Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Tipifarnib in Subjects With Chronic Myelomonocytic Leukemia, Other MDS/MPN, and Acute Myeloid Leukemia (CMML/AML)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02807272
Recruitment Status : Recruiting
First Posted : June 21, 2016
Last Update Posted : October 16, 2019
Sponsor:
Information provided by (Responsible Party):
Kura Oncology, Inc.

Tracking Information
First Submitted Date  ICMJE June 15, 2016
First Posted Date  ICMJE June 21, 2016
Last Update Posted Date October 16, 2019
Study Start Date  ICMJE October 2016
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 14, 2019)
  • To assess the antitumor activity of tipifarnib in CMML subjects [ Time Frame: 1 year ]
    To assess the antitumor activity of tipifarnib, in terms of Objective Response Rate (ORR), in subjects with CMML and in subjects with CMML whose disease is KRAS/NRAS wild type.
  • To assess the antitumor activity of tipifarnib in MDS/MPN subjects [ Time Frame: 1 year ]
    To assess the antitumor activity of tipifarnib, in terms of ORR, in subjects with MDS/MPN, including CMML, who have a high ratio of expression of CXCR4 to CXCR2 (CXCR4/2 ratio) in their bone marrow and in those with low CXCR4/2 ratio.
  • To assess the antitumor activity of tipifarnib in AML subjects [ Time Frame: 1 year ]
    To assess the antitumor activity of tipifarnib, in terms of ORR, in subjects with AML who have a high ratio of expression of CXCR4 to CXCR2 (CXCR4/2 ratio) in their bone marrow and in those with low CXCR4/2 ratio.
Original Primary Outcome Measures  ICMJE
 (submitted: June 16, 2016)
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 14, 2019)
  • Rate of complete response (CR) [ Time Frame: 1 year ]
    To assess the effect of tipifarnib on rate of complete response, complete cytogenetic remission, partial remission, marrow response, and clinical benefit
  • Duration of Response [ Time Frame: 1 year ]
    To assess the effect of tipifarnib on duration of response.
  • Rate of progression free survival (PFS) at 1 year [ Time Frame: 1 year ]
    To assess the effect of tipifarnib on rate of progressive free survival at 1 year.
  • Rate of survival at 1 year [ Time Frame: 1 year ]
    To assess the effect of tipifarnib on rate of survival at 1 year.
  • Adverse event (AE) profile [ Time Frame: Until 30 days following end of study ]
    To assess the effect of tipifarnib on adverse event (AE) profile according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v 4.03).
Original Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2016)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tipifarnib in Subjects With Chronic Myelomonocytic Leukemia, Other MDS/MPN, and Acute Myeloid Leukemia
Official Title  ICMJE A Phase 2 Study of Tipifarnib in Subjects With Chronic Myelomonocytic Leukemia, Other Myelodysplastic /Myeloproliferative Neoplasias, and Acute Myeloid Leukemia
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 (amendment 3 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.
Detailed Description

This Phase 2 study will investigate the antitumor activity in terms of ORR of tipifarnib in subjects with Myelodysplastic/Myeloproliferative Neoplasias (MDS/MPN cohorts) and Acute Myeloid Leukemia (AML cohorts). For MDS/MPN cohorts, this study will assess the antitumor activity of tipifarnib, in terms of ORR, in subjects with MDS/MPN, including CMML, who have a high ratio of expression of CXCR4 to CXCR2 (CXCR4/2 ratio) in their bone marrow and in those with a low CXCR4/2 ratio. For AML cohorts, this study will assess the antitumor activity of tipifarnib, in terms of ORR, in subjects with AML who have a high ratio of expression of CXCR4 to CXCR2 (CXCR4/2 ratio) in their bone marrow and in those with low CXCR4/2 ratio. Subjects enrolled in the study will consist of patients with KRAS, NRAS wild type status.

  1. Subjects with MDS/MPN with high CXCR4/2 ratio
  2. Subjects with MDS/MPN with low CXCR4/2 ratio
  3. Subjects with AML with high CXCR4/2 ratio
  4. Subjects with AML with low CXCR4/2 ratio
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia, Myelomonocytic, Chronic
Intervention  ICMJE Drug: Tipifarnib
Oral tablet
Other Names:
  • R115777
  • Zarnestra
Study Arms  ICMJE Experimental: Tipifarnib, Oral
Single arm
Intervention: Drug: Tipifarnib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 14, 2019)
72
Original Estimated Enrollment  ICMJE
 (submitted: June 16, 2016)
20
Estimated Study Completion Date  ICMJE May 2022
Estimated Primary Completion Date April 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subject is at least 18 years of age.
  2. 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).

  3. For subjects enrolled in the AML cohort:

    1. Documented pathological evidence of AML, as defined by WHO criteria (2008)
    2. 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
  4. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
  5. Subject is willing and able to comply with scheduled visits, treatment plans, laboratory tests and other procedures (including bone marrow assessments).
  6. 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.
  7. Acceptable liver function:

    1. Total bilirubin upper limit of normal (ULN).
    2. AST (SGOT) and ALT (SGPT) 1.5 x ULN.
  8. 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.
  9. Female subjects must be:

    1. Of non-child-bearing potential (surgically sterilized or at least 2 years post-menopausal); or
    2. If of child-bearing potential, subject must use a highly effective method of contraception, such as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomised partner or sexual abstinence. Both females and male subjects with female partners of child-bearing potential must agree to use a highly effective method of contraception for 2 weeks prior to screening, during, and at least 28 days after last dose of trial medication for females and 90 days for males. Female subjects must have a negative serum or urine pregnancy test within 72 hours prior to start of trial medication.
    3. And, not breast feeding at any time during the study.
  10. Written and voluntary informed consent understood, signed and dated.

Exclusion Criteria:

  1. Neoplasia harbours RAS mutation (NRAS mutant, KRAS mutant or double mutant)
  2. Acute promyelocytic leukemia or Bcr-Abl positive leukemia (chronic myelogenous leukemia in blast crisis)
  3. Clinically active CNS leukemia
  4. CMML with t(5;12) that have not yet received imatinib.
  5. Participation in any interventional study within 1 week of randomization or 5 half-lives of the prior treatment agent (whichever is longer).
  6. 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.
  7. Hematopoietic stem cell transplantation (HSCT) performed within 3 months prior to Cycle 1 Day 1.
  8. Concurrent use of granulocyte macrophage colony-stimulating factor (GM-CSF).
  9. Prior treatment (at least 1 full treatment cycle) with a farnesyltransferase inhibitor.
  10. 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.
  11. Major surgery, other than diagnostic surgery, within 2 weeks prior to Cycle 1 Day 1, without complete recovery.
  12. 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).
  13. 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.
  14. 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.
  15. The subject has legal incapacity or limited legal capacity.
  16. Significantly altered mental status that would limit the understanding or rendering of informed consent and compliance with the requirements of this protocol. Unwillingness or inability to comply with the study protocol for any reason.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jeanne Britt 678-777-0686 medicalaffairs@kuraoncology.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02807272
Other Study ID Numbers  ICMJE KO-TIP-004
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Kura Oncology, Inc.
Study Sponsor  ICMJE Kura Oncology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: TBD TBD, TBD
PRS Account Kura Oncology, Inc.
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP