- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05303792
Testing the Combination of Inotuzumab Ozogamicin and Lower Dose Chemotherapy Compared to Usual Chemotherapy for Adults With B-Cell Acute Lymphoblastic Leukemia or B-Cell Lymphoblastic Lymphoma
A Randomized Phase II Study Comparing Inotuzumab Plus Chemotherapy Versus Standard Chemotherapy in Older Adults With Philadelphia-Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia
Study Overview
Status
Detailed Description
PRIMARY OBJECTIVE:
I. To compare undetectable measurable residual disease (MRD) event-free survival (EFS) rate of the experimental arm (A) to standard arm (B) with EFS defined as time from randomization to occurrence of an event.
SECONDARY OBJECTIVES:
I. To determine overall response rate (complete response [CR], CR + complete remission with incomplete platelet counts [CRp], CR + complete remission with partial hematologic recovery [CRh], CR + complete remission with incomplete blood count recovery [CRi]) at designated time points (after cycle 1, after cycle 2, end of intensive phase) in each treatment arm.
II. To determine rate of flow cytometry MRD-negativity (undetectable or detectable < 10^-4) at designated time points (after cycle 1, after cycle 2, end of intensive phase) in each treatment arm.
III. To compare MRD response by central aspirate multiparameter flow cytometry (Wood lab) to next generation sequencing MRD assessment (clonoSEQ, Adaptive) of blood and bone marrow at designated time points (after cycle 1, after cycle 2, and end of intensive phase) and to determine association with outcome, in each treatment arm.
IV. To determine the event-free survival (EFS) standard-definition (event defined as failure to achieve morphologic remission by cycle 2, hematologic relapse, death), disease-free survival (DFS), overall survival (OS) of each arm (median, 6-month, 1-year, 2-year, 3-year) in each treatment arm.
V. To determine proportion of patients who proceed to allogeneic transplant after initial response (without intervening salvage therapy) in each treatment arm.
VI. To determine rate of liver toxicity (grade 3-5 alanine aminotransferase [ALT] increase, aspartate aminotransferase [AST] increase, bilirubin increase, alkaline phosphatase increase).
VII. To describe the safety and tolerability of each arm including rate of grade 3-5 non-hematologic toxicity and treatment-related mortality (grade 5 toxicity VIII. To determine rate of delays in intensive-phase chemotherapy due to neutropenia and thrombocytopenia (in responding patients).
IX. To assess the baseline variations in comorbidity burden, physical, nutritional, and cognitive function of the study participants, and explore the association between comorbidity burden, physical, nutritional, and cognitive function, and the outcomes of therapy (grade 3-5 non-hematological toxicities, and OS).
X. To explore the longitudinal changes in physical, nutritional, and cognitive function among the experimental and control groups.
XI. To compare the burden of patient-reported symptomatic adverse events between treatment arms using the Patient Reported Outcomes - Common Terminology Criteria for Adverse Events (PRO-CTCAE).
XII. To correlate specific karyotype groups (normal or various primary and secondary chromosomal abnormalities) with clinical and laboratory parameters.
XIII. To correlate specific karyotype groups with response rates, response duration, MRD, and survival in patients treated on this study.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A:
INDUCTION: Patients receive cyclophosphamide intravenously (IV) over 3 hours every 12 hours (Q12H) on days 1-3 of cycles 1, 3, 5, and 7, vincristine IV on days 1 and 8 of cycle 1, 3, 5, and 7, dexamethasone IV or orally (PO) on days 1-4 and 11-14 of cycles 1, 3, 5, and 7, inotuzumab ozogamicin IV over 1 hour on days 2 and 8 of cycles 1-4, methotrexate IV over 24 hours on day 1 of cycles 2, 4, 6, and 8, cytarabine IV over 3 hours Q12H on days 2-3 of cycles 2, 4, 6, and 8, and methylprednisolone IV over 2 hours Q12H on days 1-3. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For patients >= 70 years of age, treatment repeats every 28 days for 2 cycles (an additional 2 cycles may be given at the discretion of the principal investigator [PI]) in the absence of disease progression or unacceptable toxicity. For patients < 70 years of age, treatment repeats every 28 days for 8 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive vincristine IV on day 1, prednisone PO daily on days 1-5, mercaptopurine PO twice daily (BID) on days 1-28, and methotrexate PO weekly. Treatment repeats every 28 days for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
ARM B:
INDUCTION: Patients receive cyclophosphamide IV over 3 hours Q12H on days 1-3 of cycle 1, 3, 5, and 7, vincristine IV on days 1 and 8 of cycles 1, 3, 5, and 7, dexamethasone IV or PO on days 1-4 and 11-14 of cycle 1, 3, 5, and 7, doxorubicin IV over 24 hours on day 4 of cycles 1, 3, 5, and 7, methotrexate IV over 24 hours on day 1 of cycles 2, 4, 6, and 8, cytarabine IV over 3 hours Q12H on days 2-3 of cycles 2, 4, 6, and 8, and methylprednisolone IV over 2 hours Q12H on days 1-3 of cycles 2, 4, 6, and 8. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For patients >= 70 years of age, treatment repeats every 28 days for 2 cycles (an additional 2 cycles may be given at the discretion of the PI) in absence of disease progression or unacceptable toxicity. For patients < 70 years of age, treatment repeats every 28 days for 8 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive vincristine IV on day 1, prednisone PO daily on days 1-5, mercaptopurine PO BID on days 1-28, and methotrexate PO weekly. Treatment repeats every 28 days for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 2 months until 1 year after completion of therapy, every 3 months until 2 years after completion of therapy, and then every 6 months until 5 years from study registration.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Marlise R. Luskin, MD, MSCE
- Phone Number: 617-632-2168
- Email: marlise_luskin@dfci.harvard.edu
Study Locations
-
-
-
San Juan, Puerto Rico, 00936
- Recruiting
- San Juan City Hospital
-
Principal Investigator:
- Luis J. Santos Reyes
-
Contact:
- Site Public Contact
- Phone Number: 787-763-1296
-
-
-
-
Alabama
-
Birmingham, Alabama, United States, 35233
- Recruiting
- University of Alabama at Birmingham Cancer Center
-
Contact:
- Site Public Contact
- Phone Number: 205-934-0220
- Email: tmyrick@uab.edu
-
Principal Investigator:
- Sravanti Rangaraju
-
-
California
-
Palo Alto, California, United States, 94304
- Recruiting
- Stanford Cancer Institute Palo Alto
-
Principal Investigator:
- Michaela Liedtke
-
Contact:
- Site Public Contact
- Phone Number: 650-498-7061
- Email: ccto-office@stanford.edu
-
-
Connecticut
-
New Haven, Connecticut, United States, 06520
- Recruiting
- Yale University
-
Contact:
- Site Public Contact
- Phone Number: 203-785-5702
- Email: canceranswers@yale.edu
-
Principal Investigator:
- Lourdes M. Mendez
-
-
Idaho
-
Boise, Idaho, United States, 83706
- Recruiting
- Saint Alphonsus Cancer Care Center-Boise
-
Contact:
- Site Public Contact
- Phone Number: 734-712-3671
- Email: stephanie.couch@stjoeshealth.org
-
Principal Investigator:
- John M. Schallenkamp
-
Boise, Idaho, United States, 83712
- Suspended
- Saint Luke's Cancer Institute - Boise
-
Caldwell, Idaho, United States, 83605
- Recruiting
- Saint Alphonsus Cancer Care Center-Caldwell
-
Contact:
- Site Public Contact
- Phone Number: 734-712-3671
- Email: stephanie.couch@stjoeshealth.org
-
Principal Investigator:
- John M. Schallenkamp
-
Coeur d'Alene, Idaho, United States, 83814
- Recruiting
- Kootenai Health - Coeur d'Alene
-
Principal Investigator:
- John M. Schallenkamp
-
Contact:
- Site Public Contact
- Phone Number: 406-969-6060
- Email: mccinfo@mtcancer.org
-
Nampa, Idaho, United States, 83687
- Recruiting
- Saint Alphonsus Cancer Care Center-Nampa
-
Principal Investigator:
- John M. Schallenkamp
-
Contact:
- Site Public Contact
- Phone Number: 406-969-6060
- Email: mccinfo@mtcancer.org
-
Post Falls, Idaho, United States, 83854
- Recruiting
- Kootenai Clinic Cancer Services - Post Falls
-
Principal Investigator:
- John M. Schallenkamp
-
Contact:
- Site Public Contact
- Phone Number: 406-969-6060
- Email: mccinfo@mtcancer.org
-
Sandpoint, Idaho, United States, 83864
- Recruiting
- Kootenai Cancer Clinic
-
Principal Investigator:
- John M. Schallenkamp
-
Contact:
- Site Public Contact
- Phone Number: 406-969-6060
- Email: mccinfo@mtcancer.org
-
-
Illinois
-
Chicago, Illinois, United States, 60637
- Recruiting
- University of Chicago Comprehensive Cancer Center
-
Principal Investigator:
- Wendy Stock
-
Contact:
- Site Public Contact
- Phone Number: 773-702-8222
- Email: cancerclinicaltrials@bsd.uchicago.edu
-
Chicago, Illinois, United States, 60611
- Recruiting
- Northwestern University
-
Principal Investigator:
- Shira N. Dinner
-
Contact:
- Site Public Contact
- Phone Number: 312-695-1301
- Email: cancer@northwestern.edu
-
Evanston, Illinois, United States, 60201
- Recruiting
- NorthShore University HealthSystem-Evanston Hospital
-
Principal Investigator:
- Amy Y. Wang
-
Contact:
- Site Public Contact
- Phone Number: 847-570-2109
-
Glenview, Illinois, United States, 60026
- Recruiting
- NorthShore University HealthSystem-Glenbrook Hospital
-
Principal Investigator:
- Amy Y. Wang
-
Contact:
- Site Public Contact
- Phone Number: 847-570-2109
-
Highland Park, Illinois, United States, 60035
- Recruiting
- NorthShore University HealthSystem-Highland Park Hospital
-
Principal Investigator:
- Amy Y. Wang
-
Contact:
- Site Public Contact
- Phone Number: 847-570-2109
-
Maywood, Illinois, United States, 60153
- Recruiting
- Loyola University Medical Center
-
Principal Investigator:
- Stephanie B. Tsai
-
Contact:
- Site Public Contact
- Phone Number: 708-226-4357
-
New Lenox, Illinois, United States, 60451
- Recruiting
- UC Comprehensive Cancer Center at Silver Cross
-
Principal Investigator:
- Wendy Stock
-
Contact:
- Site Public Contact
- Phone Number: 773-702-8222
- Email: cancerclinicaltrials@bsd.uchicago.edu
-
Orland Park, Illinois, United States, 60462
- Recruiting
- University of Chicago Medicine-Orland Park
-
Principal Investigator:
- Wendy Stock
-
Contact:
- Site Public Contact
- Phone Number: 773-702-8222
- Email: cancerclinicaltrials@bsd.uchicago.edu
-
Shiloh, Illinois, United States, 62269
- Recruiting
- Memorial Hospital East
-
Contact:
- Site Public Contact
- Phone Number: 314-747-9912
- Email: dschwab@wustl.edu
-
Principal Investigator:
- Ramzi Abboud
-
-
Kansas
-
Kansas City, Kansas, United States, 66160
- Recruiting
- University of Kansas Cancer Center
-
Principal Investigator:
- Kenneth Byrd
-
Contact:
- Site Public Contact
- Phone Number: 913-588-3671
- Email: KUCC_Navigation@kumc.edu
-
Westwood, Kansas, United States, 66205
- Recruiting
- University of Kansas Hospital-Westwood Cancer Center
-
Principal Investigator:
- Kenneth Byrd
-
Contact:
- Site Public Contact
- Phone Number: 913-588-3671
- Email: KUCC_Navigation@kumc.edu
-
-
Kentucky
-
Louisville, Kentucky, United States, 40207
- Recruiting
- Norton Suburban Hospital and Medical Campus
-
Contact:
- Site Public Contact
- Phone Number: 502-629-3465
-
Principal Investigator:
- Don A. Stevens
-
-
Mississippi
-
Southhaven, Mississippi, United States, 38671
- Recruiting
- Baptist Memorial Hospital and Cancer Center-Desoto
-
Principal Investigator:
- Salil Goorha
-
Contact:
- Site Public Contact
- Phone Number: 901-226-1366
- Email: BCCclintrials@bmhcc.org
-
-
Missouri
-
Creve Coeur, Missouri, United States, 63141
- Recruiting
- Siteman Cancer Center at West County Hospital
-
Contact:
- Site Public Contact
- Phone Number: 800-600-3606
- Email: info@siteman.wustl.edu
-
Principal Investigator:
- Ramzi Abboud
-
Saint Louis, Missouri, United States, 63110
- Recruiting
- Washington University School of Medicine
-
Contact:
- Site Public Contact
- Phone Number: 800-600-3606
- Email: info@siteman.wustl.edu
-
Principal Investigator:
- Ramzi Abboud
-
Saint Louis, Missouri, United States, 63129
- Recruiting
- Siteman Cancer Center-South County
-
Contact:
- Site Public Contact
- Phone Number: 800-600-3606
- Email: info@siteman.wustl.edu
-
Principal Investigator:
- Ramzi Abboud
-
Saint Louis, Missouri, United States, 63136
- Recruiting
- Siteman Cancer Center at Christian Hospital
-
Contact:
- Site Public Contact
- Phone Number: 800-600-3606
- Email: info@siteman.wustl.edu
-
Principal Investigator:
- Ramzi Abboud
-
Saint Peters, Missouri, United States, 63376
- Recruiting
- Siteman Cancer Center at Saint Peters Hospital
-
Contact:
- Site Public Contact
- Phone Number: 800-600-3606
- Email: info@siteman.wustl.edu
-
Principal Investigator:
- Ramzi Abboud
-
-
Montana
-
Anaconda, Montana, United States, 59711
- Recruiting
- Community Hospital of Anaconda
-
Principal Investigator:
- John M. Schallenkamp
-
Contact:
- Site Public Contact
- Phone Number: 406-969-6060
- Email: mccinfo@mtcancer.org
-
Billings, Montana, United States, 59101
- Recruiting
- Billings Clinic Cancer Center
-
Principal Investigator:
- John M. Schallenkamp
-
Contact:
- Site Public Contact
- Phone Number: 800-996-2663
- Email: research@billingsclinic.org
-
Bozeman, Montana, United States, 59715
- Recruiting
- Bozeman Deaconess Hospital
-
Principal Investigator:
- John M. Schallenkamp
-
Contact:
- Site Public Contact
- Phone Number: 406-969-6060
- Email: mccinfo@mtcancer.org
-
Great Falls, Montana, United States, 59405
- Recruiting
- Benefis Healthcare- Sletten Cancer Institute
-
Principal Investigator:
- John M. Schallenkamp
-
Contact:
- Site Public Contact
- Phone Number: 406-969-6060
- Email: mccinfo@mtcancer.org
-
Missoula, Montana, United States, 59804
- Recruiting
- Community Medical Hospital
-
Principal Investigator:
- John M. Schallenkamp
-
Contact:
- Site Public Contact
- Phone Number: 406-969-6060
- Email: mccinfo@mtcancer.org
-
-
Nebraska
-
Bellevue, Nebraska, United States, 68123
- Recruiting
- Nebraska Medicine-Bellevue
-
Principal Investigator:
- Vijaya R. Bhatt
-
Contact:
- Site Public Contact
- Phone Number: 402-559-6941
- Email: unmcrsa@unmc.edu
-
Omaha, Nebraska, United States, 68198
- Recruiting
- University of Nebraska Medical Center
-
Principal Investigator:
- Vijaya R. Bhatt
-
Contact:
- Site Public Contact
- Phone Number: 402-559-6941
- Email: unmcrsa@unmc.edu
-
Omaha, Nebraska, United States, 68118
- Recruiting
- Nebraska Medicine-Village Pointe
-
Principal Investigator:
- Vijaya R. Bhatt
-
Contact:
- Site Public Contact
- Phone Number: 402-559-5600
-
-
New York
-
Lake Success, New York, United States, 11042
- Recruiting
- Northwell Health/Center for Advanced Medicine
-
Contact:
- Site Public Contact
- Phone Number: 516-734-8896
-
Principal Investigator:
- Bradley H. Goldberg
-
Manhasset, New York, United States, 11030
- Recruiting
- North Shore University Hospital
-
Contact:
- Site Public Contact
- Phone Number: 516-734-8896
-
Principal Investigator:
- Bradley H. Goldberg
-
New York, New York, United States, 10029
- Recruiting
- Mount Sinai Hospital
-
Contact:
- Site Public Contact
- Phone Number: 212-824-7309
- Email: CCTO@mssm.edu
-
Principal Investigator:
- Jonathan Feld
-
Rochester, New York, United States, 14642
- Recruiting
- University of Rochester
-
Contact:
- Site Public Contact
- Phone Number: 585-275-5830
-
Principal Investigator:
- Paul M. Barr
-
-
Ohio
-
Columbus, Ohio, United States, 43210
- Recruiting
- Ohio State University Comprehensive Cancer Center
-
Principal Investigator:
- Gregory K. Behbehani
-
Contact:
- Site Public Contact
- Phone Number: 800-293-5066
- Email: Jamesline@osumc.edu
-
-
Oklahoma
-
Oklahoma City, Oklahoma, United States, 73104
- Recruiting
- University of Oklahoma Health Sciences Center
-
Contact:
- Site Public Contact
- Phone Number: 405-271-8777
- Email: ou-clinical-trials@ouhsc.edu
-
Principal Investigator:
- Mohamad Khawandanah
-
-
Oregon
-
Ontario, Oregon, United States, 97914
- Recruiting
- Saint Alphonsus Medical Center-Ontario
-
Principal Investigator:
- John M. Schallenkamp
-
Contact:
- Site Public Contact
- Phone Number: 406-969-6060
- Email: mccinfo@mtcancer.org
-
Portland, Oregon, United States, 97213
- Recruiting
- Providence Portland Medical Center
-
Principal Investigator:
- Alison K. Conlin
-
Contact:
- Site Public Contact
- Phone Number: 503-215-2614
- Email: CanRsrchStudies@providence.org
-
Portland, Oregon, United States, 97225
- Recruiting
- Providence Saint Vincent Medical Center
-
Principal Investigator:
- Alison K. Conlin
-
Contact:
- Site Public Contact
- Phone Number: 503-215-2614
- Email: CanRsrchStudies@providence.org
-
-
Pennsylvania
-
Danville, Pennsylvania, United States, 17822
- Recruiting
- Geisinger Medical Center
-
Contact:
- Site Public Contact
- Phone Number: 570-271-5251
- Email: HemonCCTrials@geisinger.edu
-
Principal Investigator:
- Joseph J. Vadakara
-
Philadelphia, Pennsylvania, United States, 19107
- Recruiting
- Thomas Jefferson University Hospital
-
Principal Investigator:
- Lindsay Wilde
-
Contact:
- Site Public Contact
- Phone Number: 215-600-9151
- Email: ONCTrialNow@jefferson.edu
-
Wilkes-Barre, Pennsylvania, United States, 18711
- Recruiting
- Geisinger Wyoming Valley/Henry Cancer Center
-
Contact:
- Site Public Contact
- Phone Number: 570-271-5251
- Email: HemonCCTrials@geisinger.edu
-
Principal Investigator:
- Joseph J. Vadakara
-
-
South Carolina
-
Charleston, South Carolina, United States, 29425
- Recruiting
- Medical University of South Carolina
-
Contact:
- Site Public Contact
- Phone Number: 843-792-9321
- Email: hcc-clinical-trials@musc.edu
-
Principal Investigator:
- Alexander Coltoff
-
-
Tennessee
-
Memphis, Tennessee, United States, 38120
- Recruiting
- Baptist Memorial Hospital and Cancer Center-Memphis
-
Principal Investigator:
- Salil Goorha
-
Contact:
- Site Public Contact
- Phone Number: 901-226-1366
- Email: BCCclintrials@bmhcc.org
-
-
Vermont
-
Burlington, Vermont, United States, 05401
- Recruiting
- University of Vermont Medical Center
-
Contact:
- Site Public Contact
- Phone Number: 802-656-4101
- Email: rpo@uvm.edu
-
Principal Investigator:
- Diego A. Adrianzen Herrera
-
-
Virginia
-
Richmond, Virginia, United States, 23298
- Recruiting
- Virginia Commonwealth University/Massey Cancer Center
-
Principal Investigator:
- Keri R. Maher
-
Contact:
- Site Public Contact
- Email: CTOclinops@vcu.edu
-
-
West Virginia
-
Morgantown, West Virginia, United States, 26506
- Recruiting
- West Virginia University Healthcare
-
Contact:
- Site Public Contact
- Phone Number: 304-293-7374
- Email: cancertrialsinfo@hsc.wvu.edu
-
Principal Investigator:
- Konstantinos Sdrimas
-
-
Wisconsin
-
Eau Claire, Wisconsin, United States, 54701
- Recruiting
- Marshfield Medical Center-EC Cancer Center
-
Contact:
- Site Public Contact
- Phone Number: 800-782-8581
- Email: oncology.clinical.trials@marshfieldresearch.org
-
Principal Investigator:
- Chady A. Leon
-
La Crosse, Wisconsin, United States, 54601
- Recruiting
- Gundersen Lutheran Medical Center
-
Contact:
- Site Public Contact
- Phone Number: 608-775-2385
- Email: cancerctr@gundersenhealth.org
-
Principal Investigator:
- Michael O. Ojelabi
-
Milwaukee, Wisconsin, United States, 53226
- Recruiting
- Medical College of Wisconsin
-
Contact:
- Site Public Contact
- Phone Number: 414-805-3666
-
Principal Investigator:
- Guru Subramanian Guru Murthy
-
Minocqua, Wisconsin, United States, 54548
- Recruiting
- Marshfield Clinic-Minocqua Center
-
Contact:
- Site Public Contact
- Phone Number: 800-782-8581
- Email: oncology.clinical.trials@marshfieldresearch.org
-
Principal Investigator:
- Chady A. Leon
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- PRE-REGISTRATION ELIGIBILITY CRITERIA (STEP 0)
Research bone marrow or peripheral blood submission
* This bone marrow or peripheral blood submission is mandatory prior to registration/randomization as baseline for real-time MRD analysis. The bone marrow sample should be from the first aspiration (i.e., first pull). Aspirate needle should be redirected if needed to get first pull bone marrow aspirate. It should be obtained as soon after pre-registration as possible
- REGISTRATION INCLUSION CRITERIA (STEP 1)
Diagnosis of B-cell acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) per World Health Organization (WHO) 2016 criteria. Patients must have >= 5% blasts in the bone marrow or blood. Patients with lymphoblastic lymphoma (LBL) without measurable marrow involvement (>= 5% blasts) are not eligible
* T-cell ALL/LBL, Philadelphia-chromosome positive B-cell (as determined by fluorescence in situ hybridization [FISH], cytogenetics, or reverse transcriptase polymerase chain reaction [RT-PCR]), and Burkitt's like leukemia/lymphoma (mature B-ALL) are not eligible
- Must be CD22 positive by local assessment (>= 20% by immunohistochemistry or flow cytometry). Patients are eligible regardless of CD20 status but CD20 expression should be assessed at diagnosis by flow cytometry or immunohistochemistry
- Patients must have >= 5% blasts in the bone marrow or blood. Patients with lymphoblastic lymphoma (LBL) without marrow involvement (>= 5% blasts) are not eligible
- No prior chemotherapy for ALL except for hydroxyurea (no limit), steroids limited to 7 days, ATRA (no limit), vincristine (single dose), and/or intra-thecal chemotherapy. Leukapheresis is permitted. Palliative radiation to doses 24 Gy or less is permitted. Patients being treated with chronic steroids for other reasons (autoimmune disorder, etc.) are eligible
- Age >= 50 years
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2. ECOG 3 permitted if related to disease
- Creatinine =< 2.0 g/dL
Total bilirubin =< 1.5 x upper limit of normal (ULN)
* Except in the event of: 1) Gilbert disease, in which case total bilirubin must be =< 2 x ULN, or 2) elevated bilirubin believed by investigator to be due to leukemic infiltration, in which case total bilirubin must be =< 2 x ULN
- AST / ALT =< 2.5 x upper limit of normal (ULN)
- Cardiac ejection fraction (as measured by multigated acquisition scan [MUGA] or echocardiogram) > 40%
No clinically relevant liver disease (such as cirrhosis, active hepatitis, or alcohol use disorder), which in the opinion of the treating physician would make this protocol unreasonably hazardous
- Patients with known hepatitis B virus (HBV) infection are eligible if they are on effective HBV suppressive therapy with undetectable HBV viral load and there is no clinically relevant liver disease present (related or unrelated to HBV-related liver damage)
- Patients with known history of hepatitis C virus (HCV) infection are eligible if they have cleared the infection spontaneously or via eradication therapy (HCV viral load undetectable) and there is no clinically relevant liver disease present (related or unrelated to HCV-related liver damage)
- Women and men of reproductive potential should agree to use an appropriate method of birth control throughout their participation in this study due to the teratogenic potential of the therapy utilized in this trial. Include as applicable: Appropriate methods of birth control include abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom)
Exclusion Criteria:
Physicians should consider whether any of the following may render the patient inappropriate for this protocol:
- Medical condition such as uncontrolled diabetes mellitus, uncontrolled cardiac disease, and uncontrolled pulmonary disease.
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- Patients with a "currently active" second malignancy other than non-melanoma skin cancers, early stage prostate cancer, cervical carcinoma in situ, or other cancer for which standard of care would be observation (not requiring treatment). Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for >= 1 year, or if the cancer has been surgically resected and considered cured. Patients with a history of multiple myeloma with absence of serum paraprotein for >= 1 year are not considered to have a "currently active" malignancy.
- REGISTRATION EXCLUSION CRITERIA (STEP 1)
- Patients with symptomatic central nervous system (CNS) disease are not eligible. CNS assessment is not required for eligibility determination if asymptomatic
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A (inotuzumab ozogamicin, chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive inotuzumab ozogamicin IV and IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment. Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity. |
Given IV
Given IV
Given PO
Given PO
Given IV
Given IV
Given IV
Given IV or PO
Given IV
Given IV or PO
|
Active Comparator: Arm B (chemotherapy)
Induction: For cycles 1-4 on days 2 and 8, patients receive IT chemotherapy consisting of alternating Cytarabine and Methotrexate. Patients with leukemic blasts expressing CD20 also receive rituximab IV on days 2 and 8 of cycles 1-4. For cycles 1,3,5,7, patients receive cyclophosphamide intravenously (IV) on days 1-3, mesna IV, doxorubicin IV on day 4, vincristine IV on days 1 and 8, and dexamethasone IV or orally (PO) on days 1-4 and 11-14. For cycles 2,4,6,8, patients receive methotrexate on day 1, cytarabine IV on days 2-3, and methylprednisolone on days 1-3. Patients >= 70 years of age receive either 2 or 4 cycles of treatment. Patients < 70 years of age receive up to 8 cycles of treatment. Maintenance: Patients receive vincristine IV on day 1, prednisone PO on days 1-5, mercaptopurine PO on days 1-28, and methotrexate PO weekly. Treatment occurs for up to 24 cycles or 2 years, whichever comes first, in the absence of disease progression or unacceptable toxicity. |
Given IV
Given IV
Given PO
Given PO
Given IV
Given IV
Given IV
Given IV or PO
Given IV
Given IV or PO
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Event-free survival
Time Frame: From randomization to failure to achieve measurable residual disease (MRD)-negative complete response (CR) after two cycles of chemotherapy, relapse, or death from any causes, assessed at 2 months (after 2 cycles of treatment)
|
Will be evaluated using the methods of Kaplan-Meier as well as Cox regression models.
|
From randomization to failure to achieve measurable residual disease (MRD)-negative complete response (CR) after two cycles of chemotherapy, relapse, or death from any causes, assessed at 2 months (after 2 cycles of treatment)
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease-free survival
Time Frame: Time from achieving a CR/ complete remission with incomplete blood count recovery (CRi) to the time of relapse and/or death, assessed up to 5 years
|
Will be evaluated using the methods of Kaplan-Meier as well as Cox regression models.
|
Time from achieving a CR/ complete remission with incomplete blood count recovery (CRi) to the time of relapse and/or death, assessed up to 5 years
|
Overall survival
Time Frame: From randomization to the time of death due to any cause, assessed up to 5 years
|
Will be evaluated using the methods of Kaplan-Meier as well as Cox regression models.
|
From randomization to the time of death due to any cause, assessed up to 5 years
|
Complete remission rate
Time Frame: Up to 5 years
|
The proportion of patients who achieve complete remission 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.
In a similar manner, the investigators will also evaluate the overall induction response rates.
All evaluable patients will be used for this analysis.
|
Up to 5 years
|
Overall response rate
Time Frame: Up to 5 years
|
Overall response rate (CR/CRi, CR/complete remission with incomplete platelet counts [CRp], CR/complete remission with partial hematologic recovery [CRh]).
The proportion of patients who achieve complete remission 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.
In a similar manner, the investigators will also evaluate the overall induction response rates.
All evaluable patients will be used for this analysis.
|
Up to 5 years
|
MRD-negativity rate
Time Frame: Up to end of cycle 8 (1 cycle = 28 days)
|
MRD-negativity by flow cytometry will be evaluated at designated time point (after cycle 1, after cycle 2, end of intensive phase).
Will also compare MRD assessment by centralized aspirate flow cytometry (Wood lab) to next generation sequencing (clonoSEQ, Adaptive) of blood and bone marrow at designated time points; and determine association with outcome.
|
Up to end of cycle 8 (1 cycle = 28 days)
|
Event-free survival
Time Frame: Up to 5 years
|
Event defined as failure to achieve Complete Response (CR)/Complete Remission with Incomplete Blood Count Recovery (CRi)/Complete Remission with Partial Hematological Recovery (CRh)/Complete Remission with Incomplete Platelet Counts (CRp), relapse, death.
|
Up to 5 years
|
Rate of grade 3-5 adverse events
Time Frame: Up to 5 years
|
The proportion of patients experiencing a grade 3+ adverse events or toxicities will be described for each treatment arm, but will also be compared between the arms using Fisher's exact tests.
|
Up to 5 years
|
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Marlise R. Luskin, MD, MSCE, Dana-Farber Cancer Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
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
- Lymphoma
- Leukemia
- Lymphoma, Non-Hodgkin
- 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
- Neuroprotective Agents
- 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
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Folic Acid Antagonists
- Immunoconjugates
- Immunotoxins
- Dexamethasone
- Methylprednisolone
- Cyclophosphamide
- Rituximab
- Prednisone
- Doxorubicin
- Cytarabine
- Methotrexate
- Vincristine
- Mercaptopurine
- Inotuzumab Ozogamicin
Other Study ID Numbers
- A042001
- U10CA180821 (U.S. NIH Grant/Contract)
- NCI-2022-01735 (Registry Identifier: NCI Clinical Trial Reporting Program)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on B Acute Lymphoblastic Leukemia
-
Michael BurkeAmgenRecruitingRefractory B Acute Lymphoblastic Leukemia | B-cell Acute Lymphoblastic Leukemia | Relapsed B-cell Acute Lymphoblastic LeukemiaUnited States
-
Abramson Cancer Center of the University of PennsylvaniaWithdrawnB-cell Acute Lymphoblastic Leukemia | Refractory B-cell Acute Lymphoblastic Leukemia | Relapsed B-cell Acute Lymphoblastic Leukemia
-
Asan Medical CenterTerminatedLymphoblastic Lymphoma | Leukemia, Biphenotypic, Acute | Leukemia, Acute Lymphoblastic | Leukemia, Lymphoblastic, Acute, Philadelphia-Positive | Precursor B-Cell Lymphoblastic LeukemiaKorea, Republic of
-
Autolus LimitedCompletedCD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell Acute Lymphoblastic Leukemia (ALL) (AMELIA)Recurrent Childhood Acute Lymphoblastic Leukemia | B Acute Lymphoblastic Leukemia | B-cell Acute Lymphoblastic Leukemia | Refractory Childhood Acute Lymphoblastic LeukemiaUnited Kingdom
-
Novartis PharmaceuticalsCompletedB-cell Acute Lymphoblastic Leukemia | Refractory B-cell Acute Lymphoblastic Leukemia | Relapsed B-cell Acute Lymphoblastic LeukemiaUnited States
-
Medical College of WisconsinUniversity of Wisconsin, Madison; AmgenRecruitingB-cell Acute Lymphoblastic Leukemia | B-cell Childhood Acute Lymphoblastic Leukemia | B-Cell ALL, ChildhoodUnited States
-
Shenzhen BinDeBio Ltd.Xiangya Hospital of Central South UniversityRecruitingRelapsed B-cell Acute Lymphoblastic Leukemia, Childhood | Refractory B-cell Acute Lymphoblastic Leukemia, Childhood | Relapsed/Refractory B-cell Lymphoma, ChildhoodChina
-
Shenzhen BinDeBio Ltd.Children's Hospital of Fudan UniversityActive, not recruitingRelapsed B-cell Acute Lymphoblastic Leukemia, Childhood | Refractory B-cell Acute Lymphoblastic Leukemia, Childhood | Relapsed/Refractory B-cell Lymphoma, ChildhoodChina
-
Children's Oncology GroupRecruitingLymphoblastic Lymphoma | B Acute Lymphoblastic Leukemia | B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 | T Acute Lymphoblastic Leukemia | Mixed Phenotype Acute Leukemia | B Acute Lymphoblastic Leukemia, BCR-ABL1-LikeUnited States, Canada
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedAcute Lymphoblastic Leukemia | Adult B Acute Lymphoblastic Leukemia | Childhood B Acute Lymphoblastic LeukemiaUnited States
Clinical Trials on Cytarabine
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)RecruitingRecurrent Chronic Myelomonocytic Leukemia | Refractory Chronic Myelomonocytic Leukemia | Blasts More Than 5 Percent of Bone Marrow Nucleated Cells | Recurrent High Risk Myelodysplastic Syndrome | Refractory High Risk Myelodysplastic Syndrome | Blasts 10-19 Percent of Bone Marrow Nucleated Cells and other conditionsUnited States
-
Sunesis PharmaceuticalsCompletedAcute Myeloid LeukemiaUnited States, Canada, Spain, Belgium, Korea, Republic of, Australia, France, Germany, Poland, New Zealand, United Kingdom, Czechia, Austria, Hungary, Italy
-
Jianxiang WangUnknownAcute Myeloid LeukemiaChina
-
Ohio State University Comprehensive Cancer CenterNational Cancer Institute (NCI)RecruitingRefractory Acute Myeloid Leukemia | Blasts More Than 5 Percent of Bone Marrow Nucleated Cells | Persistent DiseaseUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedAcute Myeloid Leukemia | Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome | Secondary Acute Myeloid LeukemiaUnited States
-
Roswell Park Cancer InstituteJazz PharmaceuticalsRecruitingAcute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome | Secondary Acute Myeloid Leukemia | Therapy-Related Acute Myeloid Leukemia | Acute Myeloid Leukemia With Myelodysplasia-Related ChangesUnited States
-
M.D. Anderson Cancer CenterRecruitingMyelodysplastic Syndrome | Recurrent Acute Myeloid Leukemia | Refractory Acute Myeloid Leukemia | Myeloproliferative Neoplasm | Acute Myeloid Leukemia With Gene MutationsUnited States
-
M.D. Anderson Cancer CenterRecruitingRecurrent Acute Myeloid Leukemia | Refractory Acute Myeloid LeukemiaUnited States
-
Institute of Hematology & Blood Diseases Hospital...Recruiting
-
Fred Hutchinson Cancer CenterJazz PharmaceuticalsTerminatedAcute Myeloid Leukemia | Myelodysplastic Syndrome With Excess Blasts-2 | Myeloid NeoplasmUnited States