Clinical trial NCT00002588: Combination Chemotherapy in Treating Patients With Recurrent or Refractory Leukemia
Official title: Phase I Trial of Sequential Topotecan(NSC 609699)and Etoposide for Patients With Relapsed, Refractory,or High Risk Acute Myeloid or Lymphoid Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Keywords: recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
blastic phase chronic myelogenous 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)
secondary acute myeloid leukemia
adult acute monocytic leukemia (M5b)
adult acute minimally differentiated myeloid leukemia (M0)
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-07-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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. Combining more than one drug may kill more cancer cells.

PURPOSE: Phase I trial to study the effectiveness of topotecan and etoposide in treating patients who have recurrent or refractory leukemia.

Detailed description: OBJECTIVES: I. Determine the maximum tolerated dose of topotecan when combined with etoposide in patients with relapsed or refractory acute myelogenous leukemia, acute lymphoblastic leukemia, or blastic phase chronic myelogenous leukemia. II. Determine the toxicity of this regimen in these patients. III. Measure serum levels of topotecan at steady state and correlate them with any change in topoisomerase II content in leukemic blasts. IV. Assess whether it is feasible to correlate any upregulation of topoisomerase II expression with tumor response to etoposide in subsequent Phase II studies. V. Assess whether levels of pretreatment expression of topoisomerases I and II in leukemic cells are predictive of clinical response. VI. Assess whether it is feasible to develop a pharmacodynamic assay based on posttreatment apoptotic changes in leukemic blasts and whether this could be correlated with tumor response in subsequent phase II trials. VII. Determine the response in patients treated with this regimen.

OUTLINE: Induction: 2-Drug Combination Chemotherapy. Topotecan, TOPO, NSC-609699; Etoposide, VP-16, NSC-141540. Consolidation: 2-Drug Combination Chemotherapy. TOPO; VP-16.

PROJECTED ACCRUAL: 15-23 patients will be accrued in approximately 18 months.

Eligibility criteria: DISEASE CHARACTERISTICS: Acute myelogenous leukemia (M0-M7) and acute lymphoblastic leukemia (L1-L2) Refractory or in first or subsequent relapse Circulating blasts present OR Greater than 5% blasts in bone marrow Acute myelogenous leukemia secondary to myelodysplastic syndrome or cytotoxic therapy Untreated OR Maximum of 2 intensive induction regimens Chronic myelogenous leukemia in blastic or lymphoid crisis Untreated OR Maximum of 2 intensive induction regimens No CNS leukemia

PATIENT CHARACTERISTICS: Age: Over 18 Performance status: ECOG 0-3 Life expectancy: At least 4 weeks Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL AST and ALT less than 3 times normal Alkaline phosphatase less than 3 times normal Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min Cardiovascular: No myocardial infarction within 6 months No active ischemic cardiac disease No poorly controlled congestive heart failure No other symptomatic cardiac disease Left ventricular ejection fraction at least 40% Pulmonary: No symptomatic restrictive or obstructive lung disease Other: No severe neurologic disease No active infection unless stable on antimicrobial therapy or fever is tumor related HIV negative Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: At least 2 weeks since prior cytotoxic therapy (except hydroxyurea and steroids) Biologic therapy: No prior bone marrow transplantation At least 3 days since prior hematopoietic growth factors Chemotherapy: No prior topotecan or camptothecin analogues Prior etoposide allowed Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Primary outcomes:
measure: Determine the maximum tolerated dose of topotecan when combined with etoposide in patients with relapsed or refractory acute myelogenous leukemia, acute lymphoblastic leukemia, or blastic phase chronic myelogenous leukemia.
Secondary outcomes:
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
name: Brenda W. Cooper, MD
role: STUDY_CHAIR
References:
citation: Cooper BW, Lazarus HM, Creger R, et al.: A phase I and pharmacodynamic study of sequential topotecan and etoposide (TE) in adult patients with refractory/relapsed acute leukemia (RAL) (Meeting abstact.). [Abstract] Proceedings of the American Society of Clinical Oncology 15: A1549, 1996.