A Phase I/II Study of Induction Chemotherapy With Daunorubicin, Cytarabine, Topotecan and Etoposide
NCT ID: NCT00005793
Last Updated: 2012-09-25
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1/PHASE2
41 participants
INTERVENTIONAL
1999-07-31
2006-11-30
Brief Summary
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PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy in treating patients who have previously untreated acute myeloid leukemia.
Detailed Description
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* Determine the maximum tolerated dose (MTD) of topotecan when combined with daunorubicin, cytarabine, and etoposide in patients with de novo acute myeloid leukemia.
* Determine the efficacy of this regimen at the MTD of topotecan by measuring the complete response rate in this patient population.
* Determine the days of hospitalization and number of infections associated with this regimen in these patients.
* 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.
* Correlate tumor cell and PBMN expression and activity of topoisomerase I and II with hematological toxicity and clinical response in these patients.
* Correlate levels of activation of STAT signaling proteins with expression of bcl-2 family proteins and response to chemotherapy in these patients.
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.
PROJECTED ACCRUAL: 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.
Conditions
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Keywords
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Combination Chemotherapy
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.
Cytarabine
Daunorubicin
Etoposide
Topotecan
Interventions
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Cytarabine
Daunorubicin
Etoposide
Topotecan
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Histologically confirmed newly diagnosed, previously untreated acute myeloid leukemia (AML)
* All FAB types, M0-M7, excluding M3
* No AML after myelodysplastic syndrome
PATIENT CHARACTERISTICS:
Age:
* 16 to 59
Performance status:
* Eastern Cooperative Oncology Group (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
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
16 Years
59 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
SmithKline Beecham
INDUSTRY
H. Lee Moffitt Cancer Center and Research Institute
OTHER
Responsible Party
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Principal Investigators
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Hussain I. Saba, MD, PhD
Role: STUDY_CHAIR
H. Lee Moffitt Cancer Center and Research Institute
Locations
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H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States
Countries
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Other Identifiers
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CA 82533
Identifier Type: OTHER
Identifier Source: secondary_id
MCC-11941
Identifier Type: -
Identifier Source: org_study_id