Thalidomide in Treating Patients With Myelofibrosis

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of thalidomide in treating patients who have myelofibrosis. Thalidomide may stop the growth of myelofibrosis by stopping blood flow to the cancer cells.

Detailed Description
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PRIMARY OBJECTIVES: I. To investigate whether thalidomide, a potent inhibitor of angiogenic and fibrogenic growth factors, is an effective therapeutic agent in patients with MMM. Specifically, to assess whether thalidomide improves anemia and/or organomegaly in patients with MMM. II. To assess the effects of thalidomide on the myelofibrotic stroma with respect to microvascular architecture and angiogenesis, collagen and reticulin deposition, and the expression of the mediating growth factors bFGF, TGF-b, and PDGF, and their respective receptors. OUTLINE: This is a multicenter study. Patients receive oral thalidomide once daily for 1 year in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may receive 1 additional year of therapy. Patients are followed every 6 months until 5 years from study entry.

Official Title
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A Pilot Study of Thalidomide as an Inhibitor of Angiogenesis in the Treatment of Myelofibrosis With Myeloid Metaplasia (MMM)

Conditions
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Primary Myelofibrosis

Intervention / Treatment
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* Drug: thalidomide
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed myelofibrosis with myeloid metaplasia Agnogenic myeloid metaplasia Post-polycythemic myeloid metaplasia Post-thrombocythemic myeloid metaplasia No metastatic carcinoma, lymphoma, myelodysplasia, hairy cell leukemia, mast cell disease, acute leukemia (including M7), or acute myelofibrosis No chromosomal translocation t(9;22) or bcr/abl gene rearrangement Presence of reticulin fibrosis in bone marrow and leukoerythroblastosis and dacrocytosis in peripheral blood Presence of anemia (hemoglobin less than 10 g/dL), palpable splenomegaly, or hepatomegaly Performance status - ECOG 0-2 Absolute neutrophil count greater than 750/mm^3 Platelet count less than 400,000/mm^3 WBC less than 50,000/mm^3 Bilirubin no greater than 2 mg/dL (if total bilirubin elevated, direct bilirubin must be normal) AST no greater than 3 times upper limit of normal (ULN) Alkaline phosphatase no greater than 3 times ULN Creatinine no greater than 1.5 mg/dL Creatinine clearance at least 60 mL/min Not pregnant or nursing Negative pregnancy test Fertile women must use at least 1 highly active method AND 1 additional effective method of contraception for at least 4 weeks before study, during study, and for at least 4 weeks after study Fertile men must use effective contraception during study and for at least 4 weeks after study No uncontrolled infection No concurrent condition that would preclude study No peripheral neuropathy At least 1 month since prior interferon, pirfenidone, anagrelide, or epoetin alfa At least 1 month since prior hydroxyurea or other chemotherapy At least 1 month since prior corticosteroids or androgen derivatives

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (thalidomide)<br>Patients receive oral thalidomide once daily for 1 year in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may receive 1 additional year of therapy. | Drug: thalidomide<br>* Given PO<br>Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed Response, i.e., an objective status of complete or partial response, recorded on 2 consecutive evaluations at least 4 weeks apart. | The proportion of successes will be estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients) and 95% confidence intervals calculated using the Duffy-Santner algorithm for multi-stage designs. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Kaplan-Meier survival curves will be generated to estimate survival. | Number of days from registration date to the date of death or last follow-up, assessed up to 5 years | 
| Time to progression | Kaplan-Meier survival curves will be generated to estimate time to progression. | Number of days from registration date to the date of disease progression or last follow-up, assessed up to 5 years | 
| Response duration | Kaplan-Meier survival curves will be generated to estimate response duration. | Number of days from the first date that objective status = complete or partial response was recorded to the date of disease progression or date of death, whichever comes first, assessed up to 5 years |