Comparison of Three Treatment Regimens in Treating Patients With Relapsed or Refractory Acute Myelogenous Leukemia

Sponsor

Eastern Cooperative Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00005962

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies such as gemtuzumab ozogamicin can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining more than one drug or combining monoclonal antibody with chemotherapy may kill more cancer cells. It is not yet known which treatment regimen is more effective for acute myelogenous leukemia.

PURPOSE: Randomized phase II trial to compare the effectiveness of three treatment regimens in treating patients who have relapsed or refractory acute myelogenous leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: sargramostim Drug: cyclophosphamide Drug: cytarabine Drug: gemtuzumab ozogamicin Drug: liposomal daunorubicin citrate Drug: topotecan hydrochloride	Phase 2

Detailed Description

OBJECTIVES:

Compare the rates of complete response (CR) and CR without full platelet recovery in patients with relapsed or refractory acute myelogenous leukemia treated with gemtuzumab ozogamicin and cytarabine vs daunorubicin liposomal and cytarabine vs cyclophosphamide, cytarabine, and topotecan.
Compare the toxicities of these 3 regimens in these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified by disease status (relapse less than 6 months after first complete response (CR) vs relapse 6-12 months after first CR vs refractory to conventional initial induction chemotherapy (no more than 2 courses) or first reinduction (no more than 1 course) vs second or greater relapse).

Induction: Patients are randomized to 1 of 3 treatment arms:
Arm I: Patients receive cytarabine IV over 2 hours on days 1-4 and gemtuzumab ozogamicin IV over 2 hours on day 5.
Arm II: Patients receive daunorubicin liposomal IV over a minimum of 2 hours on days 1-3 and cytarabine IV over 2 hours (beginning immediately after completion of daunorubicin liposomal infusion) on days 1-4.
Arm III: Patients receive cyclophosphamide IV over 1 hour every 12 hours on days 1-3, cytarabine IV over 2 hours (beginning immediately after completion of cyclophosphamide infusion) on days 2-6, and topotecan IV continuously on days 2-6.
Consolidation: Patients who achieve complete remission (CR) receive 1 additional course of induction therapy on the same arm to which they were originally randomized beginning within 4-6 weeks after initial documentation of CR. Patients on arm II receive no additional daunorubicin liposomal if resting ejection fraction is less than 50% preconsolidation. All patients receive sargramostim (GM-CSF) IV over 4 hours or SQ daily beginning 24 hours after completion of consolidation therapy and continuing until blood counts recover.

Patients are followed every 3 months through year 2, every 6 months through year 5, and then annually thereafter until death.

PROJECTED ACCRUAL: A maximum of 150-165 patients (50-55 per arm) will be accrued for this study within 2 years.

Study Design

Study Type:

Interventional

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

A Phase II Randomized Trial of Immunologic and Chemotherapeutic Agents for Treatment of Patients With Relapsed or Refractory Acute Myelogenous Leukemia

Study Start Date :

Jul 1, 2000

Actual Primary Completion Date :

Oct 1, 2005

Actual Study Completion Date :

Jun 1, 2007

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 of one of the following types:
Acute myeloblastic leukemia (FAB type M0, M1, or M2)
Acute promyelocytic leukemia (FAB type M3) allowed if ineligible for an ECOG M3 protocol or if no tretinoin or arsenic trioxide therapy is planned
Acute myelomonocytic leukemia (FAB type M4)
Acute monocytic leukemia (FAB type M5)
Acute erythroleukemia (FAB type M6)
Acute megakaryocytic leukemia (FAB type M7)
Must meet 1 of the following criteria:
Relapse less than 6 months after first complete remission (CR)
Relapse 6-12 months after first CR
Refractory to conventional initial induction chemotherapy (no more than 2 courses) or first reinduction (no more than 1 course)
Must have marrow documentation of residual leukemia after chemotherapy (for at least 2 weeks duration)
Second or greater relapse
No relapse greater than 1 year after achieving first CR
Blast cells must be CD33 positive
Prior CNS leukemia allowed if there is currently documentation of no CNS involvement on CSF examination (i.e., negative CSF by lumbar puncture)

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

See Disease Characteristics

Hepatic:

Bilirubin no greater than 2.0 mg/dL*
SGOT less than 2 times upper limit of normal* NOTE: *Unless due to leukemia infiltration

Renal:

Creatinine no greater than 2.0 mg/dL

Cardiovascular:

See Chemotherapy
No myocardial infarction within the past 3 months
No significant congestive heart failure
No significant cardiac arrhythmia
Cardiac ejection fraction normal by MUGA scan or echocardiogram
Resting ejection fraction at least 50% or at least 5% increase with exercise
Shortening fraction at least 24% or normal by echocardiogram

Other:

Not pregnant or nursing
Fertile patients must use effective contraception
No concurrent organ damage or other medical problems that would precludestudy therapy
No concurrent evidence (including positive blood or deep tissue cultures or stains) of invasive fungal infection
No hypersensitivity to ingredients of gemtuzumab ozogamicin or daunorubicin liposomal
No other active tumor that would interfere with study therapy or increase risk

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No prior gemtuzumab ozogamicin

Chemotherapy:

See Disease Characteristics
See Biologic therapy
No prior daunorubicin liposomal or topotecan
Prior doxorubicin (no greater than 300 mg/m2), daunorubicin (no greater than 300 mg/m2), idarubicin (no greater than 100 mg/m2), or mitoxantrone (no greater than 100 mg/m2) allowed if left ventricular function is adequate
At least 4 weeks since prior chemotherapy except patients who are refractory to conventional initial induction chemotherapy
Prior hydroxyurea allowed within 4 weeks prior to beginning study
Hydroxyurea must be discontinued at least 24 hours prior to beginning study

Endocrine therapy:

Not specified

Radiotherapy:

At least 4 weeks since prior radiotherapy except patients who are refractory to conventional initial induction chemotherapy

Surgery:

Not specified

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CCOP - Scottsdale Oncology Program	Scottsdale	Arizona	United States	85259-5404
2	Cancer Center and Beckman Research Institute, City of Hope	Duarte	California	United States	91010-3000
3	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California	United States	94304
4	Stanford University Medical Center	Stanford	California	United States	94305-5408
5	CCOP - Colorado Cancer Research Program, Inc.	Denver	Colorado	United States	80209-5031
6	CCOP - Christiana Care Health Services	Wilmington	Delaware	United States	19899
7	Veterans Affairs Medical Center - Gainsville	Gainesville	Florida	United States	32608-1197
8	Veterans Affairs Medical Center - Miami	Miami	Florida	United States	33125
9	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612-9497
10	Veterans Affairs Medical Center - Tampa (Haley)	Tampa	Florida	United States	33612
11	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois	United States	60611-3013
12	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois	United States	60611
13	CCOP - Central Illinois	Decatur	Illinois	United States	62526
14	CCOP - Evanston	Evanston	Illinois	United States	60201
15	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61602
16	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
17	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202-5289
18	Veterans Affairs Medical Center - Indianapolis (Roudebush)	Indianapolis	Indiana	United States	46202
19	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa	United States	52403-1206
20	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309-1016
21	Holden Comprehensive Cancer Center at The University of Iowa	Iowa City	Iowa	United States	52242-1009
22	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
23	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
24	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
25	New England Medical Center Hospital	Boston	Massachusetts	United States	02111
26	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
27	CCOP - Ann Arbor Regional	Ann Arbor	Michigan	United States	48106
28	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49007-3731
29	CCOP - Duluth	Duluth	Minnesota	United States	55805
30	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55417
31	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
32	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
33	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
34	Veterans Affairs Medical Center - Omaha	Omaha	Nebraska	United States	68105
35	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68131
36	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
37	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey	United States	07018-1095
38	CCOP - Northern New Jersey	Hackensack	New Jersey	United States	07601
39	Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08901
40	Albert Einstein Comprehensive Cancer Center	Bronx	New York	United States	10461
41	MBCCOP-Our Lady of Mercy Cancer Center	Bronx	New York	United States	10466
42	Veterans Affairs Medical Center - Brooklyn	Brooklyn	New York	United States	11209
43	Veterans Affairs Medical Center - New York	New York	New York	United States	10010
44	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York	United States	10016
45	University of Rochester Cancer Center	Rochester	New York	United States	14642
46	CCOP - Merit Care Hospital	Fargo	North Dakota	United States	58122
47	Ireland Cancer Center	Cleveland	Ohio	United States	44106-5065
48	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
49	CCOP - Columbus	Columbus	Ohio	United States	43206
50	CCOP - Toledo Community Hospital Oncology Program	Toledo	Ohio	United States	43623-3456
51	CCOP - Oklahoma	Tulsa	Oklahoma	United States	74136
52	Hahnemann University Hospital	Philadelphia	Pennsylvania	United States	19102-1192
53	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania	United States	19104-4283
54	Kimmel Cancer Center of Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
55	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
56	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15213-3489
57	Veterans Affairs Medical Center - Pittsburgh	Pittsburgh	Pennsylvania	United States	15240
58	CCOP - MainLine Health	Wynnewood	Pennsylvania	United States	19096
59	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota	United States	57104
60	Veterans Affairs Medical Center - Madison	Madison	Wisconsin	United States	53705
61	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
62	CCOP - Marshfield Medical Research and Education Foundation	Marshfield	Wisconsin	United States	54449
63	MBCCOP - San Juan	San Juan		Puerto Rico	00927-5800
64	Veterans Affairs Medical Center - San Juan	San Juan		Puerto Rico	00927-5800
65	Pretoria Academic Hospitals	Pretoria		South Africa	0001