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)
15 Years
N/A
Both
Leukemia, Myelodysplastic Syndromes
Trial Information
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)
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response
Outcome Description:
Response in the peripheral blood is assessed during tx, q 3 mon for 2 yrs post tx, then annually for another 3 years, and then at progression Bone marrow response is assessed prior to cycle 3, then q 4 cycles for the 1st yr. then q 8 cycles for patients who continue beyond
Outcome Time Frame:
During treatment and up to progression post treatment
Safety Issue:
No
Principal Investigator
David L. Grinblatt, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Louis A. Weiss Memorial Hospital
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000066776
NCT ID:
NCT00003675
Start Date:
March 1999
Completion Date:
April 2009
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- 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
- Leukemia
- Myelodysplastic Syndromes
- Preleukemia
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| Vincent T. Lombardi Cancer Research Center, Georgetown University | Washington, District of Columbia 20007 |
| Walter Reed Army Medical Center | Washington, District of Columbia 20307-5000 |
| University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
| University of Iowa Hospitals and Clinics | Iowa City, Iowa 52242 |
| University of Massachusetts Memorial Medical Center | Worcester, Massachusetts 01655 |
| Lineberger Comprehensive Cancer Center, UNC | Chapel Hill, North Carolina 27599-7295 |
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| Comprehensive Cancer Center of Wake Forest University Baptist Medical Center | Winston-Salem, North Carolina 27157-1082 |
| Arthur G. James Cancer Hospital - Ohio State University | Columbus, Ohio 43210 |
| Medical University of South Carolina | Charleston, South Carolina 29425-0721 |
| Rhode Island Hospital | Providence, Rhode Island 02903 |
| Vermont Cancer Center | Burlington, Vermont 05401-3498 |
| CCOP - Southern Nevada Cancer Research Foundation | Las Vegas, Nevada 89106 |
| University of California San Diego Cancer Center | La Jolla, California 92093-0658 |
| UCSF Cancer Center and Cancer Research Institute | San Francisco, California 94115-0128 |
| CCOP - Christiana Care Health Services | Wilmington, Delaware 19899 |
| CCOP - Mount Sinai Medical Center | Miami Beach, Florida 33140 |
| Marlene & Stewart Greenebaum Cancer Center, University of Maryland | Baltimore, Maryland 21201 |
| Ellis Fischel Cancer Center - Columbia | Columbia, Missouri 65203 |
| Barnes-Jewish Hospital | Saint Louis, Missouri 63110 |
| Norris Cotton Cancer Center | Lebanon, New Hampshire 03756 |
| CCOP - North Shore University Hospital | Manhasset, New York 11030 |
| State University of New York - Upstate Medical University | Syracuse, New York 13210 |
| CCOP - Southeast Cancer Control Consortium | Winston-Salem, North Carolina 27104-4241 |
| University of Tennessee, Memphis Cancer Center | Memphis, Tennessee 38103 |
| MBCCOP - Massey Cancer Center | Richmond, Virginia 23298-0037 |
| Mount Sinai Medical Center, NY | New York, New York 10029 |
| New York Presbyterian Hospital - Cornell Campus | New York, New York 10021 |
| Veterans Affairs Medical Center - Birmingham | Birmingham, Alabama 35233 |
| Veterans Affairs Medical Center - White River Junction | White River Junction, Vermont 05009 |
| Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
| North Shore University Hospital | Manhasset, New York 11030 |
| Veterans Affairs Medical Center - Chicago (Westside Hospital) | Chicago, Illinois 60612 |
| Veterans Affairs Medical Center - San Francisco | San Francisco, California 94121 |
| CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C. | Syracuse, New York 13217 |
| Veterans Affairs Medical Center - Memphis | Memphis, Tennessee 38104 |
| Veterans Affairs Medical Center - Richmond | Richmond, Virginia 23249 |
| University of Illinois at Chicago Health Sciences Center | Chicago, Illinois 60612 |
| Veterans Affairs Medical Center - Togus | Togus, Maine 04330 |
| Veterans Affairs Medical Center - Minneapolis | Minneapolis, Minnesota 55417 |
| Veterans Affairs Medical Center - Columbia (Truman Memorial) | Columbia, Missouri 65201 |
| University of Nebraska Medical Center | Omaha, Nebraska 68198-3330 |
| Veterans Affairs Medical Center - Buffalo | Buffalo, New York 14215 |
| Veterans Affairs Medical Center - Syracuse | Syracuse, New York 13210 |
| Veterans Affairs Medical Center - Durham | Durham, North Carolina 27705 |
| Louis A. Weiss Memorial Hospital | Chicago, Illinois 60640 |
