A Phase I/II Study of Induction Chemotherapy With Daunorubicin, Cytarabine, Topotecan and Etoposide

NCT00005793 | Completed Phase 1

• 2 other identifiers: MCC-11941CA 82533
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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/II trial to study the effectiveness of combination chemotherapy in treating patients who have previously untreated acute myeloid leukemia.

Conditions

Leukemia

Keywords

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)

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  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.

  2 years

Study Arms (1)

Combination Chemotherapy

EXPERIMENTAL

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.

Drug: Cytarabine; Drug: Daunorubicin; Drug: Etoposide; Drug: Topotecan

Interventions

Cytarabine DRUG

Combination Chemotherapy

Daunorubicin DRUG

Also known as: daunorubicin hydrochloride

Combination Chemotherapy

Etoposide DRUG

Combination Chemotherapy

Topotecan DRUG

Also known as: topotecan hydrochloride

Combination Chemotherapy

Eligibility Criteria

• Age: 16 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• National Cancer Institute (NCI): collaborator
• SmithKline Beecham: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612-9497, United States

Location

MeSH Terms

Conditions

Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Monocytic, Acute; Leukemia, Megakaryoblastic, Acute; Congenital Abnormalities

Interventions

Cytarabine; Daunorubicin; Etoposide; Topotecan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Camptothecin; Alkaloids

Study Officials

• Hussain I. Saba, MD, PhD

  H. Lee Moffitt Cancer Center and Research Institute

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2000
• First Posted: May 7, 2003
• Study Start: July 1, 1999
• Primary Completion: July 1, 2006
• Study Completion: November 1, 2006
• Last Updated: September 25, 2012

Record last verified: 2012-09

Locations

US (1)