Tipifarnib in Treating Patients With Anemia or Neutropenia and Large Granular Lymphocyte Leukemia

NCT00360776 | Terminated Phase 2

• 4 other identifiers: NCI-2009-000865402CDR0000489291U01CA062502
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial is studying how well tipifarnib works in treating patients with anemia or neutropenia and large granular lymphocyte leukemia. Tipifarnib may stop the growth of leukemia by blocking blood flow to the cancer cells and by blocking some of the enzymes needed for cancer cell growth.

Conditions

Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia; T-cell Large Granular Lymphocyte Leukemia

Outcome Measures

Primary Outcomes (1)

• Response rates to tipifarib defined as the proportion of patients achieving a complete response (CCR) or partial response (PR)

  Up to 5 years

Secondary Outcomes (1)

• Changes in Ras/ERK and NK receptor expression

  Baseline to 5 years

Study Arms (1)

Arm I

EXPERIMENTAL

Patients will receive tipifarnib by mouth twice a day for 3 weeks. Treatment may repeat every 4 weeks for up to eight courses. Patients will undergo blood collection periodically for laboratory studies. After finishing treatment, patients will be evaluated every 6 months for 5 years.

Drug: tipifarnib; Other: laboratory biomarker analysis

Interventions

tipifarnib DRUG

Given orally

Also known as: R115777, Zarnestra

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

Eligibility Criteria

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

You may qualify if:

• Diagnosis of T-cell-large granular lymphocyte (LGL) leukemia or natural killer (NK)-LGL leukemia associated with ≥ 1 of the following clinical manifestations:
• Severe neutropenia (i.e., \< 500/mm³)
• Neutropenia associated with recurrent infections, meeting 1 of the following criteria: one severe infection requiring hospitalization or at least 2 infections requiring antibiotic therapy
• Symptomatic anemia with significant fatigue with a score of greater than 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale; dyspnea on exertion, but able to walk one flight of stairs without stopping (less than grade 1 respiratory symptoms); cardiac symptoms including worsening of angina or new onset of chest pain
• Transfusion-dependent anemia
• Willing to discontinue use of MTX, Cy, or cyclosporine for 1 month prior to study entry
• T-cell-LGL leukemia must meet all of the following criteria: CD3+ and CD57+ cells \> 300/mm³ or CD8+ cells \> 650/mm³ by phenotypic studies of peripheral blood, evidence for clonal T-cell receptor gene rearrangement based on positive flow cytometric analysis, T-cell receptor (TCR)-γ chain polymerase chain reaction (PCR), TCR-Vβ PCR, or by Southern blot analysis
• NK-LGL leukemia must have CD56+ or CD16+ NK cells \> 750/mm³ by phenotypic studies of peripheral blood
• Life expectancy \> 2 years
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Fertile patients must use effective contraception prior to and during study
• Negative pregnancy test
• Normal kidney and liver function, as determined by the following laboratory results: total bilirubin less than or equal to 2.0 mg/dl; AST (SGOT) and ALT (SGPT) less than or equal to 2.5 times the upper limit of normal; and creatinine less than or equal to 2.0 mg/dl

You may not qualify if:

• Not pregnant or nursing
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to tipifarnib
• No allergies to imidazoles (e.g., clotrimazole, ketoconazole, miconazole, econazole, fenticonazole, isoconazole, sulconazole, tioconazole, or terconazole)
• No uncontrolled concurrent illness including, but not limited to, any of the following: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness or social situations that would limit study compliance
• No other serious medical illness that would limit survival to \< 2 years
• No other malignancy within the past 5 years except inactive nonmelanoma skin cancer or carcinoma in situ of the cervix
• Psychiatric illness that may interfere with study participation
• No other anticancer agents or therapies
• No concurrent antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No prior tipifarnib or other inhibitors of MAPK signaling intermediates

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Large Granular Lymphocytic

Interventions

tipifarnib

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, T-Cell

Study Officials

• Thomas Loughran

  Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2006
• First Posted: August 7, 2006
• Study Start: June 2, 2006
• Primary Completion: May 14, 2007
• Last Updated: April 5, 2017

Record last verified: 2017-04

Locations

US (1)