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Phase I Trial of Sequential Topotecan(NSC 609699)and Etoposide for Patients With Relapsed, Refractory,or High Risk Acute Myeloid or Lymphoid Leukemia


Phase 1
18 Years
N/A
Not Enrolling
Both
Leukemia

Thank you

Trial Information

Phase I Trial of Sequential Topotecan(NSC 609699)and Etoposide for Patients With Relapsed, Refractory,or High Risk Acute Myeloid or Lymphoid Leukemia


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.

Inclusion 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

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 combined with etoposide in patients with relapsed or refractory acute myelogenous leukemia, acute lymphoblastic leukemia, or blastic phase chronic myelogenous leukemia.

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:

CWRU2994

NCT ID:

NCT00002588

Start Date:

August 1994

Completion Date:

January 2001

Related Keywords:

  • Leukemia
  • 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)
  • Leukemia

Name

Location

Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065