S0910 Epratuzumab, Cytarabine, and Clofarabine in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia

S0910, A Phase II Study of Epratuzumab (NSC-716711) in Combination With Cytarabine and Clofarabine for Patients With Relapsed or Refractory Ph- Negative Precursor B-Cell Acute Lymphoblastic Leukemia

RATIONALE: Monoclonal antibodies, such as epratuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cytarabine and clofarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving epratuzumab together with cytarabine and clofarabine may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects and how well giving epratuzumab together with cytarabine and clofarabine works in treating patients with relapsed or refractory acute lymphoblastic leukemia.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Other: laboratory biomarker analysis; Drug: cytarabine; Drug: clofarabine; Biological: epratuzumab

Detailed Description

OBJECTIVES:

• To test whether the complete remission (CR) rate (CR and incomplete CR) in adult patients with relapsed or refractory precursor B-cell acute lymphoblastic leukemia is sufficiently high after treatment with cytarabine, clofarabine, and epratuzumab to warrant further investigation.
• To estimate the frequency and severity of toxicities associated with the dosing schedule of cytarabine, clofarabine, and epratuzumab used in this study.
• To investigate, preliminarily, the effect of laboratory correlates (minimal post-treatment residual disease) and cytogenetic factors on prognosis in this patient population. (Not reported here due to limited MRD data)

OUTLINE: This is a multicenter study.

Patients receive cytarabine IV over 2 hours on days 1-5, clofarabine IV over 1 hour on days 2-6, and epratuzumab IV over at least 1 hour on days 7, 14, 21, and 28 in the absence of disease progression or unacceptable toxicity*.

NOTE: * Prophylactic intrathecal methotrexate is required for patients < 22 years of age, and is recommended (but not required) for patients ≥ 22 years of age.

Blood samples, bone marrow samples, and/or tumor tissue samples may be collected for further laboratory analysis.

Patients are followed up every 3 months for 2 years, then annually for 3 years (until 5 years after registration).

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90089-9181
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • Stanford, California, United States, 94305-5824
      • Stanford Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center at UC Health Sciences Center
    • Grand Junction, Colorado, United States, 81502
      • St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
  • Florida
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers - Beech Grove Campus
    • Richmond, Indiana, United States, 47374
      • Reid Hospital & Health Care Services
  • Louisiana
    • Alexandria, Louisiana, United States, 71315-3198
      • Tulane Cancer Center Office of Clinical Research
    • Baton Rouge, Louisiana, United States, 70809
      • Hematology-Oncology Clinic
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0942
      • University of Michigan Comprehensive Cancer Center
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Cancer Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Cancer Center
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare Cancer Care Services
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
    • Billings, Montana, United States, 59102
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic - Main Facility
    • Great Falls, Montana, United States, 59405
      • Sletten Cancer Institute at Benefis Healthcare
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Missoula, Montana, United States, 59807-7877
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • New York
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28233-3549
      • Presbyterian Cancer Center at Presbyterian Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Charles M. Barrett Cancer Center at University Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Cancer Care Center
    • Dayton, Ohio, United States, 45420
      • CCOP - Dayton
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Medical Associates
    • Franklin, Ohio, United States, 45005-1066
      • Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Troy, Ohio, United States, 45373-1300
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center at Medical University of South Carolina
    • Greenville, South Carolina, United States, 29615
      • CCOP - Greenville
    • Greenville, South Carolina, United States, 29605
      • Cancer Centers of the Carolinas - Faris Road
    • Greenville, South Carolina, United States, 29605
      • Cancer Centers of the Carolinas - Grove Commons
    • Greer, South Carolina, United States, 29650
      • Cancer Centers of the Carolinas - Greer Medical Oncology
    • Seneca, South Carolina, United States, 29672
      • Cancer Centers of the Carolinas - Seneca
    • Spartanburg, South Carolina, United States, 29307
      • Cancer Centers of the Carolinas - Spartanburg
  • Texas
    • Houston, Texas, United States, 77030
      • Ben Taub General Hospital
    • Houston, Texas, United States, 77030
      • Veterans Affairs Medical Center - Houston
    • Houston, Texas, United States, 77030
      • Baylor University Medical Center - Houston
    • Houston, Texas, United States, 77030
      • St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital
  • Utah
    • American Fork, Utah, United States, 84003
      • American Fork Hospital
    • Cedar City, Utah, United States, 84720
      • Sandra L. Maxwell Cancer Center
    • Logan, Utah, United States, 84321
      • Logan Regional Hospital
    • Murray, Utah, United States, 84157
      • Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
    • Ogden, Utah, United States, 84403
      • Val and Ann Browning Cancer Center at McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
  • Washington
    • Anacortes, Washington, United States, 98221
      • Island Hospital Cancer Care Center at Island Hospital
    • Bellingham, Washington, United States, 98225
      • St. Joseph Cancer Center
    • Bremerton, Washington, United States, 98310
      • Olympic Hematology and Oncology
    • Burien, Washington, United States, 98166
      • Highline Medical Center Cancer Center
    • Issaquah, Washington, United States, 98029
      • Swedish Medical Center - Issaquah Campus
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital Cancer Care Center
    • Poulsbo, Washington, United States, 98370
      • Harrison Poulsbo Hematology and Onocology
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98112
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98122-4307
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Seattle, Washington, United States, 98122
      • Polyclinic First Hill
    • Seattle, Washington, United States, 98195
      • University Cancer Center at University of Washington Medical Center
    • Sedro-Woolley, Washington, United States, 98284
      • North Puget Oncology at United General Hospital
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology, PS
    • Wenatchee, Washington, United States, 98801-2028
      • Wenatchee Valley Medical Center
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center at Sheridan Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 120 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Morphologically confirmed precursor B-cell acute lymphoblastic leukemia (ALL) (non T-cell)

  • Must have evidence of disease in bone marrow or peripheral blood

    • Immunophenotyping of the blood or marrow lymphoblasts must be performed to determine lineage (B cell, T cell, or mixed B/T cell)
    • Must have ≥ 5% lymphoblasts present in the blood or bone marrow

    • At least 20% of marrow and/or peripheral blood lymphoblasts must be CD22+ by flow cytometry

      • Co-expression of myeloid antigens (CD13 and CD33) allowed
    • Patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible

• Philadelphia (Ph) chromosome-negative disease

  • Patients with unknown Ph status by cytogenetics or FISH and unknown BCR/ABL status by PCR are eligible for study registration, but must be removed from study therapy if found to be Ph+ or BCR/ABL+ after study registration

• Refractory to a standard induction regimen that included vincristine and prednisone or high-dose cytarabine or mitoxantrone OR relapsed after successful prior induction therapy

  • Any number of prior induction therapies or any number of remissions achieved are allowed
• No M0 acute myeloid leukemia, mixed lineage leukemia, or L3 (Burkitt) leukemia

• No active CNS involvement by clinical evaluation

  • Patients with a documented history of CNS involvement of ALL or with clinical signs or symptoms consistent with CNS involvement of ALL must undergo a lumbar puncture that is negative for CNS involvement of ALL
• Patients < 22 years of age must be willing to receive prophylactic intrathecal chemotherapy
• Must be registered on SWOG-9007 "Cytogenetic Studies in Leukemia Patients" (closed as of 07/01/2010)

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2
• Serum creatinine ≤ 1.0 mg/dL OR glomerular filtration rate > 60 mL/min
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 2.5 times ULN
• Bilirubin ≤ 1.5 times ULN
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment

• HIV-positive patients are eligible (at the discretion of the investigator) provided the following criteria are met:

  • No history of AIDS-defining conditions
  • CD4 cell count > 350/mm³
  • If on antiretroviral agents, must not include zidovudine or stavudine
  • Willing to receive prophylaxis for pneumocystis jirovecii pneumonia during study therapy (regardless of CD4 cell count) until the CD4 cell count is > 200/mm³ after completion of study treatment
• Prior malignancy (other than ALL) allowed provided it is in remission and there are no plans to treat the malignancy at the time of study registration
• No uncontrolled systemic fungal, bacterial, viral, or other infection, defined as exhibiting ongoing signs or symptoms related to the infection with no improvement despite appropriate antibiotics or other treatment
• No neuropathy (cranial, motor or sensory) ≥ grade 2

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Any number of prior therapies allowed

• More than 90 days since prior allogeneic bone marrow transplant (BMT)

  • No concurrent immunosuppression therapy for the treatment of graft-vs-host disease (GVHD)
  • No acute GVHD ≥ grade 2, moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity

• Prior autologous BMT allowed

  • No concurrent immunosuppression therapy for the treatment of GVHD

• More than 14 days since prior chemotherapy, investigational agents, or major surgery and recovered

  • Maintenance therapy with steroids, vincristine, and/or anti-metabolite agents, including but not limited to, mercaptopurine, thioguanine, and methotrexate allowed
  • Concurrent hydroxyurea to reduce WBC to a reasonable level (as deemed by the treating physician) allowed
• No prior clofarabine or epratuzumab
• No other concurrent cytotoxic therapy or investigational therapy
• No concurrent alternative medications (e.g., herbal or botanical medications for anticancer purposes)
• Concurrent participation on SWOG-S9910 "Leukemia Centralized Reference Laboratories and Tissue Repositories, Ancillary" allowed (closed as of 07/01/2010)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: treatment; AraC 1 g/m2/d IV Days 1-5 clofarabine 40 mg/m2/d IV Days 2-6 epratuzumab 360 mg/m2/d IV Days 7, 14, 21, 28 acetaminophen 650 mg/d PO Days 7, 14, 21, 28 diphenhydramine 50 mg/d IV Days 7, 14, 21, 28 IT methotrexate 12 mg IT at least 1 wk apart during induction All give 1 cycle	Other: laboratory biomarker analysis; Drug: cytarabine; Drug: clofarabine; Biological: epratuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Remission	Complete remission (CR) is defined as: <5% marrow aspirate blasts. Blasts can be >=5% if the blasts are found to be myeloid and there is no evidence of lymphoblasts by flow cytometry or immunostaining. Neutrophils >= 1000/mcl; platelets >100,000/mcl; and no blasts in the peripheral blood. C1 Extramedullary disease status as defined in the protocol. Complete remission with incomplete platelet recovery (CRi) is same as CR but platelet count may be <=100,000/mcl and/or ANC may be <1,000/mcl.	After induction therapy was completed (1 or 2 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Grade 3 Through 5 Treatment-Related Adverse Events	Only adverse events that are possibly, probably or definitely related to study drug are reported. Any CTCAE 4.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.	Up to 5 years

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Statler A, Othus M, Erba HP, Chauncey TR, Radich JP, Coutre S, Advani A, Nand S, Ravandi F, Mukherjee S, Sekeres MA. Comparable outcomes of patients eligible vs ineligible for SWOG leukemia studies. Blood. 2018 Jun 21;131(25):2782-2788. doi: 10.1182/blood-2018-01-826693. Epub 2018 Apr 4.

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (ACTUAL): March 1, 2013
• Study Completion (ACTUAL): August 1, 2017

Study Registration Dates

• First Submitted: July 23, 2009
• First Submitted That Met QC Criteria: July 23, 2009
• First Posted (ESTIMATE): July 24, 2009

Study Record Updates

• Last Update Posted (ACTUAL): November 6, 2017
• Last Update Submitted That Met QC Criteria: October 3, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: B-cell adult acute lymphoblastic leukemia; recurrent adult acute lymphoblastic leukemia; L1 adult acute lymphoblastic leukemia; L2 adult acute lymphoblastic leukemia
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Epratuzumab; Clofarabine; Cytarabine
• Other Study ID Numbers: S0910 (OTHER: SWOG); U10CA032102 (U.S. NIH Grant/Contract)