Investigation of Tipifarnib in Treatment of Subjects With Peripheral T-Cell Lymphoma (PTCL) That Have Not Responded to Standard Therapy

NCT02464228 | Completed Phase 2 Results

• 1 other identifier: KO-TIP-002
• Study Type: interventional
• Target: 65
• Locations: 3 countries
• Sites: 13

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.

Conditions

Relapsed or Refractory Peripheral T-Cell Lymphoma

Keywords

PTCL-NOS; Lymphoma; AITL; Nodal T-follicular helper phenotype; ALCL; Hepatosplenic T-cell lymphoma; EATL; Extranodal (NK) T-cell lymphoma; Wild Type CXCL12 3' UTR

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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.

  Up to approximately 3 years

Secondary Outcomes (3)

• Progression-free Survival (PFS)

  Up to approximately 3 years

• Duration of Response (DOR)

  Up to approximately 3 years

• Number of Subjects That Experienced One or More Treatment-emergent Adverse Events (TEAEs)

  Up to approximately 3 years

Study Arms (1)

Tipifarnib

EXPERIMENTAL

tipifarnib, oral

Drug: Tipifarnib

Interventions

Tipifarnib DRUG

oral

Also known as: Zarnesta

Tipifarnib

Eligibility Criteria

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

You may qualify if:

• 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.
• For enrollment into the CXCL12+ PTCL expansion cohort, subjects must have the diagnosis of PTCL (a - h subtypes listed above, except AITL), consent to provide buccal swabs for CXCL12 SNP testing, and be found to be CXCL12+ based on testing by a Sponsor approved methodology.
• Relapsed or are refractory to at least 1 prior systemic cytotoxic therapy. -Subjects must have received conventional therapy as a prior therapy.
• Subject has consented to provide at least 6 unstained tumor slides (10 preferred) or an FFPE block for biomarker testing.
• Subject has measurable disease as determined by the Lugano Classification and/or mSWAT.
• At least 2 weeks since the last systemic therapy regimen prior to enrollment.

You may not qualify if:

• 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.
• Known central nervous system lymphoma.
• Stem cell transplant less than 3 months prior to enrolment.
• Non-tolerable \> Grade 2 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
• Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery.
• Other active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy.

Sponsors & Collaborators

• Kura Oncology, Inc.: lead

Study Sites (13)

Stanford University Medical Center

Palo Alto, California, 94305, United States

Location

Yale University, Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

H. Lee Moffitt Cancer Center & Research Institute, Inc.

Tampa, Florida, 33612, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Institut Catala d'Oncologia de Girona

Girona, 17007, Spain

Location

MD Anderson Cancer Center Madrid

Madrid, 28033, Spain

Location

Hospital Universitario 12 Octubre de Madrid

Madrid, 28041, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Related Publications (1)

• Witzig T, Sokol L, Kim WS, de la Cruz Vicente F, Martin Garcia-Sancho A, Advani R, Roncero Vidal JM, de Ona Navarrete R, Marin-Niebla A, Rodriguez Izquierdo A, Terol MJ, Domingo-Domenech E, Saunders A, Bendris N, Mackey J, Leoni M, Foss F. Phase 2 trial of the farnesyltransferase inhibitor tipifarnib for relapsed/refractory peripheral T-cell lymphoma. Blood Adv. 2024 Sep 10;8(17):4581-4592. doi: 10.1182/bloodadvances.2024012806.

  PMID: 38991123 DERIVED

MeSH Terms

Conditions

Recurrence; Lymphoma, T-Cell, Peripheral; Lymphoma; Lymphoma, Extranodal NK-T-Cell

Interventions

tipifarnib

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Clinical Operations
• Organization: Kura Oncology, Inc.

KO-TIP-002@kuraoncology.com

+1 617-588-3755

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: June 3, 2015
• First Posted: June 8, 2015
• Study Start: February 25, 2016
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: June 26, 2024
• Results First Posted: June 26, 2024

Record last verified: 2024-04

Locations

US (5); ES (7); KR (1)