Thalidomide, Prednisone, and Cyclophosphamide in Treating Patients With Myelofibrosis and Myeloid Metaplasia

Study Overview
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Brief Summary
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RATIONALE: Giving thalidomide together with prednisone and cyclophosphamide may lessen symptoms caused by myelofibrosis and myeloid metaplasia. PURPOSE: This phase II trial is studying the side effects and how well giving thalidomide together with prednisone and cyclophosphamide works in treating patients with myelofibrosis and myeloid metaplasia.

Detailed Description
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OBJECTIVES: Primary Determine the benefit of thalidomide, prednisone, and cyclophosphamide in alleviating disease-associated anemia, thrombocytopenia, and/or splenomegaly in patients with myelofibrosis with myeloid metaplasia (MMM). Determine the benefit of this regimen in palliating four hypercatabolic constitutional symptoms (i.e., weight loss, fatigue, drenching night sweats, and unexplained fevers) in these patients. Determine the toxicity profile of this regimen in these patients. Secondary Determine the effect of this regimen on leukocyte count. Determine the effect of this regimen on bone marrow histology, including microvessel density and reticulin fibrosis. Determine the effect of this regimen on intramedullary and urinary markers of angiogenesis. Determine the effect of this regimen on circulating myeloid progenitor cells by quantifying CD34+ cells. OUTLINE: Patients receive oral thalidomide, oral prednisone, and oral cyclophosphamide (TPC) once daily on days 1-28. Treatment repeats every 28 days for 3 courses. After 3 courses (3 months) of treatment, patients who respond to TPC therapy may receive oral thalidomide alone once daily for up to 3 months in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspirate and biopsy prior to study entry, 6 months after starting therapy, and then every 6 months for up to 3 years. Samples are analyzed by microvessel density/angiogenesis studies (i.e., CD34 immunohistochemical and vascular endothelium-specific staining) to determine the effect of therapy on markers of bone marrow angiogenesis. After completion of study therapy, patients are followed every 6 months for up to 3 years. PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study.

Official Title
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Phase II Study of the Combination of Low-Dose Thalidomide, Prednisone, and Oral Cyclophosphamide (TPC) in the Therapy of Myelofibrosis With Myeloid Metaplasia (MMM)

Conditions
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Chronic Myeloproliferative Disorders, Secondary Myelofibrosis

Intervention / Treatment
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* Drug: cyclophosphamide
* Drug: prednisone
* Drug: thalidomide
* Other: immunohistochemistry staining method
* Other: laboratory biomarker analysis
* Procedure: biopsy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed myelofibrosis with myeloid metaplasia (MMM) of any of the following subtypes: Agnogenic myeloid metaplasia Post-polycythemic myeloid metaplasia Post-thrombocythemic myeloid metaplasia Must have 1 of the following MMM-related conditions: Anemia, defined as hemoglobin < 10 g/dL Iron deficiency must be excluded as cause Thrombocytopenia, defined as platelet count < 100,000/mm³ Palpable hepatomegaly or splenomegaly No evidence of myelofibrosis-associated conditions in the bone marrow, including any of the following: Metastatic carcinoma Lymphoma Myelodysplasia Hairy cell leukemia Mast cell disease Acute leukemia (including M7 type) Acute myelofibrosis No chromosomal translocation t(9:22) or bcr-abl as determined by bone marrow chromosome analysis or peripheral blood fluorescent in situ hybridization (FISH) analysis PATIENT CHARACTERISTICS: ECOG performance status 0-3 Absolute neutrophil count ≥ 750/mm³ Bilirubin ≤ 2 times upper limit of normal (ULN), unless elevation due to MMM AST ≤ 5 times ULN, unless elevation due to MMM Creatinine ≤ 2.5 mg/dL No uncontrolled infection, including tuberculosis No known history of positive purified protein derivative (PPD) untreated by isoniazid therapy Positive PPD with normal chest X-ray and completion of full-course isoniazid therapy allowed No federal medical center inmates or other incarcerated patients No peripheral neuropathy ≥ grade 2 No comorbid condition in which the use of study therapy is felt to be potentially harmful Not pregnant or nursing Negative pregnancy test Fertile patients must use 2 forms of effective contraception PRIOR CONCURRENT THERAPY: No chemotherapy (e.g., hydroxyurea, myelosuppressive therapy) within the past 14 days Prior splenectomy for MMM allowed No concurrent hematopoietic growth factors

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cyclophosphamide|nan|
|Drug: prednisone|nan|
|Drug: thalidomide|nan|
|Other: immunohistochemistry staining method|nan|
|Other: laboratory biomarker analysis|nan|
|Procedure: biopsy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed response, defined as a complete or partial response in ≥ 1 of 3 response categories (i.e., anemia, thrombocytopenia, or splenomegaly or hepatomegaly) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Constitutional symptom status and bone marrow morphology |  |  | 
| Overall survival |  |  | 
| Progression-free survival |  |  | 
| Time to progression |  |  | 
| Duration of response |  |  | 
| Toxicity as measured by NCI CTC v 2.0 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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primary myelofibrosis, essential thrombocythemia, polycythemia vera, secondary myelofibrosis