Tipifarnib in Subjects With Chronic Myelomonocytic Leukemia, Other MDS/MPN, and Acute Myeloid Leukemia

NCT02807272 | Completed Phase 2 Results DMC

• 1 other identifier: KO-TIP-004
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 8

Brief Summary

A Phase 2 study to investigate the antitumor activity in terms of overall response rate (ORR) of tipifarnib in approximately 36 eligible subjects with Myelodysplastic/Myeloproliferative Neoplasias (MDS/MPN), including Chronic Myelomonocytic Leukemia (CMML), and 36 eligible subjects with Acute Myeloid Leukemia (AML). Subjects received tipifarnib 1200 mg to be taken orally with food, twice daily, for 7 days in alternating weeks (Days 1 to 7 and Days 15 to 21) in 28-day cycles. Following amendment 3 subjects (Cohorts 1-4) will receive tipifarnib administered at a dose of 400 mg, orally with food, twice a day (bid) for 21 days in 28-day cycles.

Conditions

Leukemia, Myelomonocytic, Chronic

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The ORR was estimated based on the number of participants who achieved an objective response (OR) (complete response \[CR\], complete cytogenetic remission \[CCR\], partial remission \[PR\], marrow response \[MR\], or clinical benefit \[CB\] performed by Principal Investigator according to the MDS/MPN International Working Group \[IWG\] criteria).

  Up to 12 months

Secondary Outcomes (4)

• Duration of Response (DoR)

  Up to approximately 15 months

• Progression Free Survival (PFS)

  1 year

• Overall Survival (OS)

  Up to approximately 15 months

• Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)

  Up to approximately 3 years

Study Arms (1)

Tipifarnib, Oral

EXPERIMENTAL

Single arm

Drug: Tipifarnib

Interventions

Tipifarnib DRUG

Oral tablet

Also known as: R115777, Zarnestra

Tipifarnib, Oral

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is at least 18 years of age.
• For subjects to be enrolled in the CMML or MDS/MPN cohorts:
• a. Diagnosis of CMML or MDS/MPN as defined by the World Health Organization (WHO) criteria (2008).
• For subjects enrolled in the AML cohort:
• Documented pathological evidence of AML, as defined by WHO criteria (2008)
• Refractory to previous induction chemotherapy, relapsed disease, or age ≥ 60 and not appropriate for standard cytotoxic therapy due to age, performance status, and/or adverse risk factors according to the treating physician
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
• 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 1. Subjects on a stable dose of hydroxyurea for at least 2 weeks prior to Cycle 1 Day 1 may continue on hydroxyurea until Cycle 1 Day 14. 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 liver function:
• Total bilirubin ≤ upper limit of normal (ULN).
• AST (SGOT) and ALT (SGPT) ≤ 1.5 x ULN.
• Acceptable renal function with serum creatinine ≤ 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault or Modification of Diet in Renal Disease formulas.
• Female subjects must be:
• Of non-child-bearing potential (surgically sterilized or at least 2 years post-menopausal); or

You may not qualify if:

• Neoplasia harbours RAS mutation (NRAS mutant, KRAS mutant or double mutant)
• Acute promyelocytic leukemia or Bcr-Abl positive leukemia (chronic myelogenous leukemia in blast crisis)
• Clinically active CNS leukemia
• CMML with t(5;12) that have not yet received imatinib.
• Participation in any interventional study within 1 week of randomization or 5 half-lives of the prior treatment agent (whichever is longer).
• Ongoing treatment with an anticancer agent for CMML, MDS/MPN or AML not contemplated in this protocol. Subjects on a stable dose of hydroxyurea for at least 2 weeks prior to Cycle 1 Day 1 may continue on hydroxyurea until Cycle 1 Day 14.
• Hematopoietic stem cell transplantation (HSCT) performed within 3 months prior to Cycle 1 Day 1.
• Concurrent use of granulocyte macrophage colony-stimulating factor (GM-CSF).
• Prior treatment (at least 1 full treatment cycle) with a farnesyltransferase inhibitor.
• 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.
• Active, concurrent malignancy requiring radiation, chemotherapy, or immunotherapy (excluding non-melanoma skin cancer, adjuvant hormonal therapy for breast cancer and hormonal treatment for castration sensitive prostate cancer).
• Active and uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy. Known infection with human immunodeficiency virus (HIV), or an active infection with hepatitis B or hepatitis C.
• 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.

Sponsors & Collaborators

• Kura Oncology, Inc.: lead

Study Sites (8)

Mayo Clinic Arizona

Scottsdale, Arizona, 85054, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

H. Lee Moffitt Cancer Center & Research Institute, Inc.

Tampa, Florida, 33612, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic

Interventions

tipifarnib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Clinical Operations
• Organization: Kura Oncology Inc.

KO-TIP-004@kuraoncology.com

+1 617 588-3755

Study Officials

• TBD TBD, TBD

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2016
• First Posted: June 21, 2016
• Study Start: January 10, 2017
• Primary Completion: November 30, 2020
• Study Completion: November 30, 2020
• Last Updated: July 17, 2024
• Results First Posted: July 17, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)