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

NCT ID: NCT00445900

Last Updated: 2011-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-31
• Study Completion Date: 2006-10-31

Brief Summary

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

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.

Conditions

Chronic Myeloproliferative Disorders; Secondary Myelofibrosis

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

cyclophosphamide

Intervention Type: DRUG

prednisone

Intervention Type: DRUG

thalidomide

Intervention Type: DRUG

immunohistochemistry staining method

Intervention Type: OTHER

laboratory biomarker analysis

Intervention Type: OTHER

biopsy

Intervention Type: PROCEDURE

Eligibility Criteria

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Mayo Clinic

Principal Investigators

Ruben A. Mesa, MD

Role: STUDY_CHAIR

Mayo Clinic

Other Identifiers

P30CA015083

Identifier Type: NIH

Identifier Source: secondary_id

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MC028A

Identifier Type: OTHER

Identifier Source: secondary_id

1360-03

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000530973

Identifier Type: -

Identifier Source: org_study_id