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

Primary Purpose

Leukemia

Status
Unknown status
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
lintuzumab
cytarabine
etoposide
mitoxantrone hydrochloride
Sponsored by
Facet Biotech
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • USC/Norris Comprehensive Cancer Center
  • Jonsson Comprehensive Cancer Center, UCLA
  • Beckman Research Institute, City of Hope
  • St. Joseph Hospital - Orange
  • Sutter Cancer Center
  • University of California Davis Cancer Center
  • Sidney Kimmel Cancer Center
  • Washington Cancer Institute
  • Emory Clinic
  • University of Illinois at Chicago
  • Loyola University Medical Center
  • University of Iowa Hospitals and Clinics
  • Louisiana State University School of Medicine
  • Johns Hopkins Oncology Center
  • New England Medical Center Hospital
  • Massachusetts General Hospital Cancer Center
  • Dana-Farber Cancer Institute
  • Beth Israel Deaconess Medical Center
  • West Michigan Cancer Center
  • North Mississippi Hematology and Oncology Associates, Ltd.
  • Washington University Barnard Cancer Center
  • Nevada Cancer Center
  • Cancer Institute of New Jersey
  • Albert Einstein Comprehensive Cancer Center
  • Roswell Park Cancer Institute
  • North Shore University Hospital
  • Memorial Sloan-Kettering Cancer Center
  • New York Presbyterian Hospital - Cornell Campus
  • New York Medical College
  • Lineberger Comprehensive Cancer Center, UNC
  • Duke Comprehensive Cancer Center
  • Akron General Medical Center
  • Ireland Cancer Center
  • Cleveland Clinic Taussig Cancer Center
  • Milton S. Hershey Medical Center
  • University of Pennsylvania Cancer Center
  • University of Pittsburgh Medical Center
  • West Clinic, P.C.
  • Vanderbilt University Medical Center
  • Medical College of Wisconsin
  • Algemeen Ziekenhuis Middelheim
  • Institut Jules Bordet
  • U.Z. Gasthuisberg
  • Cross Cancer Institute
  • Health Sciences Centre
  • Queen Elizabeth II Health Science Center
  • Princess Margaret Hospital
  • Centre Hospitalier Regional et Universitaire d'Angers
  • CHRU de Nancy - Hopitaux de Brabois
  • Universitaetsklinikum Benjamin Franklin
  • Klinikum der J.W. Goethe Universitaet
  • Klinikum Rechts Der Isar/Technische Universitaet Muenchen
  • Westfaelische Wilhelms-Universitaet
  • University of Rostock
  • Academisch Medisch Centrum
  • Addenbrooke's NHS Trust
  • Royal Free Hospital
  • Leeds Teaching Hospital Trust
  • Christie Hospital N.H.S. Trust

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
July 5, 2000
Last Updated
November 5, 2013
Sponsor
Facet Biotech
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00006045
Brief Title
Combination Chemotherapy With or Without Monoclonal Antibody Therapy in Treating Patients With Refractory or Relapsed Acute Myelogenous Leukemia
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 Standardized Chemotherapy Alone in the Treatment of Patients With Refractory or First-Relapsed Acute Myelogenous Leukemia (AML)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2010
Overall Recruitment Status
Unknown status
Study Start Date
March 2000 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Facet Biotech
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
Keywords
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
lintuzumab
Intervention Type
Drug
Intervention Name(s)
cytarabine
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Type
Drug
Intervention Name(s)
mitoxantrone hydrochloride

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel Levitt, MD, PhD
Organizational Affiliation
Facet Biotech
Official's Role
Study Chair
Facility Information:
Facility Name
USC/Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033-0800
Country
United States
Facility Name
Jonsson Comprehensive Cancer Center, UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1781
Country
United States
Facility Name
Beckman Research Institute, City of Hope
City
Los Angeles
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
St. Joseph Hospital - Orange
City
Orange
State/Province
California
ZIP/Postal Code
92613-5600
Country
United States
Facility Name
Sutter Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
University of California Davis Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Sidney Kimmel Cancer Center
City
San Diego
State/Province
California
ZIP/Postal Code
92121
Country
United States
Facility Name
Washington Cancer Institute
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Emory Clinic
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
University of Iowa Hospitals and Clinics
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Louisiana State University School of Medicine
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71130-3932
Country
United States
Facility Name
Johns Hopkins Oncology Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21231
Country
United States
Facility Name
New England Medical Center Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
Massachusetts General Hospital Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
West Michigan Cancer Center
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49007
Country
United States
Facility Name
North Mississippi Hematology and Oncology Associates, Ltd.
City
Tupelo
State/Province
Mississippi
ZIP/Postal Code
38801
Country
United States
Facility Name
Washington University Barnard Cancer Center
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Nevada Cancer Center
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
Facility Name
Cancer Institute of New Jersey
City
New Brunswick
State/Province
New Jersey
ZIP/Postal Code
08901
Country
United States
Facility Name
Albert Einstein Comprehensive Cancer Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States
Facility Name
North Shore University Hospital
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
New York Presbyterian Hospital - Cornell Campus
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Lineberger Comprehensive Cancer Center, UNC
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7295
Country
United States
Facility Name
Duke Comprehensive Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Akron General Medical Center
City
Akron
State/Province
Ohio
ZIP/Postal Code
44302
Country
United States
Facility Name
Ireland Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5065
Country
United States
Facility Name
Cleveland Clinic Taussig Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Milton S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
University of Pennsylvania Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
West Clinic, P.C.
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38117
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-2516
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Algemeen Ziekenhuis Middelheim
City
Antwerp
ZIP/Postal Code
2020
Country
Belgium
Facility Name
Institut Jules Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
U.Z. Gasthuisberg
City
Leuven
ZIP/Postal Code
B-3000
Country
Belgium
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
Health Sciences Centre
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3A 1R9
Country
Canada
Facility Name
Queen Elizabeth II Health Science Center
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 2Y9
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Centre Hospitalier Regional et Universitaire d'Angers
City
Angers
ZIP/Postal Code
49033
Country
France
Facility Name
CHRU de Nancy - Hopitaux de Brabois
City
Vandoeuvre-Les-Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
Universitaetsklinikum Benjamin Franklin
City
Berlin
ZIP/Postal Code
D-12200
Country
Germany
Facility Name
Klinikum der J.W. Goethe Universitaet
City
Frankfurt
ZIP/Postal Code
D-60590
Country
Germany
Facility Name
Klinikum Rechts Der Isar/Technische Universitaet Muenchen
City
Munich
ZIP/Postal Code
D-81675
Country
Germany
Facility Name
Westfaelische Wilhelms-Universitaet
City
Munster
ZIP/Postal Code
DOH-4-8149
Country
Germany
Facility Name
University of Rostock
City
Rostock
ZIP/Postal Code
18057
Country
Germany
Facility Name
Academisch Medisch Centrum
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Facility Name
Addenbrooke's NHS Trust
City
Cambridge
State/Province
England
ZIP/Postal Code
CB2 2QQ
Country
United Kingdom
Facility Name
Royal Free Hospital
City
Hampstead, London
State/Province
England
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Leeds Teaching Hospital Trust
City
Leeds
State/Province
England
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
Facility Name
Christie Hospital N.H.S. Trust
City
Manchester
State/Province
England
ZIP/Postal Code
M20 4BX
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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

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