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

Phase III, Randomized, Multicenter Study to Assess the Efficacy and Safety of HuM195 (Recombinant Humanized Anti-CD33 Monoclonal Antibody) in Combination With Standardized Chemotherapy Compared to Standardized Chemotherapy Alone in the Treatment of Patients With Refractory or First-Relapsed Acute Myelogenous Leukemia (AML)

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.

Study Overview

• Status: Unknown
• Conditions: Leukemia
• Intervention / Treatment: Drug: mitoxantrone hydrochloride; Drug: cytarabine; Drug: etoposide; Biological: lintuzumab

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2020
    • Algemeen Ziekenhuis Middelheim
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Leuven, Belgium, B-3000
    • U.Z. Gasthuisberg
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Queen Elizabeth II Health Science Center
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
• France
  • Angers, France, 49033
    • Centre Hospitalier Regional et Universitaire d'Angers
  • Vandoeuvre-Les-Nancy, France, 54511
    • CHRU de Nancy - Hopitaux de Brabois
• Germany
  • Berlin, Germany, D-12200
    • Universitaetsklinikum Benjamin Franklin
  • Frankfurt, Germany, D-60590
    • Klinikum der J.W. Goethe Universitaet
  • Munich, Germany, D-81675
    • Klinikum Rechts Der Isar/Technische Universitaet Muenchen
  • Munster, Germany, DOH-4-8149
    • Westfaelische Wilhelms-Universitaet
  • Rostock, Germany, 18057
    • University of Rostock
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum
• United Kingdom
  • England
    • Cambridge, England, United Kingdom, CB2 2QQ
      • Addenbrooke's NHS Trust
    • Hampstead, London, England, United Kingdom, NW3 2QG
      • Royal Free Hospital
    • Leeds, England, United Kingdom, LS1 3EX
      • Leeds Teaching Hospital Trust
    • Manchester, England, United Kingdom, M20 4BX
      • Christie Hospital N.H.S. Trust
• United States
  • California
    • Los Angeles, California, United States, 90033-0800
      • USC/Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center, UCLA
    • Los Angeles, California, United States, 91010
      • Beckman Research Institute, City of Hope
    • Orange, California, United States, 92613-5600
      • St. Joseph Hospital - Orange
    • Sacramento, California, United States, 95816
      • Sutter Cancer Center
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
    • San Diego, California, United States, 92121
      • Sidney Kimmel Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Cancer Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Clinic
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Louisiana
    • Shreveport, Louisiana, United States, 71130-3932
      • Louisiana State University School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Oncology Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital Cancer Center
    • Boston, Massachusetts, United States, 02111
      • New England Medical Center Hospital
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Hematology and Oncology Associates, Ltd.
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University Barnard Cancer Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Nevada Cancer Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Cancer Institute of New Jersey
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein Comprehensive Cancer Center
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital - Cornell Campus
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center, UNC
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
  • Ohio
    • Akron, Ohio, United States, 44302
      • Akron General Medical Center
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Tennessee
    • Memphis, Tennessee, United States, 38117
      • West Clinic, P.C.
    • Nashville, Tennessee, United States, 37232-2516
      • Vanderbilt University Medical Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT

Collaborators and Investigators

• Sponsor: Facet Biotech
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Daniel Levitt, MD, PhD, Facet Biotech

Study record dates

Study Major Dates

• Study Start: March 1, 2000

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: April 12, 2004
• First Posted (Estimate): April 13, 2004

Study Record Updates

• Last Update Posted (Estimate): November 6, 2013
• Last Update Submitted That Met QC Criteria: November 5, 2013
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: secondary acute myeloid leukemia; recurrent adult acute myeloid leukemia; adult acute erythroid leukemia (M6); adult acute megakaryoblastic leukemia (M7); adult acute minimally differentiated myeloid leukemia (M0); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); adult acute myelomonocytic leukemia (M4)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Etoposide; Cytarabine; Mitoxantrone; Lintuzumab
• Other Study ID Numbers: CDR0000068061; PDL-195-301; MSKCC-00029; UCLA-9910050; NCI-G00-1819