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.

Condition	Treatment or Intervention	Phase
Refractory Anemia secondary myelodysplastic syndrome refractory anemia with ringed sideroblasts de novo myelodysplastic syndrome refractory anemia with excess blasts in transformation refractory cytopenia with multilineage dysplasia refractory anemia with excess blasts Chronic Myelomonocytic Leukemia	Drug: topotecan	Phase II

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  15 Years and above

Criteria

PROTOCOL ENTRY 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

--Prior/Concurrent Therapy--

• Biologic therapy: At least 1 month since prior interferon; No prior hematopoietic growth factors or cytokines except epoietin alfa; No concurrent epoietin 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

--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

Alabama
      Veterans Affairs Medical Center - Birmingham, Birmingham,  Alabama,  35233,  United States
California
      UCSF Cancer Center and Cancer Research Institute, San Francisco,  California,  94115-0128,  United States
      University of California San Diego Cancer Center, La Jolla,  California,  92093-0658,  United States
      Veterans Affairs Medical Center - San Francisco, San Francisco,  California,  94121,  United States
Delaware
      CCOP - Christiana Care Health Services, Wilmington,  Delaware,  19899,  United States
District of Columbia
      Vincent T. Lombardi Cancer Research Center, Georgetown University, Washington,  District of Columbia,  20007,  United States
      Walter Reed Army Medical Center, Washington,  District of Columbia,  20307-5000,  United States
Florida
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States
Illinois
      Louis A. Weiss Memorial Hospital, Chicago,  Illinois,  60640,  United States
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637,  United States
      University of Illinois at Chicago Health Sciences Center, Chicago,  Illinois,  60612,  United States
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States
Iowa
      University of Iowa Hospitals and Clinics, Iowa City,  Iowa,  52242,  United States
Maine
      Veterans Affairs Medical Center - Togus, Togus,  Maine,  04330,  United States
Maryland
      Marlene & Stewart Greenebaum Cancer Center, University of Maryland, Baltimore,  Maryland,  21201,  United States
Massachusetts
      Dana-Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      University of Massachusetts Memorial Medical Center, Worcester,  Massachusetts,  01655,  United States
Minnesota
      Veterans Affairs Medical Center - Minneapolis, Minneapolis,  Minnesota,  55417,  United States
Missouri
      Barnes-Jewish Hospital, Saint Louis,  Missouri,  63110,  United States
      Ellis Fischel Cancer Center - Columbia, Columbia,  Missouri,  65203,  United States
      Veterans Affairs Medical Center - Columbia (Truman Memorial), Columbia,  Missouri,  65201,  United States
Nebraska
      University of Nebraska Medical Center, Omaha,  Nebraska,  68198-3330,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Hampshire
      Norris Cotton Cancer Center, Lebanon,  New Hampshire,  03756,  United States
New York
      CCOP - North Shore University Hospital, Manhasset,  New York,  11030,  United States
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., Syracuse,  New York,  13210,  United States
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States
      Mount Sinai Medical Center, NY, New York,  New York,  10029,  United States
      New York Presbyterian Hospital - Cornell Campus, New York,  New York,  10021,  United States
      North Shore University Hospital, Manhasset,  New York,  11030,  United States
      Roswell Park Cancer Institute, Buffalo,  New York,  14263-0001,  United States
      State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States
      Veterans Affairs Medical Center - Buffalo, Buffalo,  New York,  14215,  United States
      Veterans Affairs Medical Center - Syracuse, Syracuse,  New York,  13210,  United States
North Carolina
      CCOP - Southeast Cancer Control Consortium, Winston Salem,  North Carolina,  27104-4241,  United States
      Comprehensive Cancer Center of Wake Forest University Baptist Medical Center, Winston Salem,  North Carolina,  27157-1082,  United States
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
      Veterans Affairs Medical Center - Durham, Durham,  North Carolina,  27705,  United States
Ohio
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210,  United States
Rhode Island
      Rhode Island Hospital, Providence,  Rhode Island,  02903,  United States
South Carolina
      Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States
Tennessee
      University of Tennessee, Memphis Cancer Center, Memphis,  Tennessee,  38163,  United States
      Veterans Affairs Medical Center - Memphis, Memphis,  Tennessee,  38104,  United States
Vermont
      Vermont Cancer Center, Burlington,  Vermont,  05401-3498,  United States
      Veterans Affairs Medical Center - White River Junction, White River Junction,  Vermont,  05009,  United States
Virginia
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
      Veterans Affairs Medical Center - Richmond, Richmond,  Virginia,  23249,  United States

Study chairs or principal investigators

David L. Grinblatt,  Study Chair,  Cancer and Leukemia Group B   

Study ID Numbers:  CDR0000066776; CLB-19803
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003675
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08