Phase 2 Trial of R115777 in Previously Untreated Older Adults With AML and Baseline Presence of a Specific 2-Gene Expression Signature Ratio
Overview
- Phase
- Phase 2
- Intervention
- Tipifarnib
- Conditions
- Adult Acute Megakaryoblastic Leukemia
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 21
- Locations
- 7
- Primary Endpoint
- Complete Remission (CR) Rate
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
This phase II trial is studying how well tipifarnib works in treating older patients with acute myeloid leukemia. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the complete remission (CR) rate in acute myeloid leukemia (AML) patients prospectively selected for tipifarnib (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates. SECONDARY OBJECTIVES: I. To determine the median overall and 1-year survival of patients treated with this regimen II. To determine the median relapse-free survival of patients treated with this regimen. III. To determine the safety of this regimen in these patients IV. To determine the immunophenotypic expression of RASGRP1 on baseline bone marrow blasts and assess correlation with PCR-based detection. OUTLINE: This is a multicenter study. Patients receive tipifarnib orally twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Bone marrow aspirate and/or biopsy are collected at baseline and on day 28 of course 1 and 2 for RasGRP1 protein expression analysis by qRT-PCR. After completion of study therapy, patients are followed up every 30 days.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Previously untreated acute myeloid leukemia (AML) (de novo or secondary)
- •No diagnosis of acute promyelocytic leukemia (APL)
- •Deemed unsuitable for or refuses standard induction chemotherapy
- •RASGRP1:APTX ratio \>= 5, through bone marrow screening
- •No patients with known leukemic involvement of the central nervous system
- •ECOG performance status =\< 2
- •No WBC \>= 30,000/uL (hydroxyurea permitted up to 24 hours prior to initiation of therapy)
- •Serum creatinine less than 1.5 times the upper limit of the normal range (ULN) (National Cancer Institute \[NCI\] Common Toxicity Criteria \[CTC\] Grade 1)
- •Total bilirubin less than 1.5 times ULN (unless the increase is unequivocally due to hemolysis or Gilbert syndrome)
- •ALT and AST less than 2.5 times ULN (NCI CTC Grade 1)
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (tipifarnib)
Patients receive tipifarnib orally twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Tipifarnib
Treatment (tipifarnib)
Patients receive tipifarnib orally twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Outcomes
Primary Outcomes
Complete Remission (CR) Rate
Time Frame: From first treatment through follow up period, an expected average of 12 months
Complete Remission (CR) rate in Acute Myelogenous Leukemia (AML) patients prospectively selected for R115777R115777 (ZARNESTRA) treatment on the basis of a 2-gene signature (RASGRP1:APTX ratio) in bone marrow aspirates. AML Complete Remission: Bone marrow aspiration - Less than 5% leukemic blasts, Auer rods not detected; Peripheral blood counts - Absolute neutrophil count \>/= 1,000/mm\^3, Platelet count \>/= 100,000/mm\^3, Leukemic blasts not present; Blood-product transfusion independence; Absence of extramedullary leukemia.
Secondary Outcomes
- Median Overall Survival (OS)(From first treatment through follow up period, an expected average of 12 months)
- Median 1-Year Survival Rate(1 year)
- Number of Participants With Relapse Free Survival(7 months)