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Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With Refractory or Relapsed Acute Myelogenous Leukemia
This study is ongoing, but not recruiting participants.
First Received: July 5, 2000   Last Updated: February 6, 2009   History of Changes
Sponsor: PDL BioPharma, Inc.
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00006045
  Purpose

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.


Condition Intervention Phase
Leukemia
Biological: lintuzumab
Drug: cytarabine
Drug: etoposide
Drug: mitoxantrone hydrochloride
Phase III

Study Type: Interventional
Study Design: Treatment
Official Title: 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 Standarized Chemotherapy Alone in the Treatment of Patients With Refractory or First-Relapsed Acute Myelogenous Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Study Start Date: March 2000
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00006045

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

Additional Information:
No publications provided

Study ID Numbers: CDR0000068061, PDL-195-301, MSKCC-00029, UCLA-9910050, NCI-G00-1819
Study First Received: July 5, 2000
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00006045     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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)

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Leukemia, Myeloid, Acute
Antibodies, Monoclonal
Leukemia
Sensory System Agents
Therapeutic Uses
Analgesics
Etoposide
Cytarabine
Neoplasms by Histologic Type
Leukemia, Myeloid
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Mitoxantrone
Peripheral Nervous System Agents
Antineoplastic Agents, Phytogenic
Central Nervous System Agents

ClinicalTrials.gov processed this record on November 27, 2009