Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy in Treating Patients With Previously Untreated Acute Myeloid Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Closed	16 to 59	NCI	MCC-11941 MCC-IRB-5367, NCI-G00-1751, NCT00005793

Objectives

1. Determine the maximum tolerated dose (MTD) of topotecan when combined with daunorubicin, cytarabine, and etoposide in patients with de novo acute myeloid leukemia.
2. Determine the efficacy of this regimen at the MTD of topotecan by measuring the complete response rate in this patient population.
3. Determine the days of hospitalization and number of infections associated with this regimen in these patients.
4. Correlate serum levels of topotecan and etoposide with the expression of topoisomerase I and II in tumor cells and in peripheral blood mononuclear cells (PBMN), as well as with toxicity and response rate in these patients.
5. Correlate tumor cell and PBMN expression and activity of topoisomerase I and II with hematological toxicity and clinical response in these patients.
6. Correlate levels of activation of STAT signaling proteins with expression of bcl-2 family proteins and response to chemotherapy in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed newly diagnosed, previously untreated acute myeloid leukemia (AML)
  • All FAB types, M0-M7, excluding M3
  • No AML after myelodysplastic syndrome

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior topotecan or any other DNA topoisomerase I inhibitor (e.g., irinotecan, aminocamptothecin, or nitrocamptothecin) or etoposide for any prior malignancy

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Patient Characteristics:

Age:

• 16 to 59

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin less than 2 mg/dL
• SGOT/SGPT normal unless due to leukemic disease
• Alkaline phosphatase normal unless due to leukemic disease

Renal:

• Creatinine no greater than 2.0 mg/dL

  OR

• Creatinine clearance greater than 60 mL/min

Cardiovascular:

• Ejection fraction at least 50% by MUGA
• No myocardial infarction or serious ventricular arrhythmia within the past 6 months

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other prior malignancy within the past 5 years except resected skin cancer
• HIV negative

Expected Enrollment

A total of 3-36 patients (phase I) and then an additional 24-27 patients (phase II) will be accrued for this study within 4 years.

Outline

This is a dose-escalation study of topotecan (phase I) followed by a response rate-determination (phase II) study.

Patients receive induction chemotherapy with daunorubicin IV over 10-15 minutes on days 1-3, cytarabine IV continuously on days 1-5, topotecan IV continuously on days 6-8, and etoposide IV over 60 minutes on days 9 and 10. Within 4 weeks of hematologic recovery, patients achieving remission after induction receive consolidation chemotherapy with cytarabine IV over 1 hour every 12 hours on days 1, 3, and 5. Subsequent courses of consolidation chemotherapy begin within 2 weeks of documentation of hematologic recovery from the prior consolidation course. Consolidation chemotherapy continues for 4 courses in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of topotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive induction chemotherapy at the recommended phase II dose.

Patients are followed at 1 month, every 2 months for 1 year, every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

Hussain Saba, MD, PhD, Protocol chair		Ph: 813-745-4261; 888-663-3488 Email: saba@moffitt.usf.edu

Registry Information
Official Title		A Phase I/II Study of Induction Chemotherapy with Daunorubicin, Cytarabine, Topotecan and Etoposide (DATE) for De Novo AML: In the Treatment of Young Patients Ages 16-60
Trial Start Date		2000-07-05
Registered in ClinicalTrials.gov		NCT00005793
Date Submitted to PDQ		2000-03-07
Information Last Verified		2005-01-13
NCI Grant/Contract Number		P30-CA76292

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