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

Not Recruiting

Trial ID: NCT00005846


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.

Official Title

Phase I/II Study of Tipifarnib [Zarnestra, Farnesyltransferase Inhibitor R115777 (NSC 702818)] in Patients With Myeloproliferative Disorders

Stanford Investigator(s)

Peter Greenberg
Peter Greenberg

Professor of Medicine (Hematology), Emeritus



   - 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

   - 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


drug: tipifarnib

other: Laboratory Biomarker Analysis

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305