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.
- Anaplastic Large Cell Lymphoma
- Brief Title: Study of Tipifarnib in Subjects With Relapsed or Refractory Peripheral T-Cell Lymphoma
- Official Title: An Open Label Phase II Study of Tipifarnib in Subjects With Relapsed or Refractory Peripheral T-Cell Lymphoma
Clinical Trial IDs
- ORG STUDY ID:
- NCT ID:
- Relapsed Peripheral T-Cell Lymphoma
- Refractory Peripheral T-Cell Lymphoma
This Phase II studyis designed to investigate the antitumor activity in terms of objective
response rate (ORR) of tipifarnib in 18 subjects with advanced Peripheral T-Cell Lymphoma
(PTCL). The total number of patients could be extended to 30 pending on the degree of
response observed at an interim analysis. Tipifarnib will be administered until disease
progression then followed approximately every 12 weeks for survival until either death or 12
months after accrual of the last study subject, whichever occurs first.
This Phase II study will investigate the antitumor activity in terms of ORR of tipifarnib in
subjects with relapsed or refractory PTCL. Up to 30 subjects may be enrolled in the study.
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=12) will enroll only subjects
A two-stage study design will be used for the first 18 subjects in order to minimize the
number of study subjects treated if tipifarnib were considered not sufficiently efficacious
to grant further development in this subject population. Tumor response assessments will be
conducted according to IWC and/or mSWAT criteria.
Tumor assessments will be performed approximately every 8 weeks on cycles 2-6 and at least
once approximately every 12 weeks thereafter (Cycles 9, 12, 15, etc.), and will continue
until disease progression. Subjects who have experienced a complete response may be
considered for transplantation. Upon disease progression, all subjects will be followed
approximately every 12 weeks for survival and the use of subsequent therapy until either
death or 12 months after accrual of the last study subject, whichever occurs first. All
subjects will be followed-up for safety during treatment and up to approximately 30 days (30
+/- 7 days) after treatment discontinuation or until immediately before the initiation of
another anti-cancer therapy, whichever occurs first. 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.
- Diagnosis of PTCL according to the most recent edition of the World Health
Organization (WHO) Classification of Tumors of Hematopoietic or Lymphoid Tissues, as
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, no otherwise specified (NOS)
8. Subcutaneous panniculitis-like T-cell lymphoma For enrollment into the AITL
expansion cohort, subjects must have he diagnosis of AITL.
- Relapsed or are refractory to at least 1 prior systemic cytotoxic therapy. -Subjects
must have received conventional therapy as a prior therapy.
- ECOG performance status of 0-2
- Acceptable liver and renal function
- Acceptable hematologic status
- Female subjects must be either:
1. Of non-child-bearing potential (surgically sterilized or at least 2 years
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.
- Written and voluntary informed consent.
- 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
- Ongoing treatment with an anticancer agent not contemplated in this protocol.
- 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
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy. Known infection with HIV, or an active infection with hepatitis B or
|Maximum Eligible Age:||N/A|
|Minimum Eligible Age:||18 Years|
Primary Outcome Measures
|Measure:||objective response rate (ORR)|
|Time Frame:||2 years|
|Description:||Response assessments according to IWC and/or mSWAT|
Secondary Outcome Measures
|Measure:||Progression Free Survival|
|Time Frame:||2 years|
|Measure:||Duration of Response|
|Time Frame:||1 year|
|Measure:||Number of patients that experience Adverse Events (AEs)|
|Time Frame:||Until 30 days following end of study|
|Lead Sponsor:||Kura Oncology, Inc.|