Clinical Trial 18815

Cancer Type: Malignant Hematology
Interventions:Zarnestra (tipifarnib); tipifarnib

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Eric Padron

Overview

Study Title

A Phase 2 Study of Tipifarnib in Subjects with Chronic Myelomonocytic Leukemia

Summary

The main purpose of this study is to see how effective an investigational new drug (tipifarnib, the study drug) is to treat this cancer. Tipifarnib is a study drug that works inside some cancer cells leading them to die or to stop them from growing. "Investigational" means that tipifarnib has not yet been approved by regulatory authorities such as the United States Food and Drug Administration (FDA) for use outside of clinical trials. Other reasons for conducting the study are: - To determine for how long tipifarnib may reduce the size or slow down the growth of your tumor. - To determine the side effects of tipifarnib. - To study your cancer and determine why it responds or not to treatment with tipifarnib.

Objective

Primary Objective: To assess the antitumor activity of tipifarnib, in terms of Objective Response Rate (ORR), of tipifarnib in subjects with chronic myelomonocytic leukemia (CMML) and in subjects with CMML whose disease is KRAS/NRAS wild type. Secondary Objective: To assess the effect of tipifarnib on the following: Rate of complete response (CR), complete cytogenetic remission, partial remission, marrow response, and clinical benefit. Duration of Response. Rate of progression free survival (PFS) at 1 year. Rate of survival at 1 year. Adverse event (AE) profile according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v 4.03). Exploratory Objective: To explore potential biomarkers and their association with clinical benefit from tipifarnib including cancer gene mutations, killer cell immunoglobulin-like receptor (KIR) genotyping, immune cell subsets and other candidate biomarkers of tipifarnib in bone marrow, blood and serum samples.

Inclusion Criteria

  • Diagnosis of chronic myelomonocytic leukemia (CMML) as defined by the World Health Organization (WHO) criteria.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • 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. Participants 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 7. Must have recovered to NCI CTCAE v. 4.03 > Acceptable liver function
  • Acceptable renal function
  • Females of childbearing potential and males with female partners of child-bearing potential must agree to use an adequate method of contraception for 2 weeks prior to screening, during, and at least 4 weeks after last dose of study medication. Female subjects must have a negative serum or urine pregnancy test within 72 hours prior to start of study medication.
  • Not breast feeding at any time during the study.
  • Written and voluntary informed consent understood, signed and dated.

  • Exclusion Criteria

  • Known prior progression to acute myeloid leukemia (AML) defined by at least 20% blasts in the blood or bone marrow.
  • Myeloproliferative/myelodysplastic syndrome other than CMML. CMML with t(5;12) that have not yet received imatinib.
  • Participation in any interventional study within 4 weeks of randomization or 5 half-lives of the prior treatment agent (whichever is longer).
  • Ongoing treatment with an anticancer agent for CMML not contemplated in this protocol. Participants 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 7.
  • 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 participant in this study.
  • The participant 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.