Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With Refractory or Relapsed Acute Myelogenous Leukemia

NCT ID: NCT00006045

Last Updated: 2013-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2000-03-31

Brief Summary

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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known if chemotherapy is more effective with or without monoclonal antibody therapy for acute myelogenous leukemia.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without monoclonal antibody therapy in treating patients who have refractory or relapsed acute myelogenous leukemia.

Detailed Description

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OBJECTIVES: I. Compare the efficacy, safety, pharmacokinetics, and immunogenicity of mitoxantrone, etoposide, and cytarabine (MEC) with or without monoclonal antibody HuG1-M195 in patients with refractory or relapsed acute myelogenous leukemia.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by age (under 50 vs 50 and over) and duration of previous complete remission (CR) (0-6 vs 7-12 months). All patients receive induction chemotherapy comprised of cytarabine IV over 2 hours, mitoxantrone IV over a maximum of 20 minutes, and etoposide IV over 1-2 hours on days 1-6. On day 5 of induction, patients are randomized to one of two treatment arms: Arm I: Patients receive day 6 of induction chemotherapy. Patients then receive monoclonal antibody HuG1-M195 (MOAB HuM195) IV over 4 hours on days 6-9 or 7-10. Treatment with MOAB HuM195 repeats every 2 weeks for 2 courses (courses 1 and 2) in the absence of disease progression or unacceptable toxicity. During course 1, MOAB HuM195 begins 30 minutes to 24 hours postchemotherapy. Patients who do not achieve CR by day 70 of induction and show evidence of bone marrow progression (regimen failure (RF)) are taken off study. Patients without RF are assigned to one of two consolidation groups based on response: Group A (CR): Patients receive consolidation chemotherapy comprised of mitoxantrone IV over a maximum of 20 minutes on days 1 and 2, and cytarabine IV over 2 hours and etoposide IV over 1-2 hours on days 1-4. Patients with New York Heart Association class II heart disease preconsolidation receive no mitoxantrone during consolidation. Patients receive MOAB HuM195 IV over 4 hours on days 4-7 or 5-8. Treatment with MOAB HuM195 repeats every 2 weeks for 2 additional courses (courses 3 and 4). During course 3, MOAB HuM195 begins 30 minutes to 24 hours postchemotherapy. Group B (partial remission (PR), hematologic improvement (HI), or stable disease (SD)): Patients receive MOAB HuM195 as in group A but no consolidation chemotherapy. Patients without RF after treatment on group A or B receive maintenance MOAB HuM195 IV over 4 hours on days 1-4. Treatment repeats every month for 8 additional courses (courses 5-12). Arm II: Patients receive day 6 of induction chemotherapy. Patients receive no MOAB HuM195 during the entire study. Patients without RF at day 70 of induction are assigned to one of two consolidation groups based on response: Group C (CR): Patients receive consolidation chemotherapy as in group A. Group D (PR, HI, or SD): Patients receive no further treatment. Patients may be eligible to receive MOAB HuM195 on PDL Study 195-302. Patients are followed every 3 months for 1 year, and then every 6 months thereafter.

PROJECTED ACCRUAL: A maximum of 200 patients (100 per arm) will be accrued for this study.

Conditions

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Leukemia

Keywords

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recurrent adult acute myeloid leukemia adult acute erythroid leukemia (M6) adult acute myeloblastic leukemia without maturation (M1) adult acute myeloblastic leukemia with maturation (M2) adult acute myelomonocytic leukemia (M4) adult acute monoblastic leukemia (M5a) adult acute megakaryoblastic leukemia (M7) secondary acute myeloid leukemia adult acute monocytic leukemia (M5b) adult acute minimally differentiated myeloid leukemia (M0)

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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lintuzumab

Intervention Type BIOLOGICAL

cytarabine

Intervention Type DRUG

etoposide

Intervention Type DRUG

mitoxantrone hydrochloride

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically proven acute myelogenous leukemia (AML) that may have been primary AML, secondary AML, or preceded by hematologic disorder All FAB subtypes except M3 Must meet one of the following three criteria: First relapse within 1 year after documentation of a previous complete remission (CR) achieved by chemotherapy Refractory to prior chemotherapy comprised of a minimum of 1 induction course, including cytarabine at a minimum of 500 mg/m2 (e.g., 100 mg/m2/day for 5 days) plus an anthracycline No high dose cytarabine (no cumulative dose greater than 3 g/m2) First relapse from a previous CR with subsequent autologous bone marrow transplantation (BMT), only if all of the following criteria are met: First BMT At least 100 days but less than 1 year posttransplantation At least 25% cellularity of the bone marrow Previous BMT included full hematopoietic recovery, defined by all of the following: Hemoglobin at least 10 g/dL (without transfusion) Platelet count at least 100,000/mm3 (without transfusion) Absolute neutrophil count at least 1,500/mm3 No transplantation candidates Bone marrow blasts (leukemic cells) greater than 10% No chronic myelogenous leukemia in blast crisis No active CNS leukemia

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 50-100% Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin less than 2.0 mg/dL (unless related to Gilbert's disease or due to leukemic infiltration) SGOT or SGPT no greater than 4 times upper limit of normal (unless related to AML) Renal: Creatinine less than 2.0 mg/dL (unless related to AML) Cardiovascular: Left ventricular function normal No unstable cardiac arrhythmias, unstable angina pectoris, or myocardial infarction within the past 6 months No New York Heart Association class III or IV heart disease No electrocardiogram evidence of active ischemia Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 1 month after study HIV negative No other active malignancy requiring therapy No active serious infection that is uncontrolled by antimicrobial therapy Medically stable No significant organ dysfunction

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics At least 30 days since prior experimental biologic therapy (e.g., interleukin-2) No concurrent biologic therapy, including bone marrow transplantation Chemotherapy: See Disease Characteristics For first relapse AML with recent or prior chemotherapy: Prior hydroxyurea given as a short course (up to 48 hours) allowed, if needed, to reduce the peripheral leukocyte count Hydroxyurea must be discontinued prior to study For refractory AML with recent or prior chemotherapy: Greater than 2 weeks since prior chemotherapy except hydroxyurea given as above No other concurrent chemotherapy Endocrine therapy: Not specified Radiotherapy: No concurrent radiotherapy Surgery: Not specified Other: No other concurrent experimental therapy Concurrent therapy for other preexisting diseases allowed
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Facet Biotech

INDUSTRY

Sponsor Role lead

Principal Investigators

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Daniel Levitt, MD, PhD

Role: STUDY_CHAIR

Facet Biotech

Locations

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USC/Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status

Jonsson Comprehensive Cancer Center, UCLA

Los Angeles, California, United States

Site Status

Beckman Research Institute, City of Hope

Los Angeles, California, United States

Site Status

St. Joseph Hospital - Orange

Orange, California, United States

Site Status

Sutter Cancer Center

Sacramento, California, United States

Site Status

University of California Davis Cancer Center

Sacramento, California, United States

Site Status

Sidney Kimmel Cancer Center

San Diego, California, United States

Site Status

Washington Cancer Institute

Washington D.C., District of Columbia, United States

Site Status

Emory Clinic

Atlanta, Georgia, United States

Site Status

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Louisiana State University School of Medicine

Shreveport, Louisiana, United States

Site Status

Johns Hopkins Oncology Center

Baltimore, Maryland, United States

Site Status

New England Medical Center Hospital

Boston, Massachusetts, United States

Site Status

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Site Status

North Mississippi Hematology and Oncology Associates, Ltd.

Tupelo, Mississippi, United States

Site Status

Washington University Barnard Cancer Center

St Louis, Missouri, United States

Site Status

Nevada Cancer Center

Las Vegas, Nevada, United States

Site Status

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

New York Presbyterian Hospital - Cornell Campus

New York, New York, United States

Site Status

Albert Einstein Comprehensive Cancer Center

The Bronx, New York, United States

Site Status

New York Medical College

Valhalla, New York, United States

Site Status

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

Akron General Medical Center

Akron, Ohio, United States

Site Status

Ireland Cancer Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Site Status

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status

West Clinic, P.C.

Memphis, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Algemeen Ziekenhuis Middelheim

Antwerp, , Belgium

Site Status

Institut Jules Bordet

Brussels, , Belgium

Site Status

U.Z. Gasthuisberg

Leuven, , Belgium

Site Status

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status

Health Sciences Centre

Winnipeg, Manitoba, Canada

Site Status

Queen Elizabeth II Health Science Center

Halifax, Nova Scotia, Canada

Site Status

Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status

Centre Hospitalier Regional et Universitaire d'Angers

Angers, , France

Site Status

CHRU de Nancy - Hopitaux de Brabois

Vandœuvre-lès-Nancy, , France

Site Status

Universitaetsklinikum Benjamin Franklin

Berlin, , Germany

Site Status

Klinikum der J.W. Goethe Universitaet

Frankfurt, , Germany

Site Status

Klinikum Rechts Der Isar/Technische Universitaet Muenchen

Munich, , Germany

Site Status

Westfaelische Wilhelms-Universitaet

Münster, , Germany

Site Status

University of Rostock

Rostock, , Germany

Site Status

Academisch Medisch Centrum

Amsterdam, , Netherlands

Site Status

Addenbrooke's NHS Trust

Cambridge, England, United Kingdom

Site Status

Royal Free Hospital

Hampstead, London, England, United Kingdom

Site Status

Leeds Teaching Hospital Trust

Leeds, England, United Kingdom

Site Status

Christie Hospital N.H.S. Trust

Manchester, England, United Kingdom

Site Status

Countries

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United States Belgium Canada France Germany Netherlands United Kingdom

Other Identifiers

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PDL-195-301

Identifier Type: -

Identifier Source: secondary_id

MSKCC-00029

Identifier Type: -

Identifier Source: secondary_id

UCLA-9910050

Identifier Type: -

Identifier Source: secondary_id

NCI-G00-1819

Identifier Type: -

Identifier Source: secondary_id

CDR0000068061

Identifier Type: -

Identifier Source: org_study_id