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Topotecan in Treating Patients With Myelodysplastic Syndrome
This study has been completed.
Sponsors and Collaborators: Cancer and Leukemia Group B
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003675
  Purpose

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 Intervention Phase
Leukemia
Myelodysplastic Syndromes
Drug: topotecan hydrochloride
Phase II

MedlinePlus related topics: Anemia Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood
Drug Information available for: Topotecan hydrochloride Topotecan
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized
Official Title: A Randomized Phase II Trial of Oral Topotecan Given Twice a Day for 5 Days or Once a Day for 10 Days to Patients With Myelodysplastic Syndromes (MDS)

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 90
Study Start Date: March 1999
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003675

  Show 48 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: David L. Grinblatt, MD Louis A. Weiss Memorial Hospital
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Publications of Results:
Grinblatt DL, Yu D, Hars V, Vardiman JW, Powell BL, Nattam S, Silverman LR, de Castro C 3rd, Stone RM, Bloomfield CD, Larson RA; for the Cancer and Leukemia Group BThe following institutions participated in this study: Dana‐Farber Cancer Institute, Boston, Mass (Eric P. Winer, MD; supported by CA32291); Dartmouth Medical School‐Norris Cotton Cancer Center, Lebanon, NH (Marc S. Ernstoff, MD; supported by CA04326); Duke University Medical Center, Durham, NC (Jeffrey Crawford, MD; supported by CA47577); Greenville Clinical Cooperative Oncology Program, Cancer Centers of the Carolinas, Greenville, SC (Jeffrey K. Giguere, MD; supported by CA29165); Illinois Oncology Research Association, Peoria, Ill (John W. Kugler, MD; supported by CA35113); Massachusetts General Hospital, Boston, Mass (Michael L. Grossbard, MD; supported by CA12449); Mount Sinai School of Medicine, New York, NY (Lewis R. Silverman, MD; supported by CA04457); Roswell Park Cancer Institute, Buffalo, NY (Ellis Levine, MD; supported by CA02599); State University of New York Upstate Medical University, Syracuse, NY (Stephen L. Graziano, MD; supported by CA21060); Ohio State University Medical Center, Columbus, Ohio (Clara D. Bloomfield, MD; supported by CA77658); University of California at San Diego, San Diego, Calif (Joanne Mortimer, MD; supported by CA11789); University of Chicago, Chicago, Ill (Gini Fleming, MD; supported by CA41287); University of Illinois Minority‐Based Clinical Cooperative Oncology Program, Chicago, Ill (Lawrence E. Feldman, MD; supported by CA74811); University of Iowa, Iowa City, Iowa (Gerald Clamon, MD; supported by CA47642); University of Maryland Greenebaum Cancer Center, Baltimore, Md (Martin Edelman, MD; supported by CA31983); University of Minnesota, Minneapolis, Minn (Bruce A. Peterson, MD; supported by CA16450); University of Missouri/Ellis Fischel Cancer Center, Columbia, Mo (Michael C. Perry, MD; supported by CA12046); University of North Carolina at Chapel Hill, Chapel Hill, NC (Thomas C. Shea, MD; supported by CA47559); University of Tennessee Memphis, Memphis, Tenn (Harvey B. Niell, MD; supported by CA47555); Wake Forest University School of Medicine, Winston‐Salem, NC (David D. Hurd, MD; supported by CA03927); and Weill Medical College of Cornell University, New York, NY (Scott Wadler, MD; supported by CA07968).. Treatment of myelodysplastic syndrome with 2 schedules and doses of oral topotecan: a Randomized Phase 2 Trial by the Cancer and Leukemia Group B (CALGB 19803). Cancer. 2008 Nov 24; [Epub ahead of print]
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. Epub 2005 Sep 13.
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.
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.

Study ID Numbers: CDR0000066776, CLB-19803
Study First Received: November 1, 1999
Last Updated: December 4, 2008
ClinicalTrials.gov Identifier: NCT00003675  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
refractory anemia
refractory anemia with ringed sideroblasts
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes
refractory cytopenia with multilineage dysplasia
childhood myelodysplastic syndromes

Study placed in the following topic categories:
Myelodysplastic syndromes
Precancerous Conditions
Chronic myelomonocytic leukemia
Refractory anemia
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Myelodysplasia
Anemia
Leukemia
Preleukemia
Anemia, Refractory
Neoplasm Metastasis
Anemia, Refractory, with Excess of Blasts
Topotecan
Bone Marrow Diseases

Additional relevant MeSH terms:
Neoplasms
Pathologic Processes
Disease
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Syndrome
Enzyme Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009