Tipifarnib in Treating Patients With Myelofibrosis and Myeloid Metaplasia

NCT00047190 | Completed Phase 2

• 3 other identifiers: NCI-2012-02804MC0184N01CM17104
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Phase II trial to study the effectiveness of tipifarnib in treating patients who have myelofibrosis with myeloid metaplasia. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

Conditions

Essential Thrombocythemia; Polycythemia Vera; Primary Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• Confirmed response defined as the objective status of complete response (CR) or partial response (PR) on 2 consecutive evaluations at least 4 weeks apart

  Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner.

  Up to 2 years

Secondary Outcomes (3)

• Overall survival

  Time from registration to death due to any cause, assessed up to 2 years

• Time to progression

  Time from registration to the time of progression, assessed up to 2 years

• Duration of response

  Date of complete response to the date progression is documented (if one has occurred) or to the date of last follow-up (for those patients who have not progressed), assessed up to 2 years

Study Arms (1)

Arm I

EXPERIMENTAL

Patients receive oral tipifarnib twice daily on days 1-21. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: tipifarnib; Other: laboratory biomarker analysis

Interventions

tipifarnib DRUG

Given PO

Also known as: R115777, Zarnestra

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologic confirmation (on bone marrow trephine and aspirate) of myelofibrosis with myeloid metaplasia by a pathologist/hematologist at the registering institution; included in the diagnosis of MMM are AMM (agnogenic myeloid metaplasia), PPMM (post-polycythemic myeloid metaplasia), and PTMM (post-thrombocythemic myeloid metaplasia); the bone marrow should show the presence of reticulin fibrosis, and the peripheral blood smear should show the presence of leukoerythroblastosis and dacrocytosis
• Bone marrow showing no evidence of other conditions associated with myelofibrosis, such as metastatic carcinoma, lymphoma, myelodysplasia, hairy cell leukemia, mast cell disease, acute leukemia (including M7 type), or acute myelofibrosis
• Bone marrow chromosome analysis or peripheral blood or bone marrow Fluorescent In Situ Hybridization (FISH) showing absence of chromosomal translocation t(9:22); prior demonstration is sufficient for enrollment purposes
• At least one of the following:
• Anemia evidenced by hemoglobin \< 10 g/dL
• Palpable hepato-splenomegaly
• ANC ≥ 750/mm\^3
• PLT ≥ 100,000/mm\^3
• Total bilirubin (direct if total elevated) ≤ UNL
• Alkaline phosphatase =\< 3 x UNL (unless felt to be secondary to disease)
• AST ≤ 2.5 x UNL
• Creatinine =\< 1.5 x UNL
• Ability to understand and the willingness to sign a written informed consent document
• Willingness to follow the schedule for returning to the registering P2C institution (monthly) while receiving protocol treatment
• ECOG performance status 0, 1, or 2

You may not qualify if:

• Any of the following as this regimen may be harmful to a developing fetus or nursing child:
• Pregnant women
• Breastfeeding women
• Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, subcutaneous implants, or abstinence, etc.)
• NOTE: The effects of the agent(s) on the developing human fetus at the recommended therapeutic dose are unknown
• Use of cytotoxic chemotherapy or other myelosuppressive agents within =\< 2 weeks prior to study entry
• Uncontrolled intercurrent illness or any co-morbid condition that would limit compliance with study requirements or with which the use of R115777 is felt to be potentially harmful; such conditions include, but are not limited to:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia, or
• Psychiatric illness/social situations
• Other concurrent therapy directed at the disease (including Thalidomide) or use of erythropoietin while enrolled in this study; such agents must be discontinued at the time of or prior to study entry
• Known quinolone sensitivity

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Thrombocythemia, Essential; Polycythemia Vera; Primary Myelofibrosis

Interventions

tipifarnib

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombocytosis; Blood Platelet Disorders; Myeloproliferative Disorders; Bone Marrow Diseases; Hemorrhagic Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms

Study Officials

• Ruben Mesa

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2002
• First Posted: January 27, 2003
• Study Start: August 1, 2002
• Primary Completion: April 1, 2007
• Last Updated: June 4, 2013

Record last verified: 2013-06

Locations

US (1)