- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02807272
Tipifarnib in Subjects With Chronic Myelomonocytic Leukemia, Other MDS/MPN, and Acute Myeloid Leukemia (CMML/AML)
A Phase 2 Study of Tipifarnib in Subjects With Chronic Myelomonocytic Leukemia, Other Myelodysplastic /Myeloproliferative Neoplasias, and Acute Myeloid Leukemia
Study Overview
Status
Conditions
Intervention / Treatment
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.
- Subjects with MDS/MPN with high CXCR4/2 ratio
- Subjects with MDS/MPN with low CXCR4/2 ratio
- Subjects with AML with high CXCR4/2 ratio
- Subjects with AML with low CXCR4/2 ratio
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Arizona
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Scottsdale, Arizona, United States, 85054
- Mayo Clinic Arizona
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Florida
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Jacksonville, Florida, United States, 32224
- Mayo Clinic Florida
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Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center & Research Institute, Inc.
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Maryland
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Baltimore, Maryland, United States, 21231
- Johns Hopkins University
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic Rochester
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New York
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New York, New York, United States, 10065
- Weill Cornell Medicine
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Ohio
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Cleveland, Ohio, United States, 44195
- Cleveland Clinic
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
- 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.
- And, not breast feeding at any time during the study.
- Written and voluntary informed consent understood, signed and dated.
Exclusion Criteria:
- 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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Tipifarnib, Oral
Single arm
|
Oral tablet
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
To assess the antitumor activity of tipifarnib in CMML subjects
Time Frame: 1 year
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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.
|
1 year
|
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.
|
1 year
|
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.
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Rate of complete response (CR)
Time Frame: 1 year
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To assess the effect of tipifarnib on rate of complete response, complete cytogenetic remission, partial remission, marrow response, and clinical benefit
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1 year
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Duration of Response
Time Frame: 1 year
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To assess the effect of tipifarnib on duration of response.
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1 year
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Rate of progression free survival (PFS) at 1 year
Time Frame: 1 year
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To assess the effect of tipifarnib on rate of progressive free survival at 1 year.
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1 year
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Rate of survival at 1 year
Time Frame: 1 year
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To assess the effect of tipifarnib on rate of survival at 1 year.
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1 year
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Adverse event (AE) profile
Time Frame: Until 30 days following end of study
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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).
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Until 30 days following end of study
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: TBD TBD, TBD
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- KO-TIP-004
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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