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

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ClinicalTrials.gov Identifier: NCT02464228
Recruitment Status : Recruiting
First Posted : June 8, 2015
Last Update Posted : March 4, 2020
Sponsor:
Information provided by (Responsible Party):
Kura Oncology, Inc.

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.

Condition or disease Intervention/treatment Phase
Relapsed or Refractory Peripheral T-Cell Lymphoma Drug: Tipifarnib Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Phase II Study of Tipifarnib in Subjects With Relapsed or Refractory Peripheral T-Cell Lymphoma
Actual Study Start Date : October 8, 2015
Estimated Primary Completion Date : November 29, 2020
Estimated Study Completion Date : December 27, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Tipifarnib
tipifarnib, oral
Drug: Tipifarnib
oral
Other Name: Zarnesta




Primary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: 2 years ]
    Response assessments according to Lugano Classification and/or mSWAT


Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 2 years ]
    To determine the antitumor activity in terms of PFS in subjects with relapsed/refractory PTCL

  2. Duration of Response [ Time Frame: 1 year ]
    To determine the antitumor activity in terms of DOR in subjects with relapsed/refractory PTCL

  3. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02464228


Contacts
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Contact: Michael Kurman, MD 201-236-9730 medicalaffairs@kuraoncology.com

Locations
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United States, California
Stanford University Medical Center Recruiting
Palo Alto, California, United States, 94305
United States, Connecticut
Yale University, Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06520
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute, Inc. Recruiting
Tampa, Florida, United States, 33612
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Korea, Republic of
Samsung Medical Center Recruiting
Seoul, Korea, Republic of, 06351
Spain
Hospital Universitari Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Institut Catala d'Oncologia de Girona Recruiting
Girona, Spain, 17007
MD Anderson Cancer Center Madrid Recruiting
Madrid, Spain, 28033
Hospital Universitario 12 Octubre de Madrid Recruiting
Madrid, Spain, 28041
Hospital Universitario de Salamanca Recruiting
Salamanca, Spain, 37007
Hospital Universitario Virgen del Rocio Recruiting
Sevilla, Spain, 41013
Hospital Clinico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Sponsors and Collaborators
Kura Oncology, Inc.
Investigators
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Principal Investigator: Bridget Martell, MD CMO
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Responsible Party: Kura Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02464228    
Other Study ID Numbers: KO-TIP-002
First Posted: June 8, 2015    Key Record Dates
Last Update Posted: March 4, 2020
Last Verified: March 2020
Keywords provided by Kura Oncology, Inc.:
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
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Tipifarnib
Antineoplastic Agents