An Open Label Phase II Study of Tipifarnib in Subjects With Relapsed or Refractory Peripheral T-Cell Lymphoma
Overview
- Phase
- Phase 2
- Intervention
- Tipifarnib
- Conditions
- Relapsed or Refractory Peripheral T-Cell Lymphoma
- Sponsor
- Kura Oncology, Inc.
- Enrollment
- 65
- Locations
- 13
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
Phase II study designed to investigate antitumor activity in terms of objective response rate (ORR) of tipifarnib subjects with advanced Peripheral T-Cell Lymphoma (PTCL). Tipifarnib will be administered orally until disease progression.
Detailed Description
This Phase II study will investigate the antitumor activity in terms of ORR of tipifarnib in subjects with relapsed or refractory PTCL. The first 18 subjects may be of the following PTCL sub-types: PTCL not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), ALK-positive and negative anaplastic large cell lymphoma (ALCL), hepatosplenic T-cell lymphoma, enteropathy-associate T-cell lymphoma (EATL), extranodal natural killer (NK) T-cell lymphoma, nasal type and subcutaneous panniculitis-like T-cell lymphoma. The AITL expansion cohort (N=32) will enroll only subjects with AITL. An additional cohort of patients (N=12) expressing the wild type CXCL12 3' UTR will be enrolled in order to explore the benefits of tipifarnib treatment observed in patients having an absence of this gene variation or single nucleotide variation (SNV). Tumor response assessments will be conducted according to Lugano Classification and/or mSWAT criteria. Tumor assessments will be performed approximately every 8 weeks (cycles 2-6) and at least once approximately every 12 weeks thereafter (Cycles 9, 12, 15, etc.), and will continue until disease progression. Subjects experiencing a complete response may be considered for bone marrow transplantation. Upon disease progression, all subjects will be followed for survival and the use of subsequent therapy. All subjects will be followed for safety during treatment and up to approximately 30 days after treatment discontinuation or until before the initiation of another anti-cancer therapy. Additional follow up may be implemented until the subject recovers from any emergent treatment related toxicity or the adverse event is considered irreversible by the investigator.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of PTCL according to the most recent edition of the World Health Organization (WHO) Classification of Tumors of Hematopoietic or Lymphoid Tissues, as follows:
- •Anaplastic large cell lymphoma (ALCL), ALK positive
- •ALCL, ALK negative
- •Angioimmunoblastic T-cell lymphoma (AITL)
- •Enteropathy-associated T-cell lymphoma
- •Extranodal natural killer (NK) T-cell lymphoma, nasal type
- •Hepatosplenic T-cell lymphoma
- •Peripheral T-cell lymphoma, not otherwise specified (NOS)
- •Subcutaneous panniculitis-like T-cell lymphoma
- •For enrollment into the AITL expansion cohort, subjects must have the diagnosis of AITL, nodal PTCL with T-follicular helper phenotype or follicular PTC.
Exclusion Criteria
- •Diagnosis of any of the following:
- •Precursor T-cell lymphoma or leukemia
- •Adult T-cell lymphoma/leukemia (ATLL)
- •T-cell prolymphocytic leukemia
- •T-cell large granular lymphocytic leukemia
- •Primary cutaneous type anaplastic large cell lymphoma
- •Mycosis fungoide/Sezary syndrome
- •Ongoing treatment with an anticancer agent not contemplated in this protocol.
- •Prior treatment (at least 1 full treatment cycle) with an FTase inhibitor.
- •Any history of clinically relevant coronary artery disease or myocardial infarction within the last 3 years.
Arms & Interventions
Tipifarnib
tipifarnib, oral
Intervention: Tipifarnib
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: Up to approximately 3 years
The ORR (complete response \[CR\] or partial response \[PRs\]) of tipifarnib was based on response assessments according to the Lugano Classification. Two-sided 95% confidence intervals (CIs) were based on either Wilson approximation (N \> 4) or Clopper-Pearson method (N ≤ 4). CR: PET-CT-based response, score of 1-3 on five-point scale (5PS) for lymph nodes and extralymphatic sites, no evidence of fluorodeoxyglucose (FDG)-avid disease in marrow. CT-based response, target nodes and masses regress to 1.5 cm in longest transverse diameter, no extralymphatic sites of disease, normal bone marrow morphology. PR: PET-CT-based response, score of 4-5 on 5PS with reduced uptake compared to baseline for lymph nodes and extralymphatic sites, residual uptake reduced compared to baseline in the bone marrow. CT-based response, ≥ 50% decrease in sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites, spleen regressed by \> 50% in length beyond normal.
Secondary Outcomes
- Number of Subjects That Experienced One or More Treatment-emergent Adverse Events (TEAEs)(Up to approximately 3 years)
- Progression-free Survival (PFS)(Up to approximately 3 years)
- Duration of Response (DOR)(Up to approximately 3 years)