Comparison of Three Treatment Regimens in Treating Patients With Relapsed or Refractory Acute Myelogenous Leukemia

NCT ID: NCT00005962

Last Updated: 2023-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-10-04
• Study Completion Date: 2007-06-30

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as gemtuzumab ozogamicin can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining more than one drug or combining monoclonal antibody with chemotherapy may kill more cancer cells. It is not yet known which treatment regimen is more effective for acute myelogenous leukemia.

PURPOSE: Randomized phase II trial to compare the effectiveness of three treatment regimens in treating patients who have relapsed or refractory acute myelogenous leukemia.

Detailed Description

OBJECTIVES:

• Compare the rates of complete response (CR) and CR without full platelet recovery in patients with relapsed or refractory acute myelogenous leukemia treated with gemtuzumab ozogamicin and cytarabine vs daunorubicin liposomal and cytarabine vs cyclophosphamide, cytarabine, and topotecan.
• Compare the toxicities of these 3 regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by disease status (relapse less than 6 months after first complete response (CR) vs relapse 6-12 months after first CR vs refractory to conventional initial induction chemotherapy (no more than 2 courses) or first reinduction (no more than 1 course) vs second or greater relapse).

• Induction: Patients are randomized to 1 of 3 treatment arms:

• Arm I: Patients receive cytarabine IV over 2 hours on days 1-4 and gemtuzumab ozogamicin IV over 2 hours on day 5.
• Arm II: Patients receive daunorubicin liposomal IV over a minimum of 2 hours on days 1-3 and cytarabine IV over 2 hours (beginning immediately after completion of daunorubicin liposomal infusion) on days 1-4.
• Arm III: Patients receive cyclophosphamide IV over 1 hour every 12 hours on days 1-3, cytarabine IV over 2 hours (beginning immediately after completion of cyclophosphamide infusion) on days 2-6, and topotecan IV continuously on days 2-6.
• Consolidation: Patients who achieve complete remission (CR) receive 1 additional course of induction therapy on the same arm to which they were originally randomized beginning within 4-6 weeks after initial documentation of CR. Patients on arm II receive no additional daunorubicin liposomal if resting ejection fraction is less than 50% preconsolidation. All patients receive sargramostim (GM-CSF) IV over 4 hours or SQ daily beginning 24 hours after completion of consolidation therapy and continuing until blood counts recover.

Patients are followed every 3 months through year 2, every 6 months through year 5, and then annually thereafter until death.

PROJECTED ACCRUAL: A maximum of 150-165 patients (50-55 per arm) will be accrued for this study within 2 years.

Conditions

Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

sargramostim

Intervention Type: BIOLOGICAL

cyclophosphamide

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

gemtuzumab ozogamicin

Intervention Type: DRUG

liposomal daunorubicin citrate

Intervention Type: DRUG

topotecan hydrochloride

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Acute myelomonocytic leukemia (FAB type M4)
• Acute monocytic leukemia (FAB type M5)
• Acute erythroleukemia (FAB type M6)
• Acute megakaryocytic leukemia (FAB type M7)
• Must meet 1 of the following criteria:

• Relapse less than 6 months after first complete remission (CR)
• Relapse 6-12 months after first CR
• Refractory to conventional initial induction chemotherapy (no more than 2 courses) or first reinduction (no more than 1 course)

• Must have marrow documentation of residual leukemia after chemotherapy (for at least 2 weeks duration)
• Second or greater relapse
• No relapse greater than 1 year after achieving first CR
• Blast cells must be CD33 positive
• Prior CNS leukemia allowed if there is currently documentation of no CNS involvement on CSF examination (i.e., negative CSF by lumbar puncture)

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 2.0 mg/dL*
• SGOT less than 2 times upper limit of normal* NOTE: *Unless due to leukemia infiltration

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• See Chemotherapy
• No myocardial infarction within the past 3 months
• No significant congestive heart failure
• No significant cardiac arrhythmia
• Cardiac ejection fraction normal by MUGA scan or echocardiogram
• Resting ejection fraction at least 50% or at least 5% increase with exercise
• Shortening fraction at least 24% or normal by echocardiogram

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No concurrent organ damage or other medical problems that would precludestudy therapy
• No concurrent evidence (including positive blood or deep tissue cultures or stains) of invasive fungal infection
• No hypersensitivity to ingredients of gemtuzumab ozogamicin or daunorubicin liposomal
• No other active tumor that would interfere with study therapy or increase risk

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior gemtuzumab ozogamicin

Chemotherapy:

• See Disease Characteristics
• See Biologic therapy
• No prior daunorubicin liposomal or topotecan
• Prior doxorubicin (no greater than 300 mg/m2), daunorubicin (no greater than 300 mg/m2), idarubicin (no greater than 100 mg/m2), or mitoxantrone (no greater than 100 mg/m2) allowed if left ventricular function is adequate
• At least 4 weeks since prior chemotherapy except patients who are refractory to conventional initial induction chemotherapy
• Prior hydroxyurea allowed within 4 weeks prior to beginning study
• Hydroxyurea must be discontinued at least 24 hours prior to beginning study

Endocrine therapy:

• Not specified

Radiotherapy:

• At least 4 weeks since prior radiotherapy except patients who are refractory to conventional initial induction chemotherapy

Surgery:

• Not specified

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role: lead

Principal Investigators

Mark R. Litzow, MD

Role: STUDY_CHAIR

Mayo Clinic

Locations

CCOP - Scottsdale Oncology Program

Scottsdale, Arizona, United States

Cancer Center and Beckman Research Institute, City of Hope

Duarte, California, United States

Veterans Affairs Medical Center - Palo Alto

Palo Alto, California, United States

Stanford University Medical Center

Stanford, California, United States

CCOP - Colorado Cancer Research Program, Inc.

Denver, Colorado, United States

CCOP - Christiana Care Health Services

Wilmington, Delaware, United States

Veterans Affairs Medical Center - Gainsville

Gainesville, Florida, United States

Veterans Affairs Medical Center - Miami

Miami, Florida, United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Veterans Affairs Medical Center - Tampa (Haley)

Tampa, Florida, United States

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, United States

Veterans Affairs Medical Center - Lakeside Chicago

Chicago, Illinois, United States

CCOP - Central Illinois

Decatur, Illinois, United States

CCOP - Evanston

Evanston, Illinois, United States

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

CCOP - Carle Cancer Center

Urbana, Illinois, United States

Indiana University Cancer Center

Indianapolis, Indiana, United States

Veterans Affairs Medical Center - Indianapolis (Roudebush)

Indianapolis, Indiana, United States

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, United States

CCOP - Iowa Oncology Research Association

Des Moines, Iowa, United States

Holden Comprehensive Cancer Center at The University of Iowa

Iowa City, Iowa, United States

MBCCOP - LSU Health Sciences Center

New Orleans, Louisiana, United States

CCOP - Ochsner

New Orleans, Louisiana, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

New England Medical Center Hospital

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

CCOP - Ann Arbor Regional

Ann Arbor, Michigan, United States

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

CCOP - Duluth

Duluth, Minnesota, United States

Veterans Affairs Medical Center - Minneapolis

Minneapolis, Minnesota, United States

University of Minnesota Cancer Center

Minneapolis, Minnesota, United States

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

Veterans Affairs Medical Center - Omaha

Omaha, Nebraska, United States

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Veterans Affairs Medical Center - East Orange

East Orange, New Jersey, United States

CCOP - Northern New Jersey

Hackensack, New Jersey, United States

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Veterans Affairs Medical Center - Brooklyn

Brooklyn, New York, United States

Veterans Affairs Medical Center - New York

New York, New York, United States

NYU School of Medicine's Kaplan Comprehensive Cancer Center

New York, New York, United States

University of Rochester Cancer Center

Rochester, New York, United States

Albert Einstein Comprehensive Cancer Center

The Bronx, New York, United States

MBCCOP-Our Lady of Mercy Cancer Center

The Bronx, New York, United States

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

Ireland Cancer Center

Cleveland, Ohio, United States

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

CCOP - Columbus

Columbus, Ohio, United States

CCOP - Toledo Community Hospital Oncology Program

Toledo, Ohio, United States

CCOP - Oklahoma

Tulsa, Oklahoma, United States

Hahnemann University Hospital

Philadelphia, Pennsylvania, United States

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

Kimmel Cancer Center of Thomas Jefferson University - Philadelphia

Philadelphia, Pennsylvania, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Veterans Affairs Medical Center - Pittsburgh

Pittsburgh, Pennsylvania, United States

CCOP - MainLine Health

Wynnewood, Pennsylvania, United States

CCOP - Sioux Community Cancer Consortium

Sioux Falls, South Dakota, United States

Veterans Affairs Medical Center - Madison

Madison, Wisconsin, United States

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

CCOP - Marshfield Medical Research and Education Foundation

Marshfield, Wisconsin, United States

MBCCOP - San Juan

San Juan, , Puerto Rico

Veterans Affairs Medical Center - San Juan

San Juan, , Puerto Rico

Pretoria Academic Hospitals

Pretoria, , South Africa

Countries

United States; Puerto Rico; South Africa

References

Litzow MR, Othus M, Cripe LD, Gore SD, Lazarus HM, Lee SJ, Bennett JM, Paietta EM, Dewald GW, Rowe JM, Tallman MS; Eastern Cooperative Oncology Group Leukemia Committee. Failure of three novel regimens to improve outcome for patients with relapsed or refractory acute myeloid leukaemia: a report from the Eastern Cooperative Oncology Group. Br J Haematol. 2010 Jan;148(2):217-25. doi: 10.1111/j.1365-2141.2009.07917.x. Epub 2009 Oct 5.

Reference Type: RESULT

PMID: 19804455 (View on PubMed)

Litzow MR, Goloubeva O, Rowe J, et al.: A randomized phase II trial of gemtuzumab ozogamicin vs. liposomal daunorubicin vs. cyclophosphamide plus topotecan, each combined with intermediate dose Ara-C for the treatment of patients with relapsed or refractory acute myelogenous leukemia . [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-2359, 2003.

Reference Type: RESULT

Other Identifiers

E-4999

Identifier Type: -

Identifier Source: secondary_id

CDR0000067944

Identifier Type: -

Identifier Source: org_study_id