Clinical Trial: Tipifarnib in Subjects With Chronic Myelomonocytic Leukemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 2 Study of Tipifarnib in Subjects With Chronic Myelomonocytic Leukemia

Brief Summary: A Phase 2 study to investigate the antitumor activity in terms of overall response rate (ORR) of tipifarnib in approximately 20 eligible subjects with CMML. Subjects will receive tipifarnib administered orally, twice a day (bid) for 7 days in alternating weeks (Days 1-7 and 15-21) in 28 day cycles. In the absence of unmanageable toxicities, subjects may continue to receive tipifarnib treatment until disease progression. If a complete response is observed, therapy with tipifarnib will be maintained for at least 6 months beyond the start of response.

Detailed Summary:

This Phase 2 study will investigate the antitumor activity in terms of ORR of tipifarnib in approximately 20 eligible subjects with CMML. This trial is planned as a single treatment trial with statistical comparison to historical ORR rate. The primary objective is to provide evidence that the TRUE underlying ORR in all subjects and/or in the KRAS/NRAS wild-type subgroup exceeds the historical rate. Only consented subjects who meet all eligibility criteria will be enrolled in the study. Eligible subjects will receive tipifarnib administered at a starting dose of 1200 mg or 900 mg, orally with food, bid for 7 days in alternating weeks (Days 1-7 and 15-21) in 28 day cycles. Stepwise 300 mg dose reductions to control treatment-related, treatment-emergent toxicities are allowed.

If a complete response is observed, therapy with tipifarnib will be maintained for at least 6 months beyond the start of response. In the absence of unmanageable toxicities, subjects may continue to receive tipifarnib treatment until disease progression. Provisions will be made for the continuation of study treatment in subjects whose disease has not progressed beyond the end of the study, e.g. a single patient treatment protocol.

Determination of disease response will be performed by the Investigator according to the MDS/MPN IWG criteria. Similarly, disease progression will also be determined based on the MDS/MPN IWG criteria. 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 study cohort has been completed, whichever occurs first. Information on survival and subsequent anticancer therapy may be collected by phone.


Sponsor: Kura Oncology, Inc.

Current Primary Outcome:

  • Number of patients with CMML who obtain objective response following treatment with tipfarnib [ Time Frame: 1 year ]
  • Number of patients with CMML whose disease is KRAS/NRAS wild type who obtain objective response following treatment with tipfarnib. [ Time Frame: 1 year ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Rate of complete response (CR) [ Time Frame: 1 year ]
  • Duration of Response [ Time Frame: 1 year ]
  • Rate of progression free survival (PFS) [ Time Frame: 1 year ]
  • Rate of survival [ Time Frame: 1 year ]
  • Number of patients that experience Adverse Events (AEs) [ Time Frame: Until 30 days following end of study ]
  • Rate of complete cytogenetic remission [ Time Frame: 1 year ]
  • Rate of partial cytogenetic remission [ Time Frame: 1 year ]
  • Rate of marrow response [ Time Frame: 1 year ]


Original Secondary Outcome:

  • Rate of complete response (CR) [ Time Frame: 1 year ]
  • Duration of Response [ Time Frame: 1 year ]
  • Rate of progression free survival (PFS) [ Time Frame: 1 year ]
  • Rate of survival [ Time Frame: 1 year ]
  • Number of patients that experience Adverse Events (AEs) [ Time Frame: Until 30 days following end of study ]
  • Rate of complete cytogenetic remission [ Time Frame: 1 year ]
  • Rate of partial cytogenetic remission [ Time Frame: 1 year ]
  • Rate of marrow response [ Time Frame: 1 year ]
  • Rate of clinical benefit [ Time Frame: 1 year ]


Information By: Kura Oncology, Inc.

Dates:
Date Received: June 15, 2016
Date Started: October 2016
Date Completion: April 2019
Last Updated: May 14, 2017
Last Verified: May 2017