): Patients receive vincristine sulfate IV on days 1, 29, and 57, dexamethasone PO or IV BID on days 1-5, 29-33, and 57-61, and mercaptopurine PO on days 1-84. Patients also receive methotrexate IT or PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for up to 3 years in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive inotuzumab ozogamicin IV on days 1, 8, and 15 and undergo bone marrow aspirate and biopsy on day 28. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive remission consolidated chemotherapy, interim maintenance chemotherapy, delayed intensification, and maintenance therapy as in Arm I.

After completion of study treatment, patients are followed up every month for the first year, every 2 months for the second year, every 3 months for the third year, and every 6 months for the fourth through tenth year.

• Study Type: Interventional
• Enrollment (Estimated): 310
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • QEII Health Sciences Centre/Nova Scotia Health Authority
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital and Cancer Center-General Campus
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • Alaska
    • Anchorage, Alaska, United States, 98508
      • Anchorage Associates in Radiation Medicine
    • Anchorage, Alaska, United States, 99508
      • Alaska Breast Care and Surgery LLC
    • Anchorage, Alaska, United States, 99508
      • Alaska Oncology and Hematology LLC
    • Anchorage, Alaska, United States, 99508
      • Alaska Women's Cancer Care
    • Anchorage, Alaska, United States, 99508
      • Anchorage Oncology Centre
    • Anchorage, Alaska, United States, 99508
      • Katmai Oncology Group
    • Anchorage, Alaska, United States, 99508
      • Providence Alaska Medical Center
    • Anchorage, Alaska, United States, 99504
      • Anchorage Radiation Therapy Center
    • Fairbanks, Alaska, United States, 99701
      • Fairbanks Memorial Hospital
  • Arizona
    • Kingman, Arizona, United States, 86401
      • Kingman Regional Medical Center
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital in Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic in Arizona
  • Arkansas
    • Fort Smith, Arkansas, United States, 72903
      • Mercy Hospital Fort Smith
  • California
    • Antioch, California, United States, 94531
      • Kaiser Permanente-Deer Valley Medical Center
    • Arroyo Grande, California, United States, 93420
      • PCR Oncology
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
    • Clovis, California, United States, 93611
      • Community Cancer Institute
    • Clovis, California, United States, 93611
      • University Oncology Associates
    • Costa Mesa, California, United States, 92627
      • UC Irvine Health Cancer Center-Newport
    • Dublin, California, United States, 94568
      • Kaiser Permanente Dublin
    • Fremont, California, United States, 94538
      • Kaiser Permanente-Fremont
    • Fresno, California, United States, 93720
      • Kaiser Permanente-Fresno
    • Fresno, California, United States, 93720
      • Fresno Cancer Center
    • Modesto, California, United States, 95356
      • Kaiser Permanente-Modesto
    • Oakland, California, United States, 94611
      • Kaiser Permanente-Oakland
    • Oakland, California, United States, 94611
      • Kaiser Permanente Oakland-Broadway
    • Orange, California, United States, 92868
      • UC Irvine Health/Chao Family Comprehensive Cancer Center
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Institute Palo Alto
    • Rancho Cordova, California, United States, 95670
      • Kaiser Permanente-Rancho Cordova Cancer Center
    • Redwood City, California, United States, 94063
      • Kaiser Permanente-Redwood City
    • Redwood City, California, United States, 94063
      • Kaiser Permanente- Marshall Medical Offices
    • Richmond, California, United States, 94801
      • Kaiser Permanente-Richmond
    • Rohnert Park, California, United States, 94928
      • Rohnert Park Cancer Center
    • Roseville, California, United States, 95678
      • The Permanente Medical Group-Roseville Radiation Oncology
    • Roseville, California, United States, 95661
      • Kaiser Permanente-Roseville
    • Sacramento, California, United States, 95817
      • University of California Davis Comprehensive Cancer Center
    • Sacramento, California, United States, 95814
      • Kaiser Permanente Downtown Commons
    • Sacramento, California, United States, 95823
      • Kaiser Permanente-South Sacramento
    • Sacramento, California, United States, 95823
      • South Sacramento Cancer Center
    • Sacramento, California, United States, 95825
      • Kaiser Permanente - Sacramento
    • San Francisco, California, United States, 94115
      • Kaiser Permanente-San Francisco
    • San Jose, California, United States, 95119
      • Kaiser Permanente-Santa Teresa-San Jose
    • San Leandro, California, United States, 94577
      • Kaiser Permanente San Leandro
    • San Rafael, California, United States, 94903
      • Kaiser San Rafael-Gallinas
    • San Rafael, California, United States, 94903
      • Kaiser Permanente-San Rafael
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Medical Center - Santa Clara
    • Santa Rosa, California, United States, 95403
      • Kaiser Permanente-Santa Rosa
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente Cancer Treatment Center
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente-South San Francisco
    • Stockton, California, United States, 95210
      • Kaiser Permanente-Stockton
    • Vacaville, California, United States, 95688
      • Kaiser Permanente Medical Center-Vacaville
    • Vallejo, California, United States, 94589
      • Kaiser Permanente-Vallejo
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente-Walnut Creek
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers-Aurora
    • Aurora, Colorado, United States, 80012
      • The Medical Center of Aurora
    • Boulder, Colorado, United States, 80301
      • Boulder Community Hospital
    • Boulder, Colorado, United States, 80303
      • Boulder Community Foothills Hospital
    • Boulder, Colorado, United States, 80304
      • Rocky Mountain Cancer Centers-Boulder
    • Centennial, Colorado, United States, 80112
      • Rocky Mountain Cancer Centers - Centennial
    • Denver, Colorado, United States, 80218
      • Presbyterian - Saint Lukes Medical Center - Health One
    • Denver, Colorado, United States, 80218
      • SCL Health Saint Joseph Hospital
    • Denver, Colorado, United States, 80220
      • Rose Medical Center
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers-Midtown
    • Denver, Colorado, United States, 80220
      • Rocky Mountain Cancer Centers-Rose
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
    • Denver, Colorado, United States, 80204
      • Cancer Center of Colorado at Sloan's Lake
    • Denver, Colorado, United States, 80209
      • The Women's Imaging Center
    • Denver, Colorado, United States, 80206
      • National Jewish Health-Main Campus
    • Denver, Colorado, United States, 80220
      • Western Surgical Care
    • Englewood, Colorado, United States, 80113
      • Mountain Blue Cancer Care Center - Swedish
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Englewood, Colorado, United States, 80113
      • Rocky Mountain Cancer Centers - Swedish
    • Englewood, Colorado, United States, 80113
      • The Melanoma and Skin Cancer Institute
    • Golden, Colorado, United States, 80401
      • National Jewish Health-Western Hematology Oncology
    • Grand Junction, Colorado, United States, 81501
      • Saint Mary's Hospital and Regional Medical Center
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Lafayette, Colorado, United States, 80026
      • Good Samaritan Medical Center
    • Lakewood, Colorado, United States, 80228
      • Rocky Mountain Cancer Centers-Lakewood
    • Littleton, Colorado, United States, 80120
      • Rocky Mountain Cancer Centers-Littleton
    • Lone Tree, Colorado, United States, 80124
      • Sky Ridge Medical Center
    • Lone Tree, Colorado, United States, 80124
      • Rocky Mountain Cancer Centers-Sky Ridge
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
    • Thornton, Colorado, United States, 80260
      • Rocky Mountain Cancer Centers-Thornton
    • Thornton, Colorado, United States, 80260
      • National Jewish Health-Northern Hematology Oncology
    • Wheat Ridge, Colorado, United States, 80033
      • SCL Health Lutheran Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Smilow Cancer Hospital Care Center at Saint Francis
    • New Haven, Connecticut, United States, 06520
      • Yale University
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Center/Yale-New Haven Hospital
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital/Joe DiMaggio Children's Hospital
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute
    • Orlando, Florida, United States, 32806
      • Orlando Health Cancer Institute
    • Pembroke Pines, Florida, United States, 33028
      • Memorial Hospital West
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital/Winship Cancer Institute
    • Augusta, Georgia, United States, 30912
      • Augusta University Medical Center
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Pali Momi Medical Center
    • 'Aiea, Hawaii, United States, 96701
      • Queen's Cancer Center - Pearlridge
    • 'Aiea, Hawaii, United States, 96701
      • The Cancer Center of Hawaii-Pali Momi
    • 'Aiea, Hawaii, United States, 96701
      • Hawaii Cancer Care - Westridge
    • Hilo, Hawaii, United States, 96720
      • Island Urology-Hilo
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96817
      • The Cancer Center of Hawaii-Liliha
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Cancer Care Inc - Waterfront Plaza
    • Honolulu, Hawaii, United States, 96813
      • Queen's Cancer Cenrer - POB I
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Cancer Care Inc-Liliha
    • Honolulu, Hawaii, United States, 96817
      • Kuakini Medical Center
    • Honolulu, Hawaii, United States, 96817
      • Queen's Cancer Center - Kuakini
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
    • Honolulu, Hawaii, United States, 96813
      • Island Urology
    • Honolulu, Hawaii, United States, 96819
      • Kaiser Permanente Moanalua Medical Center
    • Lihue, Hawaii, United States, 96766
      • Wilcox Memorial Hospital and Kauai Medical Clinic
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
    • Boise, Idaho, United States, 83712
      • Saint Luke's Cancer Institute - Boise
    • Caldwell, Idaho, United States, 83605
      • Saint Alphonsus Cancer Care Center-Caldwell
    • Coeur d'Alene, Idaho, United States, 83814
      • Kootenai Health - Coeur d'Alene
    • Emmett, Idaho, United States, 83617
      • Walter Knox Memorial Hospital
    • Fruitland, Idaho, United States, 83619
      • Saint Luke's Cancer Institute - Fruitland
    • Meridian, Idaho, United States, 83642
      • Idaho Urologic Institute-Meridian
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Cancer Institute - Meridian
    • Nampa, Idaho, United States, 83686
      • Saint Luke's Cancer Institute - Nampa
    • Nampa, Idaho, United States, 83687
      • Saint Alphonsus Cancer Care Center-Nampa
    • Post Falls, Idaho, United States, 83854
      • Kootenai Clinic Cancer Services - Post Falls
    • Sandpoint, Idaho, United States, 83864
      • Kootenai Cancer Clinic
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Cancer Institute - Twin Falls
  • Illinois
    • Alton, Illinois, United States, 62002
      • Saint Anthony's Health
    • Burr Ridge, Illinois, United States, 60527
      • Loyola Center for Health at Burr Ridge
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago Comprehensive Cancer Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem-Evanston Hospital
    • Glenview, Illinois, United States, 60026
      • NorthShore University HealthSystem-Glenbrook Hospital
    • Highland Park, Illinois, United States, 60035
      • NorthShore University HealthSystem-Highland Park Hospital
    • Homer Glen, Illinois, United States, 60491
      • Loyola Medicine Homer Glen
    • Lake Forest, Illinois, United States, 60045
      • Northwestern Medicine Lake Forest Hospital
    • Lisle, Illinois, United States, 60532
      • Rush Cancer Care in Lisle
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Melrose Park, Illinois, United States, 60160
      • Marjorie Weinberg Cancer Center at Loyola-Gottlieb
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • New Lenox, Illinois, United States, 60451
      • UC Comprehensive Cancer Center at Silver Cross
    • Orland Park, Illinois, United States, 60462
      • University of Chicago Medicine-Orland Park
  • Iowa
    • Carroll, Iowa, United States, 51401
      • Saint Anthony Regional Hospital
    • Des Moines, Iowa, United States, 50309
      • Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50309
      • Blank Children's Hospital
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates-Des Moines
    • Des Moines, Iowa, United States, 50314
      • Broadlawns Medical Center
    • Des Moines, Iowa, United States, 50316
      • Iowa Lutheran Hospital
    • Fort Dodge, Iowa, United States, 50501
      • Trinity Regional Medical Center
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • West Des Moines, Iowa, United States, 50266-7700
      • Methodist West Hospital
  • Kansas
    • Garden City, Kansas, United States, 67846
      • Central Care Cancer Center - Garden City
    • Great Bend, Kansas, United States, 67530
      • Central Care Cancer Center - Great Bend
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Westwood, Kansas, United States, 66205
      • University of Kansas Hospital-Westwood Cancer Center
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas-Wichita Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas - Wichita
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Ochsner Health Center-Summa
    • Baton Rouge, Louisiana, United States, 70816
      • Medical Center of Baton Rouge
    • Baton Rouge, Louisiana, United States, 70836
      • Ochsner High Grove
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center Jefferson
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Saint Joseph Mercy Hospital
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Brighton, Michigan, United States, 48114
      • Saint Joseph Mercy Brighton
    • Brighton, Michigan, United States, 48114
      • Trinity Health IHA Medical Group Hematology Oncology - Brighton
    • Canton, Michigan, United States, 48188
      • Saint Joseph Mercy Canton
    • Canton, Michigan, United States, 48188
      • Trinity Health IHA Medical Group Hematology Oncology - Canton
    • Caro, Michigan, United States, 48723
      • Caro Cancer Center
    • Chelsea, Michigan, United States, 48118
      • Saint Joseph Mercy Chelsea
    • Chelsea, Michigan, United States, 48118
      • Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
    • Clarkston, Michigan, United States, 48346
      • Hematology Oncology Consultants-Clarkston
    • Clarkston, Michigan, United States, 48346
      • Newland Medical Associates-Clarkston
    • Detroit, Michigan, United States, 48201
      • Wayne State University/Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48236
      • Ascension Saint John Hospital
    • East China Township, Michigan, United States, 48054
      • Great Lakes Cancer Management Specialists-Doctors Park
    • Farmington Hills, Michigan, United States, 48334
      • Weisberg Cancer Treatment Center
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesee Cancer and Blood Disease Treatment Center
    • Flint, Michigan, United States, 48503
      • Genesee Hematology Oncology PC
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Helen DeVos Children's Hospital at Spectrum Health
    • Grand Rapids, Michigan, United States, 49503
      • Trinity Health Grand Rapids Hospital
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Academic Hematology Oncology Specialists
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Great Lakes Cancer Management Specialists-Van Elslander Cancer Center
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Michigan Breast Specialists-Grosse Pointe Woods
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Medical Center
    • Kalamazoo, Michigan, United States, 49009
      • Ascension Borgess Cancer Center
    • Lansing, Michigan, United States, 48912
      • University of Michigan Health - Sparrow Lansing
    • Livonia, Michigan, United States, 48154
      • Trinity Health Saint Mary Mercy Livonia Hospital
    • Livonia, Michigan, United States, 48154
      • Hope Cancer Clinic
    • Macomb, Michigan, United States, 48044
      • Great Lakes Cancer Management Specialists-Macomb Medical Campus
    • Macomb, Michigan, United States, 48044
      • Michigan Breast Specialists-Macomb Township
    • Marlette, Michigan, United States, 48453
      • Saint Mary's Oncology/Hematology Associates of Marlette
    • Muskegon, Michigan, United States, 49444
      • Trinity Health Muskegon Hospital
    • Niles, Michigan, United States, 49120
      • Corewell Health Lakeland Hospitals - Niles Hospital
    • Norton Shores, Michigan, United States, 49444
      • Cancer and Hematology Centers of Western Michigan - Norton Shores
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Pontiac, Michigan, United States, 48341
      • 21st Century Oncology-Pontiac
    • Pontiac, Michigan, United States, 48341
      • Hope Cancer Center
    • Pontiac, Michigan, United States, 48341
      • Newland Medical Associates-Pontiac
    • Reed City, Michigan, United States, 49677
      • Corewell Health Reed City Hospital
    • Rochester Hills, Michigan, United States, 48309
      • Great Lakes Cancer Management Specialists-Rochester Hills
    • Saginaw, Michigan, United States, 48601
      • Ascension Saint Mary's Hospital
    • Saginaw, Michigan, United States, 48604
      • Oncology Hematology Associates of Saginaw Valley PC
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center Saint Joseph
    • Saint Joseph, Michigan, United States, 49085
      • Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
    • Sterling Heights, Michigan, United States, 48312
      • Bhadresh Nayak MD PC-Sterling Heights
    • Tawas City, Michigan, United States, 48764
      • Ascension Saint Joseph Hospital
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Warren, Michigan, United States, 48093
      • Saint John Macomb-Oakland Hospital
    • Warren, Michigan, United States, 48088
      • Advanced Breast Care Center PLLC
    • Warren, Michigan, United States, 48093
      • Great Lakes Cancer Management Specialists-Macomb Professional Building
    • Warren, Michigan, United States, 48093
      • Macomb Hematology Oncology PC
    • Warren, Michigan, United States, 48093
      • Michigan Breast Specialists-Warren
    • West Branch, Michigan, United States, 48661
      • Saint Mary's Oncology/Hematology Associates of West Branch
    • Wyoming, Michigan, United States, 49519
      • University of Michigan Health - West
    • Ypsilanti, Michigan, United States, 48197
      • Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
    • Ypsilanti, Michigan, United States, 48106
      • Huron Gastroenterology PC
  • Minnesota
    • Aitkin, Minnesota, United States, 56431
      • Riverwood Healthcare Center
    • Brainerd, Minnesota, United States, 56401
      • Essentia Health Saint Joseph's Medical Center
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Burnsville, Minnesota, United States, 55337
      • Minnesota Oncology - Burnsville
    • Cambridge, Minnesota, United States, 55008
      • Cambridge Medical Center
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Deer River, Minnesota, United States, 56636
      • Essentia Health - Deer River Clinic
    • Detroit Lakes, Minnesota, United States, 56501
      • Essentia Health Saint Mary's - Detroit Lakes Clinic
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Cancer Center
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Saint Mary's Medical Center
    • Duluth, Minnesota, United States, 55805
      • Miller-Dwan Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fergus Falls, Minnesota, United States, 56537
      • Lake Region Healthcare Corporation-Cancer Care
    • Fosston, Minnesota, United States, 56542
      • Essentia Health - Fosston
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Hibbing, Minnesota, United States, 55746
      • Essentia Health Hibbing Clinic
    • Maple Grove, Minnesota, United States, 55369
      • Fairview Clinics and Surgery Center Maple Grove
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55454
      • Health Partners Inc
    • Monticello, Minnesota, United States, 55362
      • Monticello Cancer Center
    • New Ulm, Minnesota, United States, 56073
      • New Ulm Medical Center
    • Park Rapids, Minnesota, United States, 56470
      • Essentia Health - Park Rapids
    • Princeton, Minnesota, United States, 55371
      • Fairview Northland Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Sandstone, Minnesota, United States, 55072
      • Essentia Health Sandstone
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Virginia, Minnesota, United States, 55792
      • Essentia Health Virginia Clinic
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
    • Wyoming, Minnesota, United States, 55092
      • Fairview Lakes Medical Center
  • Missouri
    • Ballwin, Missouri, United States, 63011
      • Saint Louis Cancer and Breast Institute-Ballwin
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center - Bolivar
    • Branson, Missouri, United States, 65616
      • Cox Cancer Center Branson
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Joplin, Missouri, United States, 64804
      • Mercy Hospital Joplin
    • Rolla, Missouri, United States, 65401
      • Delbert Day Cancer Institute at PCRMC
    • Rolla, Missouri, United States, 65401
      • Mercy Clinic-Rolla-Cancer and Hematology
    • Saint Joseph, Missouri, United States, 64506
      • Heartland Regional Medical Center
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63128
      • Mercy Hospital South
    • Saint Louis, Missouri, United States, 63129
      • Siteman Cancer Center-South County
    • Saint Louis, Missouri, United States, 63109
      • Saint Louis Cancer and Breast Institute-South City
    • Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Saint Peters Hospital
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
    • Washington, Missouri, United States, 63090
      • Mercy Hospital Washington
  • Montana
    • Anaconda, Montana, United States, 59711
      • Community Hospital of Anaconda
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Billings, Montana, United States, 59101
      • Saint Vincent Healthcare
    • Billings, Montana, United States, 59102
      • Saint Vincent Frontier Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Butte, Montana, United States, 59701
      • Saint James Community Hospital and Cancer Treatment Center
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic
    • Great Falls, Montana, United States, 59405
      • Benefis Healthcare- Sletten Cancer Institute
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Missoula, Montana, United States, 59804
      • Community Medical Hospital
    • Missoula, Montana, United States, 59802
      • Saint Patrick Hospital - Community Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68118
      • Nebraska Medicine-Village Pointe
  • Nevada
    • Carson City, Nevada, United States, 89703
      • Carson Tahoe Regional Medical Center
    • Henderson, Nevada, United States, 89052
      • Comprehensive Cancer Centers of Nevada - Henderson
    • Henderson, Nevada, United States, 89052
      • OptumCare Cancer Care at Seven Hills
    • Henderson, Nevada, United States, 89052
      • Cancer and Blood Specialists-Henderson
    • Henderson, Nevada, United States, 89052
      • Las Vegas Cancer Center-Henderson
    • Henderson, Nevada, United States, 89074
      • Comprehensive Cancer Centers of Nevada-Southeast Henderson
    • Henderson, Nevada, United States, 89074
      • GenesisCare USA - Henderson
    • Henderson, Nevada, United States, 89052
      • Comprehensive Cancer Centers of Nevada-Horizon Ridge
    • Henderson, Nevada, United States, 89074
      • Las Vegas Urology - Green Valley
    • Henderson, Nevada, United States, 89074
      • Las Vegas Urology - Pebble
    • Henderson, Nevada, United States, 89074
      • Urology Specialists of Nevada - Green Valley
    • Las Vegas, Nevada, United States, 89144
      • Summerlin Hospital Medical Center
    • Las Vegas, Nevada, United States, 89109
      • Sunrise Hospital and Medical Center
    • Las Vegas, Nevada, United States, 89102
      • OptumCare Cancer Care at Charleston
    • Las Vegas, Nevada, United States, 89106
      • Radiation Oncology Centers of Nevada Central
    • Las Vegas, Nevada, United States, 89109
      • GenesisCare USA - Las Vegas
    • Las Vegas, Nevada, United States, 89119
      • Radiation Oncology Centers of Nevada Southeast
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers of Nevada - Northwest
    • Las Vegas, Nevada, United States, 89128
      • OptumCare Cancer Care at MountainView
    • Las Vegas, Nevada, United States, 89135
      • Alliance for Childhood Diseases/Cure 4 the Kids Foundation
    • Las Vegas, Nevada, United States, 89144
      • Comprehensive Cancer Centers of Nevada - Town Center
    • Las Vegas, Nevada, United States, 89144
      • Comprehensive Cancer Centers of Nevada-Summerlin
    • Las Vegas, Nevada, United States, 89148
      • Comprehensive Cancer Centers of Nevada
    • Las Vegas, Nevada, United States, 89148
      • OptumCare Cancer Care at Fort Apache
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada - Central Valley
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89128
      • GenesisCare USA - Vegas Tenaya
    • Las Vegas, Nevada, United States, 89148-2405
      • Las Vegas Cancer Center-Medical Center
    • Las Vegas, Nevada, United States, 89148
      • GenesisCare USA - Fort Apache
    • Las Vegas, Nevada, United States, 89128
      • Ann M Wierman MD LTD
    • Las Vegas, Nevada, United States, 89074
      • Las Vegas Urology - Pecos
    • Las Vegas, Nevada, United States, 89102
      • Desert West Surgery
    • Las Vegas, Nevada, United States, 89103
      • Hope Cancer Care of Nevada
    • Las Vegas, Nevada, United States, 89106
      • Urology Specialists of Nevada - Central
    • Las Vegas, Nevada, United States, 89113
      • Las Vegas Prostate Cancer Center
    • Las Vegas, Nevada, United States, 89113
      • Las Vegas Urology - Sunset
    • Las Vegas, Nevada, United States, 89128
      • Las Vegas Urology - Cathedral Rock
    • Las Vegas, Nevada, United States, 89128
      • Las Vegas Urology - Smoke Ranch
    • Las Vegas, Nevada, United States, 89128
      • Urology Specialists of Nevada - Northwest
    • Las Vegas, Nevada, United States, 89169
      • University Cancer Center
    • Las Vegas, Nevada, United States, 89113
      • Urology Specialists of Nevada - Southwest
    • Pahrump, Nevada, United States, 89048
      • Hope Cancer Care of Nevada-Pahrump
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
    • Reno, Nevada, United States, 89503
      • Saint Mary's Regional Medical Center
    • Reno, Nevada, United States, 89509
      • Radiation Oncology Associates
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Lake Success, New York, United States, 11042
      • Northwell Health/Center for Advanced Medicine
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New Hyde Park, New York, United States, 11040
      • Long Island Jewish Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • New York, New York, United States, 10065
      • NYP/Weill Cornell Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
    • Syracuse, New York, United States, 13210
      • State University of New York Upstate Medical University
    • Verona, New York, United States, 13478
      • Upstate Cancer Center at Verona
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Essentia Health Cancer Center-South University Clinic
    • Jamestown, North Dakota, United States, 58401
      • Essentia Health - Jamestown Clinic
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Cancer Center-UC Medical Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • West Chester, Ohio, United States, 45069
      • University of Cincinnati Cancer Center-West Chester
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73120
      • Mercy Hospital Oklahoma City
  • Oregon
    • Baker City, Oregon, United States, 97814
      • Saint Alphonsus Medical Center-Baker City
    • Bend, Oregon, United States, 97701
      • Saint Charles Health System
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Clackamas, Oregon, United States, 97015
      • Providence Cancer Institute Clackamas Clinic
    • Coos Bay, Oregon, United States, 97420
      • Bay Area Hospital
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Ontario, Oregon, United States, 97914
      • Saint Alphonsus Medical Center-Ontario
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
    • Redmond, Oregon, United States, 97756
      • Saint Charles Health System-Redmond
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital-Cedar Crest
    • Bethlehem, Pennsylvania, United States, 18017
      • Lehigh Valley Hospital - Muhlenberg
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Pocono Medical Center
    • Hazleton, Pennsylvania, United States, 18201
      • Lehigh Valley Hospital-Hazleton
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania/Abramson Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Cancer Institute (UPCI)
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
    • Providence, Rhode Island, United States, 02906
      • Miriam Hospital
  • South Carolina
    • Boiling Springs, South Carolina, United States, 29316
      • Prisma Health Cancer Institute - Spartanburg
    • Clinton, South Carolina, United States, 29325
      • Prisma Health Cancer Institute - Laurens
    • Columbia, South Carolina, United States, 29203
      • Prisma Health Richland Hospital
    • Easley, South Carolina, United States, 29640
      • Prisma Health Cancer Institute - Easley
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Faris
    • Greenville, South Carolina, United States, 29607
      • Saint Francis Cancer Center
    • Greenville, South Carolina, United States, 29615
      • Prisma Health Cancer Institute - Eastside
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Cancer Institute - Butternut
    • Greenville, South Carolina, United States, 29601
      • Saint Francis Hospital
    • Greenville, South Carolina, United States, 29605
      • BI-LO Charities Children's Cancer Center
    • Greenville, South Carolina, United States, 29605
      • Prisma Health Greenville Memorial Hospital
    • Greer, South Carolina, United States, 29650
      • Prisma Health Cancer Institute - Greer
    • Seneca, South Carolina, United States, 29672
      • Prisma Health Cancer Institute - Seneca
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Methodist Hospital
    • Lubbock, Texas, United States, 79410
      • Covenant Medical Center-Lakeside
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital / Huntsman Intermountain Cancer Center
    • Cedar City, Utah, United States, 84720
      • Sandra L Maxwell Cancer Center
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center
    • Riverton, Utah, United States, 84065
      • Riverton Hospital
    • Saint George, Utah, United States, 84770
      • Saint George Regional Medical Center
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists-Salt Lake City
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University/Massey Cancer Center
  • Washington
    • Aberdeen, Washington, United States, 98520
      • Providence Regional Cancer System-Aberdeen
    • Bellevue, Washington, United States, 98004
      • Overlake Medical Center
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Centralia, Washington, United States, 98531
      • Providence Regional Cancer System-Centralia
    • Edmonds, Washington, United States, 98026
      • Swedish Cancer Institute-Edmonds
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership
    • Issaquah, Washington, United States, 98029
      • Swedish Cancer Institute-Issaquah
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Lacey, Washington, United States, 98503
      • Providence Regional Cancer System-Lacey
    • Longview, Washington, United States, 98632
      • PeaceHealth Saint John Medical Center
    • Port Townsend, Washington, United States, 98368
      • Jefferson Healthcare
    • Renton, Washington, United States, 98055
      • Valley Medical Center
    • Seattle, Washington, United States, 98107
      • Swedish Medical Center-Ballard Campus
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98112
      • Kaiser Permanente Washington
    • Seattle, Washington, United States, 98104
      • Pacific Gynecology Specialists
    • Seattle, Washington, United States, 98122-5711
      • Swedish Medical Center-Cherry Hill
    • Sedro-Woolley, Washington, United States, 98284
      • PeaceHealth United General Medical Center
    • Shelton, Washington, United States, 98584
      • Providence Regional Cancer System-Shelton
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
    • Walla Walla, Washington, United States, 99362
      • Providence Saint Mary Regional Cancer Center
    • Yakima, Washington, United States, 98902
      • North Star Lodge Cancer Center at Yakima Valley Memorial Hospital
    • Yelm, Washington, United States, 98597
      • Providence Regional Cancer System-Yelm
  • Wisconsin
    • Ashland, Wisconsin, United States, 54806
      • Duluth Clinic Ashland
    • Ashland, Wisconsin, United States, 54806
      • Northwest Wisconsin Cancer Center
    • Hayward, Wisconsin, United States, 54843
      • Essentia Health-Hayward Clinic
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center-Marshfield
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin
    • Spooner, Wisconsin, United States, 54801
      • Essentia Health-Spooner Clinic
    • Superior, Wisconsin, United States, 54880
      • Essentia Health Saint Mary's Hospital - Superior
  • Wyoming
    • Cheyenne, Wyoming, United States, 82001
      • Cheyenne Regional Medical Center-West
    • Cody, Wyoming, United States, 82414
      • Billings Clinic-Cody
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 39 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

REGISTRATION ELIGIBILITY CRITERIA (STEP 1)

• Newly diagnosed patients with CD-22 positive B-cell acute lymphoblastic leukemia (WHO criteria) are eligible. Patients with Burkitt type ALL are NOT eligible
• Patients who have BCR-ABL fusion transcript determined by fluorescence in situ hybridization (FISH) or real time-polymerase chain reaction (RT-PCR) or t(9;22)(q34;q11) by cytogenetics are not eligible and should be considered for enrollment on studies that incorporate imatinib during induction; please note: flow cytometry is to be performed at the local reference lab and must include assessment of CD20 and CD22 positivity, as well as CD29 and CD22 anti-positivity
• No prior therapy except for limited treatment (< 7 days) with corticosteroids or hydroxyurea and a single dose of intrathecal cytarabine
• No prior therapy for acute leukemia except emergency therapy (corticosteroids or hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration of the kidneys; when indicated, leukapheresis or exchange transfusion is recommended to reduce the WBC
• Single-dose intrathecal cytarabine is allowed prior to registration or prior to initiation of systematic therapy for patient convenience; systemic chemotherapy must begin within 72 hours of this intrathecal therapy
• Patients receiving prior steroid therapy are eligible for study; the dose and duration of previous steroid therapy should be carefully documented on case report forms
• Not pregnant and not nursing; for women of childbearing potential only, a negative urine or serum pregnancy test done =< 7 days prior to registration is required
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patients with down syndrome are excluded from this study
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN), unless suspected leukemic involvement of the liver
• Direct bilirubin =< 3 x upper limit of normal (ULN), unless suspected leukemic involvement of the liver
• Calculated (calc.) creatinine clearance >= 50 mL/min by Cockcroft-Gault

RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2)

• Completion of remission induction therapy

• Patients with M2 marrow or better are eligible; patients with M3 or M4 marrow (greater than 25% lymphoblasts) will not be eligible to be randomized

  • Rating: M0, M1; Blast Cells (%): 0-5.0
  • Rating: M2; Blast Cells (%): 5.1-25.0
  • Rating: M3; Blast Cells (%): > 25-50
  • Rating: M4; Blast Cells (%): > 50.0
  • The term "blast cell" includes any cell that cannot be classified as a more mature normal element, and includes "leukemic cells," pathologic lymphocytes, and stem cells
• No ascites, effusions or significant edema
• Absolute neutrophil count (ANC) >= 1,000/mm^3
• Platelet count >= 100,000/mm^3
• Total bilirubin =< 1.5 x upper limit of normal (ULN), except for patients with known Gilbert's syndrome
• Aspartate aminotransferase (AST) =< 8 x upper limit of normal (ULN)
• Completion of first 12 weeks (12+ weeks) of maintenance therapy (Course V)
• Patient has at least 24 weeks (24+ weeks) remaining before end of maintenance therapy (Course V)
• Patient is in complete continuous first remission at entry into A041501-HO1
• Patient is receiving oral anti-metabolite chemotherapy during the maintenance phase of therapy; treatment plan must call for the following doses of antimetabolites: 6MP 75 mg/m2/day orally; methotrexate (MTX) 20 mg/m2/week orally (modification of 6 MP or MTX dosing based on laboratory or clinical parameters is acceptable)
• Patient is able and willing to use the Medication Event Monitoring System (MEMS) TrackCap (e.g. not using a pillbox)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (frontline chemotherapy); See detailed description.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Daunorubicin Hydrochloride; Given IV; Drug: Cyclophosphamide; Given IV; Drug: Mercaptopurine; Given PO; Drug: Vincristine Sulfate; Given IV; Drug: Dexamethasone; Given PO or IV; Drug: Thioguanine; Given PO; Biological: Rituximab; Given IV; Procedure: Bone Marrow Aspiration and Biopsy; Undergo bone marrow aspiration and biopsy; Drug: Allopurinol; Given PO; Drug: Cytarabine; Given IT, IV, SC; Drug: Pegylated L-Asparaginase; Given IV; Drug: Methotrexate; Given IT, IV, PO
Experimental: Arm II (frontline chemotherapy, inotuzumab ozogamicin); Patients receive inotuzumab ozogamicin IV on days 1, 8, and 15 and undergo bone marrow aspirate and biopsy on day 28. Treatment repeats every 28 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive remission consolidated chemotherapy, interim maintenance chemotherapy, delayed intensification, and maintenance therapy as in Arm I.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Daunorubicin Hydrochloride; Given IV; Drug: Cyclophosphamide; Given IV; Drug: Mercaptopurine; Given PO; Drug: Vincristine Sulfate; Given IV; Drug: Dexamethasone; Given PO or IV; Drug: Thioguanine; Given PO; Biological: Rituximab; Given IV; Drug: Doxorubicin; Given IV; Biological: Inotuzumab Ozogamicin; Given IV; Procedure: Bone Marrow Aspiration and Biopsy; Undergo bone marrow aspiration and biopsy; Drug: Allopurinol; Given PO; Drug: Cytarabine; Given IT, IV, SC; Drug: Pegylated L-Asparaginase; Given IV; Drug: Methotrexate; Given IT, IV, PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EFS	Will be compared using log-rank tests. EFS curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model. The corresponding hazard ratio, 2- and 3-year EFS estimates will be assessed, and EFS medians along with their 95% confidence intervals for the two treatment arms.	Time from induction response to the time of progressive-disease, secondary malignancy, or death, assessed up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFS		Time from achievement of CR to the time of relapse and/or death, assessed up to 10 years
OS	Will be evaluated using Kaplan-Meier as well as Cox regression models.	Time from randomization to the time of death due to any cause, assessed up to 10 years
Proportion of patients who achieve CR or any response to induction therapy	Will be summarized as the proportion of patients who achieve any type of response to induction therapy divided by the number of all evaluable patients registered to this trial and who received at least one dose of induction therapy. Corresponding 95% binomial confidence intervals will also be calculated.	Up to 10 years
Overall induction response rates	Will be summarized as the proportion of patients who achieve any type of response to induction therapy divided by the number of all evaluable patients registered to this trial and who received at least one dose of induction therapy. Corresponding 95% binomial confidence intervals will also be calculated.	Up to 10 years
Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4.0	The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, all adverse event data that is graded as 3, 4, or 5 will be reviewed and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The incidence of severe (grade 3+) adverse events or toxicities will be described for each treatment arm, but will also be compared between the arms. Fisher's exact tests will be used to quantitatively compare the incidence of severe as well as specific toxicities of interest between the treatment arms and we will graphically assess differences in maximum grades observed for toxicities between the arms. Tolerability of the treatment arms will be assessed through assessing the number of patients who required dose modifications and/or dose delays.	Up to 10 years
Proportion of patients who go off treatment due to adverse reactions	Will be assessed within each of the treatment arms and differences explores in these measures between the arms.	Up to 10 years
Proportion of patients who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial	Will be assessed within each of the treatment arms and differences explores in these measures between the arms.	Up to 10 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: daniel_deangelo@dfci.harvard.edu J. DeAngelo, MD, PhD, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• Seftel MD. Hyper-CVAD: a regimen for all seasons. Lancet Haematol. 2020 Jul;7(7):e501-e502. doi: 10.1016/S2352-3026(20)30179-4. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2017
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: May 9, 2017
• First Submitted That Met QC Criteria: May 10, 2017
• First Posted (Actual): May 12, 2017

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Dermatologic Agents; Antibiotics, Antineoplastic; Reproductive Control Agents; Antioxidants; Free Radical Scavengers; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Gout Suppressants; Immunoconjugates; Immunotoxins; Dexamethasone; Cyclophosphamide; Rituximab; Doxorubicin; Cytarabine; Methotrexate; Vincristine; Daunorubicin; Asparaginase; Mercaptopurine; Allopurinol; Thioguanine; Pegaspargase; Inotuzumab Ozogamicin
• Other Study ID Numbers: A041501; U10CA180821 (U.S. NIH Grant/Contract); NCI-2016-01981 (Registry Identifier: Clinical Trial Reporting Program)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No