An Adaptive Phase 2 Study of Tipifarnib in Subjects With Myelodysplastic Syndromes
Overview
- Phase
- Phase 2
- Intervention
- Tipifarnib
- Conditions
- Myelodysplastic Syndromes
- Sponsor
- Kura Oncology, Inc.
- Enrollment
- 16
- Locations
- 2
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Terminated
- Last Updated
- last year
Overview
Brief Summary
This is a Phase 2 randomized, open-label, two-stage study designed to investigate the antitumor activity of tipifarnib in approximately 36 eligible subjects with MDS who have no known curative treatment. Subjects will be randomized to receive tipifarnib orally with food according to one of 2 treatment regimens.
Detailed Description
This Phase 2 study will investigate the antitumor activity in terms of ORR of tipifarnib in approximately 36 eligible subjects with MDS who have no known curative treatment. Eligible subjects may have received no more than 2 prior systemic regimens. Subjects will be randomized to receive tipifarnib orally with food according to one of 2 dose regimens. In the absence of unmanageable toxicities, subjects may continue to receive tipifarnib treatment until disease progression. Disease assessments will be performed at screening and at least once every approximately 12 weeks starting at the end of cycle 3. Determination of ORR will be assessed by the Investigator according to the MDS International Working Group (IWG) criteria (Cheson 2006). Upon disease progression, all subjects in the study 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 study has been completed, whichever occurs first.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subject is at least 18 years of age.
- •Documented pathological evidence of MDS as defined by the World Health Organization (WHO) criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or
- •Subjects have no known curative treatment.
- •Subject is willing and able to comply with scheduled visits, treatment plans, laboratory tests and other procedures (including bone marrow assessments).
- •At least 1 week since the last systemic therapy regimen prior to Cycle 1 Day
- •Subjects must have recovered to NCI CTCAE v. 4.03 \< Grade 2 from all acute toxicities (excluding Grade 2 toxicities that are not considered a safety risk by the Sponsor and Investigator) or toxicity must be deemed irreversible by the Investigator.
- •Acceptable hematological function:
- •Absolute neutrophil count \< 1000/mm3
- •Platelet count \> 20,000/mm3
Exclusion Criteria
- •Known prior progression to acute myeloid leukemia (AML), defined by at least 20% blasts in the blood or bone marrow.
- •Myelodysplastic or myeloproliferative syndrome other than MDS.
- •More than two prior systemic regimens for MDS. Prior systemic regimens are those that are considered standard of care for the treatment of MDS, have been received at standard doses for at least one full treatment cycle and exclude ESA.
- •Prior cytoreductive therapy for blast reduction.
- •Participation in any interventional study within 1 week or 5 half lives (whichever is longer) of Cycle 1 Day
- •Ongoing treatment with an anticancer agent for MDS not contemplated in this protocol.
- •Prior treatment (at least 1 full treatment cycle) with a farnesyltransferase inhibitor.
- •Clinically significant anemia due to iron, B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding. If marrow stain for iron is not available, the transferrin saturation (iron/total iron binding capacity Fe/TIBC) must be \>20% or serum ferritin must be \>100 ng/dL.
- •Active coronary artery disease requiring treatment, myocardial infarction within the prior year, New York Heart Association grade III or greater congestive heart failure, cerebro-vascular attack within the prior year, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
- •Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery.
Arms & Interventions
Regimen 1: Tipifarnib
600 mg twice daily (bid) for 7 days on Days 1-7 in 28 day cycles.
Intervention: Tipifarnib
Regimen 2: Tipifarnib
300 mg bid for 21 days on Days 1-21 in 28 day cycles.
Intervention: Tipifarnib
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: 1 year
ORR was assessed by the investigator and included complete response (CR), partial response (PR), marrow complete remission (MR), and hematologic improvement (HI) according to the MDS International Working Group (IWG) criteria.
Secondary Outcomes
- Duration of Transfusion Independence(1 year)
- Rate of Transfusion Independence(1 year)
- Hematologic Improvement(1 year)
- Duration of Response(1 year)
- Progression-free Survival (PFS) at 1 Year(1 year)
- Overall Survival (OS) at 1 Year(1 year)
- Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)(1 year)