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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 16-59


Phase 1/Phase 2
16 Years
59 Years
Not Enrolling
Both
Leukemia

Thank you

Trial Information

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 16-59


OBJECTIVES:

- 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.

Inclusion 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

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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum Tolerated Dose (MTD)

Outcome Description:

Determine the maximum tolerated dose (MTD) of topotecan when combined with daunorubicin, cytarabine, and etoposide in patients with de novo acute myeloid leukemia. 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.

Outcome Time Frame:

2 years

Safety Issue:

No

Principal Investigator

Hussain I. Saba, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute

Authority:

United States: Food and Drug Administration

Study ID:

MCC-11941

NCT ID:

NCT00005793

Start Date:

July 1999

Completion Date:

November 2006

Related Keywords:

  • Leukemia
  • untreated adult acute myeloid leukemia
  • adult acute erythroid leukemia (M6)
  • adult acute myeloblastic leukemia without maturation (M1)
  • adult acute myeloblastic leukemia with maturation (M2)
  • adult acute myelomonocytic leukemia (M4)
  • adult acute monoblastic leukemia (M5a)
  • adult acute megakaryoblastic leukemia (M7)
  • adult acute monocytic leukemia (M5b)
  • adult acute minimally differentiated myeloid leukemia (M0)
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • Leukemia

Name

Location

H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612