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

NCT02210858 | Completed Phase 1 DMC FDA Drug

• 8 other identifiers: NCI-2014-01606SUMC-NCI-38NCI-38CDR0000067864CTEP 3838P30CA124435IRB-13343
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (4)

• Erythroid response in non-transfusion dependent patients

  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.

  Up to 16 weeks

• Erythroid response in transfusion-dependent patients

  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.

  Up to 16 weeks

• Incidence of adverse events related to tipifarnib assessed by National Cancer Institute Common Toxicity version 2.0

  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)

  For all hematologic responses, the duration of response must be at least 2 months.

  Up to 16 weeks

Secondary Outcomes (2)

• Cytogenetic response (including Philadelphia chromosome-positive cells in metaphases in CML)

  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)

  Up to week 3 (course 4)

Study Arms (1)

Treatment (tipifarnib)

EXPERIMENTAL

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; Drug: Tipifarnib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (tipifarnib)

Tipifarnib DRUG

Given PO

Also known as: R115777, Zarnestra

Treatment (tipifarnib)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Stanford Cancer Institute

Palo Alto, California, 94304, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myelomonocytic, Chronic; Myeloproliferative Disorders; Recurrence

Interventions

tipifarnib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Peter Greenberg

  Stanford Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2014
• First Posted: August 7, 2014
• Study Start: May 1, 2000
• Primary Completion: November 12, 2004
• Study Completion: March 1, 2017
• Last Updated: June 4, 2018

Record last verified: 2018-05

Locations

US (2)