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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005962
• Other study ID #: CDR0000067944
• Secondary ID: E-4999
• Status: Completed
• Phase: Phase 2
• Start date: October 4, 2000
• Est. completion date: June 2007

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: June 2007
• Est. primary completion date: October 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Biological:
• sargramostim

Drug:
• cyclophosphamide

• cytarabine

• gemtuzumab ozogamicin

• liposomal daunorubicin citrate

• topotecan hydrochloride

Locations

Country	Name	City	State
Puerto Rico	MBCCOP - San Juan	San Juan
Puerto Rico	Veterans Affairs Medical Center - San Juan	San Juan
South Africa	Pretoria Academic Hospitals	Pretoria
United States	CCOP - Ann Arbor Regional	Ann Arbor	Michigan
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	New England Medical Center Hospital	Boston	Massachusetts
United States	Albert Einstein Comprehensive Cancer Center	Bronx	New York
United States	MBCCOP-Our Lady of Mercy Cancer Center	Bronx	New York
United States	Veterans Affairs Medical Center - Brooklyn	Brooklyn	New York
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	Veterans Affairs Medical Center - Lakeside Chicago	Chicago	Illinois
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Ireland Cancer Center	Cleveland	Ohio
United States	CCOP - Columbus	Columbus	Ohio
United States	CCOP - Central Illinois	Decatur	Illinois
United States	CCOP - Colorado Cancer Research Program, Inc.	Denver	Colorado
United States	CCOP - Iowa Oncology Research Association	Des Moines	Iowa
United States	Cancer Center and Beckman Research Institute, City of Hope	Duarte	California
United States	CCOP - Duluth	Duluth	Minnesota
United States	Veterans Affairs Medical Center - East Orange	East Orange	New Jersey
United States	CCOP - Evanston	Evanston	Illinois
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	Veterans Affairs Medical Center - Gainsville	Gainesville	Florida
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Indiana University Cancer Center	Indianapolis	Indiana
United States	Veterans Affairs Medical Center - Indianapolis (Roudebush)	Indianapolis	Indiana
United States	Holden Comprehensive Cancer Center at The University of Iowa	Iowa City	Iowa
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Veterans Affairs Medical Center - Madison	Madison	Wisconsin
United States	CCOP - Marshfield Medical Research and Education Foundation	Marshfield	Wisconsin
United States	Veterans Affairs Medical Center - Miami	Miami	Florida
United States	University of Minnesota Cancer Center	Minneapolis	Minnesota
United States	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota
United States	Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York
United States	Veterans Affairs Medical Center - New York	New York	New York
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Veterans Affairs Medical Center - Omaha	Omaha	Nebraska
United States	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Hahnemann University Hospital	Philadelphia	Pennsylvania
United States	Kimmel Cancer Center of Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Veterans Affairs Medical Center - Pittsburgh	Pittsburgh	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	University of Rochester Cancer Center	Rochester	New York
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	CCOP - Scottsdale Oncology Program	Scottsdale	Arizona
United States	CCOP - Sioux Community Cancer Consortium	Sioux Falls	South Dakota
United States	Stanford University Medical Center	Stanford	California
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Veterans Affairs Medical Center - Tampa (Haley)	Tampa	Florida
United States	CCOP - Toledo Community Hospital Oncology Program	Toledo	Ohio
United States	CCOP - Oklahoma	Tulsa	Oklahoma
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	CCOP - Christiana Care Health Services	Wilmington	Delaware
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Puerto Rico,  South Africa, 

References & Publications (2)

Litzow MR, Goloubeva O, Rowe J, et al.: A randomized phase II trial of gemtuzumab ozogamicin vs. liposomal daunorubicin vs. cyclophosphamide plus topotecan, each combined with intermediate dose Ara-C for the treatment of patients with relapsed or refracto

Litzow MR, Othus M, Cripe LD, Gore SD, Lazarus HM, Lee SJ, Bennett JM, Paietta EM, Dewald GW, Rowe JM, Tallman MS; Eastern Cooperative Oncology Group Leukemia Committee. Failure of three novel regimens to improve outcome for patients with relapsed or refr — View Citation