Topotecan in Treating Patients With Myelodysplastic Syndrome

NCT ID: NCT00003675

Last Updated: 2016-07-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-03-31

Study Completion Date

2009-04-30

Brief Summary

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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.

PURPOSE: Randomized phase II trial to study the effectiveness of topotecan in treating patients who have myelodysplastic syndrome.

Detailed Description

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OBJECTIVES: I. Estimate complete or partial remission, hematologic improvement, and cytogenic response rate when oral topotecan is given twice a day for 5 days versus once a day for 10 days to patients with myelodysplastic syndromes. II. Evaluate the safety and toxicity of oral topotecan in these patients. III. Evaluate whether there are morphologic and/or cytogenetic subsets of the myelodysplastic syndromes that will respond optimally to this regimen. IV. Evaluate the change in the percentage of bone marrow blast cells in these patients during treatment. V. Evaluate the time to transformation to acute myeloid leukemia (AML) or death in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to FAB subtype: 1. Refractory anemia with excess blasts 2. Refractory anemia with excess blasts in transformation 3. Chronic myelomonocytic leukemia 4. Refractory anemia, refractory anemia with ringed sideroblasts, and refractory cytopenia with multilineage dysplasia Patients are randomized to receive oral topotecan either twice daily for 5 days or once daily for 10 days. Courses are repeated every 21 days. Patients are evaluated for hematologic response after the initial 2 courses, and then every 4 courses. If a partial response or hematologic improvement is observed, treatment continues until disease progression to acute myeloid leukemia, relapse, death, or irreversible toxicity. Patients who achieve a complete response receive an additional 2 courses of therapy before discontinuation of protocol treatment. Patients are followed every 3 months for 2 years, then every year for an additional 3 years, and at time of progression.

PROJECTED ACCRUAL: A total of 90 patients (45 per arm) will be accrued for this study within 13 months.

Conditions

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Leukemia Myelodysplastic Syndromes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Oral Topotecan 5 days

Patients receive intervention twice daily for 5 days

Group Type EXPERIMENTAL

topotecan hydrochloride

Intervention Type DRUG

1.2 mg/sq m twice a day for 5 days (Arm I) and once a day for 10 days (Arm II)

Oral Topotecan 10 days

Patients receive intervention once daily for 10 days

Group Type EXPERIMENTAL

topotecan hydrochloride

Intervention Type DRUG

1.2 mg/sq m twice a day for 5 days (Arm I) and once a day for 10 days (Arm II)

Interventions

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topotecan hydrochloride

1.2 mg/sq m twice a day for 5 days (Arm I) and once a day for 10 days (Arm II)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS: Primary or therapy-related myelodysplastic syndrome: Refractory anemia with excess blasts Refractory anemia with excess blasts in transformation Chronic myelomonocytic leukemia Refractory anemia, refractory anemia with ringed sideroblasts, or refractory cytopenia with multilineage dysplasia These patients must also have one of the following criteria: Greater than 4 units of RBCs transfused within the past 3 months OR Platelet count less than 50,000/mm3 OR Neutrophil count less than 1,000/mm3 AND a recent infection requiring antibiotics

PATIENT CHARACTERISTICS: Age: Over 15 Performance status: 0-2 Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 1.5 mg/dL SGOT no greater than 2 times upper limit of normal Renal: Creatinine no greater than 1.5 mg/dL Other: Not pregnant or nursing Fertile patients must use effective contraception Free of any evidence of prior cancer for at least 12 months

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 1 month since prior interferon No prior hematopoietic growth factors or cytokines except epoetin alfa No concurrent epoetin alfa Chemotherapy: No prior topotecan No prior chemotherapy for this disease At least 12 months since prior chemotherapy for another disease No other concurrent chemotherapy Endocrine therapy: At least 1 month since prior corticosteroids No concurrent hormonal therapy for disease-related conditions Concurrent steroids for adrenal failure allowed No concurrent dexamethasone and other steroidal antiemetics Radiotherapy: No prior radiotherapy for this disease At least 12 months since prior radiotherapy for another disease Surgery: Not specified Other: No prior cytotoxic therapy (including low-dose antimetabolites) for this disease At least 1 month since prior retinoids
Minimum Eligible Age

15 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David L. Grinblatt, MD

Role: STUDY_CHAIR

Louis A. Weiss Memorial Hospital

Locations

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Veterans Affairs Medical Center - Birmingham

Birmingham, Alabama, United States

Site Status

University of California San Diego Cancer Center

La Jolla, California, United States

Site Status

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Site Status

Veterans Affairs Medical Center - San Francisco

San Francisco, California, United States

Site Status

CCOP - Christiana Care Health Services

Wilmington, Delaware, United States

Site Status

Vincent T. Lombardi Cancer Research Center, Georgetown University

Washington D.C., District of Columbia, United States

Site Status

Walter Reed Army Medical Center

Washington D.C., District of Columbia, United States

Site Status

CCOP - Mount Sinai Medical Center

Miami Beach, Florida, United States

Site Status

University of Illinois at Chicago Health Sciences Center

Chicago, Illinois, United States

Site Status

Veterans Affairs Medical Center - Chicago (Westside Hospital)

Chicago, Illinois, United States

Site Status

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Site Status

Louis A. Weiss Memorial Hospital

Chicago, Illinois, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

Veterans Affairs Medical Center - Togus

Togus, Maine, United States

Site Status

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

University of Massachusetts Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

Veterans Affairs Medical Center - Minneapolis

Minneapolis, Minnesota, United States

Site Status

Veterans Affairs Medical Center - Columbia (Truman Memorial)

Columbia, Missouri, United States

Site Status

Ellis Fischel Cancer Center - Columbia

Columbia, Missouri, United States

Site Status

Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

CCOP - Southern Nevada Cancer Research Foundation

Las Vegas, Nevada, United States

Site Status

Norris Cotton Cancer Center

Lebanon, New Hampshire, United States

Site Status

Veterans Affairs Medical Center - Buffalo

Buffalo, New York, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

CCOP - North Shore University Hospital

Manhasset, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

New York Presbyterian Hospital - Cornell Campus

New York, New York, United States

Site Status

Mount Sinai Medical Center, NY

New York, New York, United States

Site Status

CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.

Syracuse, New York, United States

Site Status

State University of New York - Upstate Medical University

Syracuse, New York, United States

Site Status

Veterans Affairs Medical Center - Syracuse

Syracuse, New York, United States

Site Status

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, United States

Site Status

Veterans Affairs Medical Center - Durham

Durham, North Carolina, United States

Site Status

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Site Status

CCOP - Southeast Cancer Control Consortium

Winston-Salem, North Carolina, United States

Site Status

Comprehensive Cancer Center of Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status

Arthur G. James Cancer Hospital - Ohio State University

Columbus, Ohio, United States

Site Status

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Veterans Affairs Medical Center - Memphis

Memphis, Tennessee, United States

Site Status

University of Tennessee, Memphis Cancer Center

Memphis, Tennessee, United States

Site Status

Vermont Cancer Center

Burlington, Vermont, United States

Site Status

Veterans Affairs Medical Center - White River Junction

White River Junction, Vermont, United States

Site Status

Veterans Affairs Medical Center - Richmond

Richmond, Virginia, United States

Site Status

MBCCOP - Massey Cancer Center

Richmond, Virginia, United States

Site Status

Countries

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United States

References

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Klein CE, Kastrissios H, Miller AA, Hollis D, Yu D, Rosner GL, Grinblatt DL, Larson RA, Ratain MJ. Pharmacokinetics, pharmacodynamics and adherence to oral topotecan in myelodysplastic syndromes: a Cancer and Leukemia Group B study. Cancer Chemother Pharmacol. 2006 Jan;57(2):199-206. doi: 10.1007/s00280-005-0023-6. Epub 2005 Sep 13.

Reference Type RESULT
PMID: 16158312 (View on PubMed)

Grinblatt DL, Yu D, Hars V, et al.: Relationships of response to oral topotecan (Topo) for myelodysplastic syndrome (MDS) with IPSS group and cytogenetics - CALGB study 19803. [Abstract] Blood 100 (11 Pt 1): A-3137, 2002.

Reference Type RESULT

Grinblatt DL, Yu D, Klein C, et al.: Two schedules of oral topotecan for myelodysplastic syndrome (MDS)-CALGB study 19803. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1209, 2001.

Reference Type RESULT

Other Identifiers

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U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CLB-19803

Identifier Type: -

Identifier Source: secondary_id

CDR0000066776

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-19803

Identifier Type: -

Identifier Source: org_study_id

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