Tipifarnib in Treating Patients With Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or Undifferentiated Myeloproliferative Disorders

Phase 1

Completed

• Conditions: Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Recurrent Disease; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Accelerated Phase of Disease; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Phase of Disease
• Interventions: Other: Laboratory Biomarker Analysis; Drug: Tipifarnib

• Registration Number: NCT02210858
• Lead Sponsor: National Cancer Institute (NCI)

Brief Summary

This phase 1-2 trial studies the side effects and how well tipifarnib works in treating patients with chronic myeloid leukemia, chronic myelomonocytic leukemia, or undifferentiated myeloproliferative disorders. Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVES:

* To describe the toxicities of R115777 (tipifarnib) in adult patients with myeloproliferative disorders.

* To assess hematologic responses, including changes in white blood cell count and erythroid responses.

SECONDARY OBJECTIVES:

* To assess bone marrow cytogenetic responses to R115777.

* To analyze for the presence of neuroblastoma (N)/Kirsten rat sarcoma viral oncogene homolog (K-Ras) mutations in patient bone marrow samples.

* To analyze the effect of R115777 on Ras /DnaJ (Hsp40) homolog, subfamily A, member 1(HDJ-2) farnesylation in patient bone marrow/peripheral blood mononuclear cells.

* To analyze the effect of R115777 on mitogen-activated protein (MAP) kinase activation in patient bone marrow mononuclear cells.

* To perform colony forming unit granulocyte-macrophage (CFU-GM) cytotoxicity assays using patients' hematopoietic cells with R115777.

OUTLINE:

Patients receive tipifarnib orally (PO) twice daily (BID) on days 1-21. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients achieving a good hematologic response may continue treatment at the discretion of the treating physician.

Study Timeline

• Study Start: 2000-05
• Primary Completion: 2004-11-12
• Study First Submitted: 2014-08-05
• Study First Submitted QC: 2014-08-05
• Study First Posted: 2014-08-07
• Study Completion: 2017-03
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-31
• Last Update Posted: 2018-06-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (tipifarnib)	Laboratory Biomarker Analysis	Patients receive tipifarnib PO BID on days 1-21. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Treatment (tipifarnib)	Tipifarnib	Patients receive tipifarnib PO BID on days 1-21. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
WBC response (complete response, defined as normalization of WBC count in patients with an elevated WBC count prior to treatment and partial response, defined as > 50% reduction in WBC count without normalization of WBC count)	Up to 16 weeks	For all hematologic responses, the duration of response must be at least 2 months.
Erythroid response in non-transfusion dependent patients	Up to 16 weeks	Major response is defined as a \> 2.0 g/dL rise in the hemoglobin after 2 to 4 cycles of therapy. Minor response is defined as a \> 1.0 to \< 2.0 g/dL rise in the hemoglobin after 2 to 4 cycles of therapy.
Incidence of adverse events related to tipifarnib assessed by National Cancer Institute Common Toxicity version 2.0	Up to 16 weeks
Erythroid response in transfusion-dependent patients	Up to 16 weeks	Major response is defined as transfusion-independent after 2 to 4 cycles of therapy or a \> 2.0 g/dL rise in hemoglobin without transfusion. Minor response is defined as \> 1 to \< 2.0 g/dL incremental rise in hemoglobin with a decrease in transfusion requirements of at least 50% compared to the mean transfusion requirement during the 8-week pre-study period.

Secondary Outcome Measures

Name	Time	Method
In vitro correlative studies (including N/K-Ras mutation analysis, N/K-Ras/HDJ-2 farnesylation, MAP kinase activation, and bone marrow CFU-GM cytotoxicity assays using tipifarnib with patients' hematopoietic cells)	Up to week 3 (course 4)
Cytogenetic response (including Philadelphia chromosome-positive cells in metaphases in CML)	Up to 16 weeks

Trial Locations

Locations (2)

Stanford Cancer Institute; 🇺🇸 Palo Alto, California, United States

University of Rochester; 🇺🇸 Rochester, New York, United States