Thalidomide in Treating Patients With Myelofibrosis

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.

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