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

Primary Purpose

Leukemia, Myelodysplastic Syndromes

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
carboplatin
fludarabine phosphate
topotecan hydrochloride
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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), previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, adult acute minimally differentiated myeloid leukemia (M0), childhood acute minimally differentiated myeloid leukemia (M0), childhood myelodysplastic syndromes

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Ireland Cancer Center at University Hospitals Case Medical Center

Outcomes

Primary Outcome Measures

Determine the maximum tolerated dose of topotecan when administered with carboplatin and fludarabine.

Secondary Outcome Measures

Full Information

First Posted
May 2, 2000
Last Updated
June 9, 2010
Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00005593
Brief Title
Fludarabine, Carboplatin, and Topotecan in Treating Patients With Relapsed/Refractory Acute Leukemia or Advanced Myelodysplastic Syndrome
Official Title
Phase I Study of Fludarabine, Carboplatin, and Topotecan for Patients With Relapsed/Refractory Acute Leukemia and Advanced Myelodysplastic Syndromes
Study Type
Interventional

2. Study Status

Record Verification Date
June 2010
Overall Recruitment Status
Completed
Study Start Date
September 1998 (undefined)
Primary Completion Date
April 2002 (Actual)
Study Completion Date
March 2003 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myelodysplastic Syndromes
Keywords
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), previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, adult acute minimally differentiated myeloid leukemia (M0), childhood acute minimally differentiated myeloid leukemia (M0), childhood myelodysplastic syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
topotecan hydrochloride
Intervention Description
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.
Primary Outcome Measure Information:
Title
Determine the maximum tolerated dose of topotecan when administered with carboplatin and fludarabine.
Time Frame
Patients are followed monthly for 6 months.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brenda W. Cooper, MD
Organizational Affiliation
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Ireland Cancer Center at University Hospitals Case Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-5065
Country
United States

12. IPD Sharing Statement

Citations:
Citation
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.
Results Reference
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Fludarabine, Carboplatin, and Topotecan in Treating Patients With Relapsed/Refractory Acute Leukemia or Advanced Myelodysplastic Syndrome

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