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

Sponsor

Mayo Clinic (Other)

Overall Status

Completed

CT.gov ID

NCT00445900

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders Secondary Myelofibrosis	Drug: cyclophosphamide Drug: prednisone Drug: thalidomide Other: immunohistochemistry staining method Other: laboratory biomarker analysis Procedure: biopsy	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

22 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Oct 1, 2004

Actual Primary Completion Date :

Oct 1, 2006

Actual Study Completion Date :

Oct 1, 2006

Outcome Measures

Primary Outcome Measures

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

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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