Relapsed or Refractory Peripheral T-Cell LymphomaPhase 2PTCLNCT02464228
Investigation of Tipifarnib in Treatment of Subjects With Peripheral T-Cell Lymphoma (PTCL) That Have Not Responded to Standard Therapy
A Phase 2 study testing Tipifarnib in people with Relapsed or Refractory Peripheral T-Cell Lymphoma, run by Kura Oncology, Inc. at 13 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Peripheral T-Cell Lymphoma
- What is being tested?
- Tipifarnib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 13 sitesin 3 countries
- Study dates
- 25 Feb 2016to 31 Mar 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 24Show fewer
- 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.
- 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.
- ECOG performance status of 0-2
- Acceptable liver and renal function
- Acceptable hematologic status
- Female subjects must be either:
- Of non-child-bearing potential (surgically sterilized or at least 2 years post- menopausal); or
- 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.
- Not breast feeding at any time during the study.
- Written and voluntary informed consent.
Who cannot join
- 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
Show all 22Show fewer
- 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.
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
- Known infection with HIV, or an active infection with hepatitis B or hepatitis C.
- 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.
- 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.
- The subject has legal incapacity or limited legal capacity.
- Dementia or significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
- Unwillingness or inability to comply with the study protocol for any reason.
Trial locations and contacts
13 sites in 3 countries.
13 sites in 3 countries
Spain7 sites
Hospital Universitari Vall d'Hebron
Barcelona, 08035
Institut Catala d'Oncologia de Girona
Girona, 17007
MD Anderson Cancer Center Madrid
Madrid, 28033
Hospital Universitario 12 Octubre de Madrid
Madrid, 28041
Hospital Universitario de Salamanca
Salamanca, 37007
Hospital Universitario Virgen del Rocio
Seville, 41013
Hospital Clinico Universitario de Valencia
Valencia, 46010
United States5 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Yale University, Yale Cancer Center
New Haven, Connecticut, 06520
Stanford University Medical Center
Palo Alto, California, 94305
Mayo Clinic
Rochester, Minnesota, 55905
H. Lee Moffitt Cancer Center & Research Institute, Inc.
Tampa, Florida, 33612
About this study
Official title: An Open Label Phase II Study of Tipifarnib in Subjects With Relapsed or Refractory Peripheral T-Cell Lymphoma
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.
Read the 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.
- Being tested
- Tipifarnib
- 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
- Medical subject headings
- Recurrence, Lymphoma, T-Cell, Peripheral, Lymphoma, Lymphoma, Extranodal NK-T-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TipifarnibDrug
Also called Zarnesta
oral
| Study group | Role | What they receive |
|---|---|---|
| Tipifarnib | Experimental | tipifarnib, oral Receives: Drug: Tipifarnib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to approximately 3 years
Secondary outcomes (3)
Progression-free Survival (PFS)
PFS was defined as the time (in months) from first dose (Cycle 1 Day 1) to either first observation of progressive disease (PD) or occurrence of death due to any cause within 126 days (approximately 2 time-intervals for tumor assessments) of either first administration of tipifarnib or the last tumor assessment. Observation of PD could have been by either documented radiographic progression (i.e., scan results) or documentation of symptomatic or clinical progression agreed upon and documented by investigators. In subjects without a progression date or with a death date more than 126 days after the first administration of study drugs or the last tumor assessment, the PFS time was censored on the date of last tumor assessment or date of first administration of study tipifarnib. The duration of the PFS was analyzed using the Kaplan-Meier (KM) method. 95% CIs were calculated using Hall-Wellner Method.
Measured: Up to approximately 3 years
Duration of Response (DOR)
DOR was defined as the time (in months) from the start date of the objective response to the first date of either documented PD or death. No data imputations were conducted for missing data. In the event of a maintained response, the DOR was censored at the last evaluable non-PD assessment. The DOR was analyzed using the KM method. 95% CIs were calculated using Hall-Wellner Method.
Measured: Up to approximately 3 years
Number of Subjects That Experienced One or More Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which did not necessarily have a causal relationship with this treatment. TEAEs were defined as AEs that started on or after the first dose of study drug and within 30 days of the last administration of study drug or immediately before the initiation of any other anticancer therapy. The Investigator was required to grade the severity/intensity of each AE according to NCI-CTCAE version 4.03. If a severity/intensity of Grade 4 (life-threatening) or 5 (death) was applied to an AE, then the Investigator also reported the event as a serious AE.
Measured: Up to approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2015 (estimated)
- Study start25 Feb 2016
- Primary completion31 Mar 2021
- Study completion31 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsed or Refractory Peripheral T-Cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kura Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02464228
- Sponsor's protocol ID
- KO-TIP-002
- Acronym
- PTCL
- Status last verified
- Apr 2024
- First submitted
- 3 Jun 2015
- Last updated
- 26 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 38991123
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Phase II Study of Tipifarnib in Subjects With Relapsed or Refractory Peripheral T-Cell Lymphoma
- ClinicalTrials.gov ID
- NCT02464228
- Acronym / sponsor ID
- PTCL / KO-TIP-002
- Keywords
- PTCL-NOS, Lymphoma, AITL, Nodal T-follicular helper phenotype, ALCL, Hepatosplenic T-cell lymphoma, EATL, Extranodal (NK) T-cell lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- Kura Oncology, Inc.Industry (pharma, biotech, devices)
- Study start
- 25 Feb 2016 (actual)
- Primary completion
- 31 Mar 2021 (actual)
- Study completion
- 31 Mar 2021 (actual)
- First posted
- 8 Jun 2015 (estimated)
- Results
- Posted 26 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tipifarnib | Experimental | Drug: Tipifarnibtipifarnib, oral |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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:
- 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.
Key exclusion criteria (22 listed)
- Diagnosis of any of the following:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TipifarnibAlso: Zarnestaoral | Drug | Tipifarnib |
Primary outcome
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.
3 secondary outcomes
Progression-free Survival (PFS)
Time frame: Up to approximately 3 years
Duration of Response (DOR)
Time frame: Up to approximately 3 years
Number of Subjects That Experienced One or More Treatment-emergent Adverse Events (TEAEs)
Time frame: Up to approximately 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38991123Witzig 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tipifarnib in people with Relapsed or Refractory Peripheral T-Cell Lymphoma, run by Kura Oncology, Inc. at 13 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Spain, United States, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jun 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Up to approximately 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02464228, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jun 2024.