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Investigation of Tipifarnib in Treatment of Subjects With PTCL That Have Not Responded to Standard Therapy. (PTCL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02464228
Recruitment Status : Active, not recruiting
First Posted : June 8, 2015
Last Update Posted : June 23, 2020
Sponsor:
Information provided by (Responsible Party):
Kura Oncology, Inc.

Tracking Information
First Submitted Date  ICMJE June 3, 2015
First Posted Date  ICMJE June 8, 2015
Last Update Posted Date June 23, 2020
Actual Study Start Date  ICMJE October 8, 2015
Estimated Primary Completion Date January 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 2, 2020)
Objective response rate (ORR) [ Time Frame: 2 years ]
Response assessments according to Lugano Classification and/or mSWAT
Original Primary Outcome Measures  ICMJE
 (submitted: June 4, 2015)
Objective response rate (ORR) [ Time Frame: 2 years ]
Response assessments according to IWC and/or mSWAT
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 2, 2020)
  • Progression Free Survival [ Time Frame: 2 years ]
    To determine the antitumor activity in terms of PFS in subjects with relapsed/refractory PTCL
  • Duration of Response [ Time Frame: 1 year ]
    To determine the antitumor activity in terms of DOR in subjects with relapsed/refractory PTCL
  • Number of patients that experience Adverse Events (AEs) [ Time Frame: Until 30 days following end of study ]
    To evaluate the safety and tolerability of tipifarnib in subjects with relapsed/refractory PTCL
Original Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2015)
  • Progression Free Survival [ Time Frame: 2 years ]
  • Duration of Response [ Time Frame: 1 year ]
  • Number of patients that experience Adverse Events (AEs) [ Time Frame: Until 30 days following end of study ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Investigation of Tipifarnib in Treatment of Subjects With PTCL That Have Not Responded to Standard Therapy.
Official Title  ICMJE An Open Label Phase II Study of Tipifarnib in Subjects With Relapsed or Refractory Peripheral T-Cell Lymphoma
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapsed or Refractory Peripheral T-Cell Lymphoma
Intervention  ICMJE Drug: Tipifarnib
oral
Other Name: Zarnesta
Study Arms  ICMJE Experimental: Tipifarnib
tipifarnib, oral
Intervention: Drug: Tipifarnib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 19, 2020)
65
Original Estimated Enrollment  ICMJE
 (submitted: June 4, 2015)
30
Estimated Study Completion Date  ICMJE January 15, 2021
Estimated Primary Completion Date January 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 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:

    1. Anaplastic large cell lymphoma (ALCL), ALK positive
    2. ALCL, ALK negative
    3. Angioimmunoblastic T-cell lymphoma (AITL)
    4. Enteropathy-associated T-cell lymphoma
    5. Extranodal natural killer (NK) T-cell lymphoma, nasal type
    6. Hepatosplenic T-cell lymphoma
    7. Peripheral T-cell lymphoma, not otherwise specified (NOS)
    8. Subcutaneous panniculitis-like T-cell lymphoma
  2. For enrollment into the AITL expansion cohort, subjects must have the diagnosis of AITL, nodal PTCL with T-follicular helper phenotype or follicular PTC.
  3. 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.
  4. Relapsed or are refractory to at least 1 prior systemic cytotoxic therapy. -Subjects must have received conventional therapy as a prior therapy.
  5. Subject has consented to provide at least 6 unstained tumor slides (10 preferred) or an FFPE block for biomarker testing.
  6. Subject has measurable disease as determined by the Lugano Classification and/or mSWAT.
  7. At least 2 weeks since the last systemic therapy regimen prior to enrollment.
  8. At least 2 weeks since last radiotherapy if radiation was localized to the only site of measurable disease, unless there is documentation of disease progression of the irradiated site. Subjects must have recovered from all acute toxicities from radiotherapy.
  9. ECOG performance status of 0-2
  10. Acceptable liver and renal function
  11. Acceptable hematologic status
  12. Female subjects must be either:

    1. Of non-child-bearing potential (surgically sterilized or at least 2 years post- menopausal); or
    2. If of child-bearing potential, subject must use an adequate method of contraception consisting of two-barrier method or one barrier method with a spermicide or intrauterine device. Both females and male subjects with female partners of child- bearing potential must agree to use an adequate method of contraception for 2 weeks prior to screening, during, and at least 4 weeks after last dose of trial medication. Female subjects must have a negative serum or urine pregnancy test within 72 hours prior to start of trial medication.
    3. Not breast feeding at any time during the study.
  13. Written and voluntary informed consent.

Exclusion Criteria:

  1. Diagnosis of any of the following:

    1. Precursor T-cell lymphoma or leukemia
    2. Adult T-cell lymphoma/leukemia (ATLL)
    3. T-cell prolymphocytic leukemia
    4. T-cell large granular lymphocytic leukemia
    5. Primary cutaneous type anaplastic large cell lymphoma
    6. Mycosis fungoide/Sezary syndrome
  2. Ongoing treatment with an anticancer agent not contemplated in this protocol.
  3. Prior treatment (at least 1 full treatment cycle) with an FTase inhibitor.
  4. Any history of clinically relevant coronary artery disease or myocardial infarction within the last 3 years.
  5. Known central nervous system lymphoma.
  6. Stem cell transplant less than 3 months prior to enrolment.
  7. Non-tolerable > Grade 2 neuropathy or evidence of unstable neurological symptoms within 4 weeks of Cycle 1 Day 1.
  8. Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery.
  9. Other active malignancy requiring therapy such as radiation, chemotherapy, or immunotherapy.
  10. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.

    Known infection with HIV, or an active infection with hepatitis B or hepatitis C.

  11. Subjects who have exhibited allergic reactions to tipifarnib, or structural compounds similar to tipifarnib or to its excipients. This includes hypersensitivity to imidazoles, such as clotrimazole, ketoconazole, miconazole and others in this drug class.
  12. Concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.
  13. The subject has legal incapacity or limited legal capacity.
  14. Dementia or significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
  15. Unwillingness or inability to comply with the study protocol for any reason.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02464228
Other Study ID Numbers  ICMJE KO-TIP-002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kura Oncology, Inc.
Study Sponsor  ICMJE Kura Oncology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Bridget Martell, MD CMO
PRS Account Kura Oncology, Inc.
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP