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

NCT ID: NCT02210858

Last Updated: 2018-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-05-31
• Study Completion Date: 2017-03-31

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Tipifarnib

Intervention Type: DRUG

Given PO

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Tipifarnib

Given PO

Intervention Type: DRUG

Other Intervention Names

R115777; Zarnestra

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Peter Greenberg

Role: PRINCIPAL_INVESTIGATOR

Stanford Cancer Institute

Locations

Stanford Cancer Institute

Palo Alto, California, United States

University of Rochester

Rochester, New York, United States

Countries

United States

Other Identifiers

NCI-2014-01606

Identifier Type: REGISTRY

Identifier Source: secondary_id

SUMC-NCI-38

Identifier Type: -

Identifier Source: secondary_id

NCI-38

Identifier Type: -

Identifier Source: secondary_id

CDR0000067864

Identifier Type: -

Identifier Source: secondary_id

CTEP 38

Identifier Type: OTHER

Identifier Source: secondary_id

38

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA124435

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB-13343

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-2014-01606

Identifier Type: -

Identifier Source: org_study_id

NCT00005846

Identifier Type: -

Identifier Source: nct_alias