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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00005593
First Posted: February 25, 2004
Last Update Posted: June 11, 2010
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Case Comprehensive Cancer Center
  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 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Fludarabine, Carboplatin, and Topotecan for Patients With Relapsed/Refractory Acute Leukemia and Advanced Myelodysplastic Syndromes

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Determine the maximum tolerated dose of topotecan when administered with carboplatin and fludarabine. [ Time Frame: Patients are followed monthly for 6 months. ]

Enrollment: 31
Study Start Date: September 1998
Study Completion Date: March 2003
Primary Completion Date: April 2002 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: carboplatin
    Patients receive carboplatin IV continuously over 30 minutes on days 1-5. 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.
    Drug: fludarabine phosphate
    Patients receive fludarabine IV over 30 minutes on days 1-5. 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.
    Drug: topotecan hydrochloride
    This is a dose escalation study of topotecan. Patients receive 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.
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

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00005593


Locations
United States, Ohio
Ireland Cancer Center at University Hospitals Case Medical Center
Cleveland, Ohio, United States, 44106-5065
Sponsors and Collaborators
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
Study Chair: Brenda W. Cooper, MD Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
  More Information

Publications:
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.

Responsible Party: Brenda W. Cooper, MD, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00005593     History of Changes
Other Study ID Numbers: CWRU1998
P30CA043703 ( U.S. NIH Grant/Contract )
CWRU-1998
CWRU-059812
NCI-G00-1732
First Submitted: May 2, 2000
First Posted: February 25, 2004
Last Update Posted: June 11, 2010
Last Verified: June 2010

Keywords provided by Case Comprehensive Cancer Center:
adult acute erythroid leukemia (M6)
childhood acute erythroleukemia (M6)
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 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 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)

Additional relevant MeSH terms:
Syndrome
Leukemia
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Fludarabine
Fludarabine phosphate
Carboplatin
Topotecan
Vidarabine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors