COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

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

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. Read our disclaimer for details. Identifier: NCT02210858
Recruitment Status : Completed
First Posted : August 7, 2014
Last Update Posted : June 4, 2018
Information provided by (Responsible Party):
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.

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

Detailed Description:


  • 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Arm Intervention/treatment
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
Correlative studies

Drug: Tipifarnib
Given PO
Other Names:
  • R115777
  • Zarnestra

Primary Outcome Measures :
  1. 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.

  2. 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.

  3. Incidence of adverse events related to tipifarnib assessed by National Cancer Institute Common Toxicity version 2.0 [ Time Frame: Up to 16 weeks ]
  4. 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.

Secondary Outcome Measures :
  1. Cytogenetic response (including Philadelphia chromosome-positive cells in metaphases in CML) [ Time Frame: Up to 16 weeks ]
  2. 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) ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes


  • Patients with a diagnosis (> 3 months prior to enrollment) of:

    • Chronic myeloid leukemia (CML) (Philadelphia chromosome positive or polymerase chain reaction [PCR] positive for breakpoint cluster region [BCR]-Abelson murine leukemia viral oncogene homolog 1 [ABL]) in chronic phase with:

      • Persistent or progressive disease on maximum tolerated interferon therapy, or STI571 (if eligible and able to receive this drug), as evidenced by increasing white blood cell (WBC) count, peripheral blood myeloid immaturity and/or progressive anemia, and/or persistence or relapse of abnormal cytogenetic and/or molecular findings
      • Interferon or STI571 intolerant
    • CML (Philadelphia chromosome positive or PCR positive for BCR-ABL) in accelerated phase (< 20% blasts in the peripheral blood and bone marrow) with persistent or progressive disease on STI571 (if eligible and able to receive this drug)
    • CML patients are eligible if they have not received interferon or STI571 because they are allergic to these drugs or refuse their use
  • Chronic myelomonocytic leukemia (CMML)

    • Proliferative-type (WBC > 12,000/mL)
    • Less than 5% blasts in the peripheral blood and < 20% blasts in the bone marrow
  • Undifferentiated myeloproliferative disorder (UMPD)
  • Atypical (i.e. Philadelphia chromosome-negative) CML
  • Four weeks must have elapsed since the use of any previous pharmacotherapy including interferon, hematopoietic growth factors, and cytotoxic chemotherapy (6 weeks for prior mitomycin or nitrosoureas); hydroxyurea may be used to manage elevated cell counts in patients up to the time they begin investigational therapy
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Patients are capable of swallowing capsules
  • Total bilirubin is > 1.5 X the upper limit of normal (ULN) where the analysis is performed; for example, for Stanford University Hospital, the ULN for total bilirubin is 1.3
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) are > 2 X the ULN; for example, for Stanford University Hospital, the ULN for ALT is 35, and the ULN for AST is 41
  • Serum creatinine of < 2.0
  • Life expectancy > 4 months
  • Written inform consent must be obtained


  • Blast crisis phase of CML and atypical CML/ undifferentiated myeloproliferative disorders
  • Patients with > 20% blasts in the peripheral blood or bone marrow are excluded
  • Prior allogeneic bone marrow transplantation
  • Patients with severe disease other than CML, CMML, or UMPD which is expected to prevent compliance with the protocol
  • Patients with septicemia or other severe infections
  • Pregnant or breast-feeding females
  • Women of reproductive age should use contraception while on study
  • Patients may not receive androgens during the study
  • Requirement for ongoing therapy with corticosteroids (> 10 mg/d prednisone or equivalent steroid dosage) other than as pre-medication for transfusions
  • Patients with iron deficiency; if a marrow aspirate is not available, transferrin saturation must be > 20% and serum ferritin > 50 ng/mL; this exclusion criterion will be removed if the iron deficiency state is corrected before enrollment
  • Patients with other contributing causes of anemia such as autoimmune or hereditary hemolytic disorders, gastrointestinal (GI) blood loss, B12 or folate deficiency, or hypothyroidism; patients who require platelet transfusions, or have thrombocytopenia-related bleeding
  • Inability to return for follow-up visits/studies to assess toxicity and response to therapy

Information from the National Library of Medicine

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 identifier (NCT number): NCT02210858

Layout table for location information
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
Sponsors and Collaborators
National Cancer Institute (NCI)
Layout table for investigator information
Principal Investigator: Peter Greenberg Stanford Cancer Institute
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI) Identifier: NCT02210858    
Obsolete Identifiers: NCT00005846
Other Study ID Numbers: NCI-2014-01606
NCI-2014-01606 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CTEP 38 ( Other Identifier: Stanford Cancer Institute )
38 ( Other Identifier: CTEP )
P30CA124435 ( U.S. NIH Grant/Contract )
IRB-13343 ( Other Identifier: Stanford IRB )
First Posted: August 7, 2014    Key Record Dates
Last Update Posted: June 4, 2018
Last Verified: May 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Antineoplastic Agents