Clinical trial NCT00003675: Topotecan in Treating Patients With Myelodysplastic Syndrome
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Myelodysplastic Syndromes
Keywords: 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
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-07-22
Enrollment: 100
Sex: ALL
Minimum age (years): 15
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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 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

Primary outcomes:
measure: Response
timeFrame: During treatment and up to progression post treatment
measure: Toxicity
timeFrame: during treatment until progression
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Veterans Affairs Medical Center - Birmingham
state: Alabama
city: La Jolla
country: United States
facility: University of California San Diego Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Cancer Center and Cancer Research Institute
state: California
city: San Francisco
country: United States
facility: Veterans Affairs Medical Center - San Francisco
state: California
city: Wilmington
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Vincent T. Lombardi Cancer Research Center, Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Chicago
country: United States
facility: University of Illinois at Chicago Health Sciences Center
state: Illinois
city: Chicago
country: United States
facility: Veterans Affairs Medical Center - Chicago (Westside Hospital)
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Chicago
country: United States
facility: Louis A. Weiss Memorial Hospital
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Togus
country: United States
facility: Veterans Affairs Medical Center - Togus
state: Maine
city: Baltimore
country: United States
facility: Marlene & Stewart Greenebaum Cancer Center, University of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Memorial Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Columbia
country: United States
facility: Veterans Affairs Medical Center - Columbia (Truman Memorial)
state: Missouri
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center - Columbia
state: Missouri
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: CCOP - Southern Nevada Cancer Research Foundation
state: Nevada
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center
state: New Hampshire
city: Buffalo
country: United States
facility: Veterans Affairs Medical Center - Buffalo
state: New York
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Manhasset
country: United States
facility: CCOP - North Shore University Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital - Cornell Campus
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center, NY
state: New York
city: Syracuse
country: United States
facility: CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
state: New York
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Syracuse
country: United States
facility: Veterans Affairs Medical Center - Syracuse
state: New York
city: Chapel Hill
country: United States
facility: Lineberger Comprehensive Cancer Center, UNC
state: North Carolina
city: Durham
country: United States
facility: Veterans Affairs Medical Center - Durham
state: North Carolina
city: Durham
country: United States
facility: Duke Comprehensive Cancer Center
state: North Carolina
city: Winston-Salem
country: United States
facility: CCOP - Southeast Cancer Control Consortium
state: North Carolina
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital - Ohio State University
state: Ohio
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Veterans Affairs Medical Center - Memphis
state: Tennessee
city: Memphis
country: United States
facility: University of Tennessee, Memphis Cancer Center
state: Tennessee
city: Burlington
country: United States
facility: Vermont Cancer Center
state: Vermont
city: White River Junction
country: United States
facility: Veterans Affairs Medical Center - White River Junction
state: Vermont
city: Richmond
country: United States
facility: Veterans Affairs Medical Center - Richmond
state: Virginia
city: Richmond
country: United States
facility: MBCCOP - Massey Cancer Center
state: Virginia
Study officials:
affiliation: Louis A. Weiss Memorial Hospital
name: David L. Grinblatt, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.