Tipifarnib in Subjects With Myelodysplastic Syndromes

NCT02779777 | Terminated Phase 2 Results DMC

• 1 other identifier: KO-TIP-003
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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.

Conditions

Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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.

  1 year

Secondary Outcomes (7)

• Rate of Transfusion Independence

  1 year

• Duration of Transfusion Independence

  1 year

• Hematologic Improvement

  1 year

• Duration of Response

  1 year

• Progression-free Survival (PFS) at 1 Year

  1 year

Study Arms (2)

Regimen 1: Tipifarnib

EXPERIMENTAL

600 mg twice daily (bid) for 7 days on Days 1-7 in 28 day cycles.

Drug: Tipifarnib

Regimen 2: Tipifarnib

EXPERIMENTAL

300 mg bid for 21 days on Days 1-21 in 28 day cycles.

Drug: Tipifarnib

Interventions

Tipifarnib DRUG

Oral tablet

Also known as: Zarnesta

Regimen 1: Tipifarnib; Regimen 2: Tipifarnib

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.
• Documented pathological evidence of MDS as defined by the World Health Organization (WHO) criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
• 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 1. 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
• Acceptable liver function:
• Total or direct bilirubin ≤ 1.5 times upper limit of normal (x ULN); does not apply to subjects with Gilbert's syndrome diagnosed as per institutional guidelines.
• AST (SGOT) and ALT (SGPT) ≤ 2.5 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:

• 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 1.
• 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.
• 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, 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.
• Subjects who have exhibited allergic reactions to tipifarnib, or structural compounds similar to tipifarnib or to its excipients.
• 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 (2)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

tipifarnib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

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

ko-tip-003@kuraoncology.com

+1 617-588-3755

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2016
• First Posted: May 20, 2016
• Study Start: June 1, 2016
• Primary Completion: August 28, 2018
• Study Completion: August 28, 2018
• Last Updated: July 31, 2024
• Results First Posted: July 31, 2024

Record last verified: 2024-07

Locations

US (2)