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

Sponsor

Facet Biotech (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00006045

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: lintuzumab Drug: cytarabine Drug: etoposide Drug: mitoxantrone hydrochloride	Phase 3

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 Design

Study Type:

Interventional

Primary Purpose:

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 Standardized Chemotherapy Alone in the Treatment of Patients With Refractory or First-Relapsed Acute Myelogenous Leukemia (AML)

Study Start Date :

Mar 1, 2000

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

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