Tipifarnib in Treating Patients With Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or Undifferentiated Myeloproliferative Disorders
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|ClinicalTrials.gov Identifier: NCT02210858|
Recruitment Status : Completed
First Posted : August 7, 2014
Last Update Posted : June 4, 2018
|Condition or disease||Intervention/treatment||Phase|
|Accelerated Phase of Disease Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative Chronic Myelogenous Leukemia, BCR-ABL1 Positive Chronic Myelomonocytic Leukemia Chronic Phase of Disease Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable Recurrent Disease||Other: Laboratory Biomarker Analysis Drug: Tipifarnib||Phase 1 Phase 2|
- 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.
- 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.
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Study of Tipifarnib [Zarnestra, Farnesyltransferase Inhibitor R115777 (NSC 702818)] in Patients With Myeloproliferative Disorders|
|Actual Study Start Date :||May 2000|
|Actual Primary Completion Date :||November 12, 2004|
|Actual Study Completion Date :||March 2017|
Experimental: Treatment (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.
Other: Laboratory Biomarker Analysis
- Erythroid response in non-transfusion dependent patients [ Time Frame: 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.
- Erythroid response in transfusion-dependent patients [ Time Frame: 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.
- Incidence of adverse events related to tipifarnib assessed by National Cancer Institute Common Toxicity version 2.0 [ Time Frame: Up to 16 weeks ]
- 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) [ Time Frame: Up to 16 weeks ]For all hematologic responses, the duration of response must be at least 2 months.
- Cytogenetic response (including Philadelphia chromosome-positive cells in metaphases in CML) [ Time Frame: Up to 16 weeks ]
- 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) [ Time Frame: Up to week 3 (course 4) ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02210858
|United States, California|
|Stanford Cancer Institute|
|Palo Alto, California, United States, 94304|
|United States, New York|
|University of Rochester|
|Rochester, New York, United States, 14642|
|Principal Investigator:||Peter Greenberg||Stanford Cancer Institute|