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Fludarabine, Carboplatin, and Topotecan in Treating Patients With Relapsed or Refractory Acute Leukemia or Advanced Myelodysplastic Syndrome

This study is ongoing, but not recruiting participants.

Sponsors and Collaborators: Ireland Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005593
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of fludarabine, carboplatin, and topotecan in treating patients who have relapsed or refractory acute leukemia or advanced myelodysplastic syndrome.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Drug: carboplatin
Drug: fludarabine phosphate
Drug: topotecan hydrochloride
Phase I

MedlinePlus related topics:   Cancer    Leukemia, Adult Acute    Leukemia, Adult Chronic    Leukemia, Childhood   

Drug Information available for:   Carboplatin    Fludarabine    Fludarabine monophosphate    Topotecan hydrochloride    Topotecan   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment
Official Title:   Phase I Study of Fludarabine, Carboplatin, and Topotecan for Patients With Relapsed/Refractory Acute Leukemia and Advanced Myelodysplastic Syndromes

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

Study Start Date:   September 1998

Detailed Description:

OBJECTIVES: I. Determine the maximum tolerated dose of topotecan when administered with carboplatin and fludarabine in patients with refractory or relapsed acute leukemia or advanced myelodysplastic syndrome. II. Determine treatment related and dose limiting toxicities of this regimen in these patients. III. Determine the antileukemia activity of this regimen in these patients. IV. Correlate treatment related toxicities with steady state levels of topotecan in these patients.

OUTLINE: This is a dose escalation study of topotecan. Patients receive carboplatin IV continuously and fludarabine IV over 30 minutes on days 1-5, then topotecan IV continuously on days 6-8. Patients with residual leukemia in the bone marrow at day 15 may receive a second induction course. Patients who achieve partial or complete remission after 1-2 induction courses receive 1 consolidation course of fludarabine, carboplatin, and topotecan beginning 4-8 weeks after recovery from induction therapy. Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The first 3 patients do not receive any topotecan. The MTD is defined as the dose at which no more than 2 of 6 patients experience dose limiting toxicity. Patients are followed monthly for 6 months.

PROJECTED ACCRUAL: A total of 6-15 patients will be accrued for this study within 15-21 months.

  Eligibility
Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Criteria

DISEASE CHARACTERISTICS: Diagnosis of one of the following: Acute myelogenous leukemia (M0-M7) M3 must have received tretinoin as part of induction or salvage chemotherapy No greater than 2 prior intensive induction regimens Acute lymphocytic leukemia (L1 or L2) in first or second relapse Circulating blasts in blood or greater than 5% blasts in bone marrow No greater than 2 prior intensive induction regimens Chronic myelogenous leukemia in myeloid or lymphoid blast crisis Initial diagnosis OR No greater than 2 prior intensive induction regimens Acute myelogenous leukemia secondary to prior myelodysplastic syndrome or prior cytotoxic therapy No greater than 2 prior intensive induction regimens Myelodysplastic syndrome (must be neutropenic (absolute neutrophil count less than 500/mm3) or platelet or red cell transfusion dependent) Refractory anemia with excess blasts (RAEB) OR RAEB in transformation OR Chronic myelomonocytic leukemia Relapse after greater than 3 months since prior autologous stem cell transplant allowed No relapse after allogeneic bone marrow transplant No active CNS leukemia

PATIENT CHARACTERISTICS: Age: 12 and over Performance status: ECOG 0-3 Life expectancy: At least 4 weeks Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 2.0 mg/dL AST and ALT less than 3 times upper limit of normal Renal: Creatinine clearance at least 50 mL/min Cardiovascular: No symptomatic cardiac disease No active ischemic heart disease No poorly controlled congestive heart failure No myocardial infarction within past 6 months Cardiac ejection fraction at least 40% Pulmonary: No symptomatic pulmonary disease No symptomatic restrictive or obstructive lung disease Other: Not pregnant or nursing Fertile patients must use effective contraception No active infections, unless receiving antibiotics and clinically stable Fever caused by tumor allowed HIV negative No other active malignant disease Curatively treated prior malignancies allowed No severe neurologic disease

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics At least 5 days since prior hematopoietic growth factors Chemotherapy: See Disease Characteristics At least 24 hours since prior hydroxyurea At least 2 weeks since other prior cytotoxic anticancer therapy Prior carboplatin, fludarabine, or topotecan allowed Endocrine therapy: Concurrent corticosteroids allowed Radiotherapy: Not specified Surgery: Not specified

  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005593

Locations
United States, Ohio
Ireland Cancer Center    
      Cleveland, Ohio, United States, 44106-5065

Sponsors and Collaborators
Ireland Cancer Center
National Cancer Institute (NCI)

Investigators
Study Chair:     Brenda W. Cooper, MD     Case Comprehensive Cancer Center    
  More Information


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

Publications of Results:
Cooper BW, Ksenich P, Koc O, et al.: A phase I and pharmacodynamic study of fludarabine, carboplatin, and topotecan (FCT) for relapsed/refractory acute leukemia (RAL) and advanced myelodysplastic syndromes (MDS). [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1207, 2001.
 

Study ID Numbers:   CDR0000067699, CWRU-1998, CWRU-059812, NCI-G00-1732
First Received:   May 2, 2000
Last Updated:   July 23, 2008
ClinicalTrials.gov Identifier:   NCT00005593
Health Authority:   United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent childhood acute lymphoblastic leukemia  
recurrent childhood acute myeloid leukemia  
recurrent adult acute myeloid leukemia  
recurrent adult acute lymphoblastic leukemia  
relapsing chronic myelogenous leukemia  
blastic phase chronic myelogenous leukemia  
L1 childhood acute lymphoblastic leukemia  
L2 childhood acute lymphoblastic leukemia  
L1 adult acute lymphoblastic leukemia  
L2 adult acute lymphoblastic leukemia  
adult acute erythroid leukemia (M6)  
adult acute myeloblastic leukemia without maturation (M1)  
adult acute myeloblastic leukemia with maturation (M2)  
adult acute promyelocytic leukemia (M3)  
adult acute myelomonocytic leukemia (M4)  
adult acute monoblastic leukemia (M5a)
adult acute megakaryoblastic leukemia (M7)
childhood acute myeloblastic leukemia without maturation (M1)
childhood acute myeloblastic leukemia with maturation (M2)
childhood acute promyelocytic leukemia (M3)
childhood acute myelomonocytic leukemia (M4)
childhood acute monoblastic leukemia (M5a)
childhood acute monocytic leukemia (M5b)
childhood acute erythroleukemia (M6)
childhood acute megakaryocytic leukemia (M7)
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
secondary acute myeloid leukemia
adult acute monocytic leukemia (M5b)

Study placed in the following topic categories:
Leukemia, Monocytic, Acute
Blast Crisis
Leukemia, Lymphoid
Precancerous Conditions
Chronic myelogenous leukemia
Chronic myelomonocytic leukemia
Refractory anemia
Acute myelomonocytic leukemia
Di Guglielmo's syndrome
Leukemia, Myeloid, Acute
Acute lymphoblastic leukemia, adult
Leukemia
Preleukemia
Anemia, Refractory
Leukemia, Promyelocytic, Acute
Neoplasm Metastasis
Acute erythroblastic leukemia
Acute myeloid leukemia, adult
Acute myelocytic leukemia
Myelodysplastic syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Myelodysplasia
Acute promyelocytic leukemia
Acute myelogenous leukemia
Anemia
Carboplatin
Fludarabine monophosphate

Additional relevant MeSH terms:
Antimetabolites
Neoplasms by Histologic Type
Disease
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Pathologic Processes
Therapeutic Uses
Syndrome

ClinicalTrials.gov processed this record on December 03, 2008




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