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Phase I Study of Fludarabine, Carboplatin, and Topotecan for Patients With Relapsed/Refractory Acute Leukemia and Advanced Myelodysplastic Syndromes


Phase 1
12 Years
N/A
Not Enrolling
Both
Leukemia, Myelodysplastic Syndromes

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Trial Information

Phase I Study of Fludarabine, Carboplatin, and Topotecan for Patients With Relapsed/Refractory Acute Leukemia and Advanced Myelodysplastic Syndromes


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

Patients are followed monthly for 6 months.

Safety Issue:

Yes

Principal Investigator

Brenda W. Cooper, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Authority:

United States: Federal Government

Study ID:

CWRU1998

NCT ID:

NCT00005593

Start Date:

September 1998

Completion Date:

March 2003

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • 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
  • Leukemia
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location
Ireland Cancer Center at University Hospitals Case Medical Center Cleveland, Ohio  44106-5065