Tipifarnib, Cytarabine, and Daunorubicin in Treating Older Patients With Acute Myeloid Leukemia

NCT00101153 | Completed Phase 1

• 3 other identifiers: PMH-PHL-026CDR0000405840NCI-6670
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and daunorubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving tipifarnib together with cytarabine and daunorubicin may kill more cancer cells. PURPOSE: This phase I trial is studying the side effects and best dose of tipifarnib when given with cytarabine and daunorubicin in treating older patients with acute myeloid leukemia.

Conditions

Leukemia

Keywords

adult acute basophilic leukemia; adult acute eosinophilic leukemia; adult acute megakaryoblastic leukemia (M7); adult acute minimally differentiated myeloid leukemia (M0); adult acute monoblastic leukemia (M5a); adult acute monocytic leukemia (M5b); adult acute myeloblastic leukemia with maturation (M2); adult acute myeloblastic leukemia without maturation (M1); 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); adult acute myelomonocytic leukemia (M4); adult erythroleukemia (M6a); adult pure erythroid leukemia (M6b); untreated adult acute myeloid leukemia

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose of tipifarnib when administered with cytarabine and daunorubicin

  minimum of 30 days per treatment cycle

• Toxicity

  All cycles

• Pharmacokinetics

  Day 6

Study Arms (1)

Tipifarnib with conventional induction and consolidation

EXPERIMENTAL

Drug: cytarabine; Drug: daunorubicin hydrochloride; Drug: tipifarnib

Interventions

cytarabine DRUG

Tipifarnib with conventional induction and consolidation

daunorubicin hydrochloride DRUG

Tipifarnib with conventional induction and consolidation

tipifarnib DRUG

Tipifarnib with conventional induction and consolidation

Eligibility Criteria

• Age: 56 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Diagnosis of acute myeloid leukemia (AML) * All subtypes, except acute promyelocytic leukemia, are allowed * At least 20% bone marrow or peripheral blood blasts OR biopsy-confirmed extramedullary disease * No cerebrospinal fluid involvement PATIENT CHARACTERISTICS: Age * 56 and over Performance status * ECOG 0-2 OR * Karnofsky 60-100% Life expectancy * Not specified Hematopoietic * See Disease Characteristics * WBC \< 100,000/mm\^3 (treatment with hydroxyurea allowed) Hepatic * Bilirubin ≤ 1.25 times upper limit of normal (ULN) * AST and ALT ≤ 2.0 times ULN Renal * Creatinine \< 1.7 mg/dL OR * Creatinine clearance ≥ 60 mL/min Cardiovascular * LVEF ≥ 50% * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia Immunologic * HIV negative * No history of allergic reaction attributed to compounds of similar chemical or biologic composition to tipifarnib or imidazole drugs (e.g., ketoconazole, clotrimazole, or miconazole) * No ongoing or active infection Other * Not pregnant * Fertile patients must use effective contraception * Able to swallow oral medications * No other uncontrolled illness * No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior chemotherapy for AML except hydroxyurea for cytoreduction * More than 4 weeks since prior chemotherapy except hydroxyurea (6 weeks for nitrosoureas or mitomycin) and recovered * At least 24 hours since prior hydroxyurea Endocrine therapy * No concurrent dexamethasone Radiotherapy * More than 4 weeks since prior radiotherapy and recovered * No prior radiotherapy \> 3,000 cGy to marrow-producing areas Surgery * Not specified Other * No other concurrent investigational agents * No other concurrent antileukemic agents * No concurrent treatment with any of the following: * Ketoconazole * Itraconazole * Voriconazole * Clarithromycin * Erythromycin * Phenytoin * Carbamazepine * Barbiturates * Cyclosporine * Pimozide * Warfarin * Grapefruit juice * Simvastatin * Lovastatin * Atorvastatin * No concurrent magnesium- or aluminum-containing antacids within 2 hours before or after tipifarnib administration

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

Sponsors & Collaborators

• University Health Network, Toronto: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

London Regional Cancer Program at London Health Sciences Centre

London, Ontario, N6A 465, Canada

Location

Related Publications (1)

• Brandwein JM, Leber BF, Howson-Jan K, Schimmer AD, Schuh AC, Gupta V, Yee KW, Wright J, Moore M, MacAlpine K, Minden MD; NCI CTEP Protocol 6670. A phase I study of tipifarnib combined with conventional induction and consolidation therapy for previously untreated patients with acute myeloid leukemia aged 60 years and over. Leukemia. 2009 Apr;23(4):631-4. doi: 10.1038/leu.2008.341. Epub 2008 Dec 18.

  PMID: 19092853 RESULT

MeSH Terms

Conditions

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

Interventions

Cytarabine; Daunorubicin; tipifarnib

Condition Hierarchy (Ancestors)

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

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

Study Officials

• Joseph Brandwein, MD

  Princess Margaret Hospital, Canada

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2005
• First Posted: January 10, 2005
• Study Start: April 1, 2007
• Primary Completion: March 1, 2010
• Last Updated: July 23, 2015

Record last verified: 2015-07

Locations

CA (2)