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

NCT ID: NCT00945815

Last Updated: 2017-11-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2017-08-31

Brief Summary

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.

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).

Conditions

Leukemia

Keywords

B-cell adult acute lymphoblastic leukemia; L1 adult acute lymphoblastic leukemia; L2 adult acute lymphoblastic leukemia; recurrent adult acute lymphoblastic leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

epratuzumab

Intervention Type: BIOLOGICAL

clofarabine

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

Interventions

epratuzumab

Intervention Type: BIOLOGICAL

clofarabine

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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)

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anjali Advani, MD

Role: STUDY_CHAIR

The Cleveland Clinic

Locations

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

USC/Norris Comprehensive Cancer Center and Hospital

Los Angeles, California, United States

University of California Davis Cancer Center

Sacramento, California, United States

Stanford Cancer Center

Stanford, California, United States

University of Colorado Cancer Center at UC Health Sciences Center

Aurora, Colorado, United States

St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center

Grand Junction, Colorado, United States

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Tampa, Florida, United States

Cardinal Bernardin Cancer Center at Loyola University Medical Center

Maywood, Illinois, United States

St. Francis Hospital and Health Centers - Beech Grove Campus

Beech Grove, Indiana, United States

Reid Hospital & Health Care Services

Richmond, Indiana, United States

Tulane Cancer Center Office of Clinical Research

Alexandria, Louisiana, United States

Hematology-Oncology Clinic

Baton Rouge, Louisiana, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

University of Mississippi Cancer Clinic

Jackson, Mississippi, United States

Saint Louis University Cancer Center

St Louis, Missouri, United States

CCOP - Montana Cancer Consortium

Billings, Montana, United States

St. Vincent Healthcare Cancer Care Services

Billings, Montana, United States

Hematology-Oncology Centers of the Northern Rockies - Billings

Billings, Montana, United States

Billings Clinic - Downtown

Billings, Montana, United States

Bozeman Deaconess Cancer Center

Bozeman, Montana, United States

Great Falls Clinic - Main Facility

Great Falls, Montana, United States

Sletten Cancer Institute at Benefis Healthcare

Great Falls, Montana, United States

St. Peter's Hospital

Helena, Montana, United States

Glacier Oncology, PLLC

Kalispell, Montana, United States

Kalispell Regional Medical Center

Kalispell, Montana, United States

Montana Cancer Specialists at Montana Cancer Center

Missoula, Montana, United States

Montana Cancer Center at St. Patrick Hospital and Health Sciences Center

Missoula, Montana, United States

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, United States

Presbyterian Cancer Center at Presbyterian Hospital

Charlotte, North Carolina, United States

Charles M. Barrett Cancer Center at University Hospital

Cincinnati, Ohio, United States

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Grandview Hospital

Dayton, Ohio, United States

Good Samaritan Hospital

Dayton, Ohio, United States

David L. Rike Cancer Center at Miami Valley Hospital

Dayton, Ohio, United States

Samaritan North Cancer Care Center

Dayton, Ohio, United States

CCOP - Dayton

Dayton, Ohio, United States

Blanchard Valley Medical Associates

Findlay, Ohio, United States

Middletown Regional Hospital

Franklin, Ohio, United States

Wayne Hospital

Greenville, Ohio, United States

Charles F. Kettering Memorial Hospital

Kettering, Ohio, United States

UVMC Cancer Care Center at Upper Valley Medical Center

Troy, Ohio, United States

Ruth G. McMillan Cancer Center at Greene Memorial Hospital

Xenia, Ohio, United States

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, United States

Cancer Centers of the Carolinas - Faris Road

Greenville, South Carolina, United States

Cancer Centers of the Carolinas - Grove Commons

Greenville, South Carolina, United States

CCOP - Greenville

Greenville, South Carolina, United States

Cancer Centers of the Carolinas - Greer Medical Oncology

Greer, South Carolina, United States

Cancer Centers of the Carolinas - Seneca

Seneca, South Carolina, United States

Cancer Centers of the Carolinas - Spartanburg

Spartanburg, South Carolina, United States

Baylor University Medical Center - Houston

Houston, Texas, United States

Ben Taub General Hospital

Houston, Texas, United States

St. Luke's Texas Cancer Institute at St. Luke's Episcopal Hospital

Houston, Texas, United States

Veterans Affairs Medical Center - Houston

Houston, Texas, United States

American Fork Hospital

American Fork, Utah, United States

Sandra L. Maxwell Cancer Center

Cedar City, Utah, United States

Logan Regional Hospital

Logan, Utah, United States

Jon and Karen Huntsman Cancer Center at Intermountain Medical Center

Murray, Utah, United States

Val and Ann Browning Cancer Center at McKay-Dee Hospital Center

Ogden, Utah, United States

Utah Valley Regional Medical Center - Provo

Provo, Utah, United States

LDS Hospital

Salt Lake City, Utah, United States

Dixie Regional Medical Center - East Campus

St. George, Utah, United States

Island Hospital Cancer Care Center at Island Hospital

Anacortes, Washington, United States

St. Joseph Cancer Center

Bellingham, Washington, United States

Olympic Hematology and Oncology

Bremerton, Washington, United States

Highline Medical Center Cancer Center

Burien, Washington, United States

Swedish Medical Center - Issaquah Campus

Issaquah, Washington, United States

Columbia Basin Hematology

Kennewick, Washington, United States

Skagit Valley Hospital Cancer Care Center

Mount Vernon, Washington, United States

Harrison Poulsbo Hematology and Onocology

Poulsbo, Washington, United States

Harborview Medical Center

Seattle, Washington, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Group Health Central Hospital

Seattle, Washington, United States

Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

Seattle, Washington, United States

Polyclinic First Hill

Seattle, Washington, United States

University Cancer Center at University of Washington Medical Center

Seattle, Washington, United States

North Puget Oncology at United General Hospital

Sedro-Woolley, Washington, United States

Cancer Care Northwest - Spokane South

Spokane, Washington, United States

Evergreen Hematology and Oncology, PS

Spokane, Washington, United States

Wenatchee Valley Medical Center

Wenatchee, Washington, United States

Welch Cancer Center at Sheridan Memorial Hospital

Sheridan, Wyoming, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29618479 (View on PubMed)

Other Identifiers

S0910

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA032102

Identifier Type: NIH

Identifier Source: secondary_id

View Link

S0910

Identifier Type: -

Identifier Source: org_study_id