Tipifarnib in Treating Patients With Myelofibrosis and Myeloid Metaplasia

Primary Myelofibrosis Clinical Trial

Official title:

A Phase II Trial of R115777 in Myelofibrosis With Myeloid Metaplasia (MMM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00047190
• Other study ID #: NCI-2012-02804
• Secondary ID: MC0184N01CM17104
• Status: Completed
• Phase: Phase 2
• First received: October 3, 2002
• Last updated: June 3, 2013
• Start date: August 2002

Study information

• Verified date: June 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

PRIMARY OBJECTIVES:

I. To evaluate the response rate in MMM patients treated with R115777. II. To evaluate the toxicity of R115777 in patients with MMM.

SECONDARY OBJECTIVES:

I. To evaluate the benefit of therapy with R115777 in alleviating disease-associated anemia in patients with MMM.

II. To evaluate the benefit of R115777 in reducing palpable splenomegaly in patients with MMM.

III. To evaluate the effect of R115777 on the hypercatabolic symptoms from MMM. IV. To evaluate the effect of R115777 on the pathologic increase in circulating myeloid progenitors in MMM patients through baseline measurement and measurement after the first cycle.

V. To correlate response/relapse with in vitro myeloid colony sensitivity to R115777 at the time of either response or relapse.

VI. To evaluate the effect of R115777 on bone marrow histologic features of MMM including osteosclerosis, reticulin fibrosis, and angiogenesis (through serial bone marrow microvessel density grading).

OUTLINE: This is a multicenter study.

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.

Patients are followed every 3 months until disease progression and then every 6 months for up to 2 years.

PROJECTED ACCRUAL: A total of 18-35 patients will be accrued for this study within 15 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. primary completion date: April 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Essential Thrombocythemia
• Metaplasia
• Polycythemia
• Polycythemia Vera
• Primary Myelofibrosis
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• tipifarnib
Given PO

Other:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Overall survival	Estimated using the method of Kaplan-Meier.	Time from registration to death due to any cause, assessed up to 2 years	No
Secondary	Time to progression	Estimated using the method of Kaplan-Meier.	Time from registration to the time of progression, assessed up to 2 years	No
Secondary	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	No