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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)


Phase 2
15 Years
N/A
Not Enrolling
Both
Leukemia, Myelodysplastic Syndromes

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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 InstituteBuffalo, New York  14263
Memorial Sloan-Kettering Cancer CenterNew York, New York  10021
Vincent T. Lombardi Cancer Research Center, Georgetown UniversityWashington, District of Columbia  20007
Walter Reed Army Medical CenterWashington, District of Columbia  20307-5000
University of Chicago Cancer Research CenterChicago, Illinois  60637
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
University of Massachusetts Memorial Medical CenterWorcester, Massachusetts  01655
Lineberger Comprehensive Cancer Center, UNCChapel Hill, North Carolina  27599-7295
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Comprehensive Cancer Center of Wake Forest University Baptist Medical CenterWinston-Salem, North Carolina  27157-1082
Arthur G. James Cancer Hospital - Ohio State UniversityColumbus, Ohio  43210
Medical University of South CarolinaCharleston, South Carolina  29425-0721
Rhode Island HospitalProvidence, Rhode Island  02903
Vermont Cancer CenterBurlington, Vermont  05401-3498
CCOP - Southern Nevada Cancer Research FoundationLas Vegas, Nevada  89106
University of California San Diego Cancer CenterLa Jolla, California  92093-0658
UCSF Cancer Center and Cancer Research InstituteSan Francisco, California  94115-0128
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - Mount Sinai Medical CenterMiami Beach, Florida  33140
Marlene & Stewart Greenebaum Cancer Center, University of MarylandBaltimore, Maryland  21201
Ellis Fischel Cancer Center - ColumbiaColumbia, Missouri  65203
Barnes-Jewish HospitalSaint Louis, Missouri  63110
Norris Cotton Cancer CenterLebanon, New Hampshire  03756
CCOP - North Shore University HospitalManhasset, New York  11030
State University of New York - Upstate Medical UniversitySyracuse, New York  13210
CCOP - Southeast Cancer Control ConsortiumWinston-Salem, North Carolina  27104-4241
University of Tennessee, Memphis Cancer CenterMemphis, Tennessee  38103
MBCCOP - Massey Cancer CenterRichmond, Virginia  23298-0037
Mount Sinai Medical Center, NYNew York, New York  10029
New York Presbyterian Hospital - Cornell CampusNew York, New York  10021
Veterans Affairs Medical Center - BirminghamBirmingham, Alabama  35233
Veterans Affairs Medical Center - White River JunctionWhite River Junction, Vermont  05009
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
North Shore University HospitalManhasset, New York  11030
Veterans Affairs Medical Center - Chicago (Westside Hospital)Chicago, Illinois  60612
Veterans Affairs Medical Center - San FranciscoSan Francisco, California  94121
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.Syracuse, New York  13217
Veterans Affairs Medical Center - MemphisMemphis, Tennessee  38104
Veterans Affairs Medical Center - RichmondRichmond, Virginia  23249
University of Illinois at Chicago Health Sciences CenterChicago, Illinois  60612
Veterans Affairs Medical Center - TogusTogus, Maine  04330
Veterans Affairs Medical Center - MinneapolisMinneapolis, Minnesota  55417
Veterans Affairs Medical Center - Columbia (Truman Memorial)Columbia, Missouri  65201
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330
Veterans Affairs Medical Center - BuffaloBuffalo, New York  14215
Veterans Affairs Medical Center - SyracuseSyracuse, New York  13210
Veterans Affairs Medical Center - DurhamDurham, North Carolina  27705
Louis A. Weiss Memorial HospitalChicago, Illinois  60640