Phase II Study of the Combination of Low-Dose Thalidomide, Prednisone, and Oral Cyclophosphamide ("TPC") in the Therapy of Myelofibrosis With Myeloid Metaplasia (MMM)
18 Years
N/A
Both
Chronic Myeloproliferative Disorders, Secondary Myelofibrosis
Trial Information
Phase II Study of the Combination of Low-Dose Thalidomide, Prednisone, and Oral Cyclophosphamide ("TPC") in the Therapy of Myelofibrosis With Myeloid Metaplasia (MMM)
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Confirmed response, defined as a complete or partial response in ≥ 1 of 3 response categories (i.e., anemia, thrombocytopenia, or splenomegaly or hepatomegaly)
Safety Issue:
No
Principal Investigator
Ruben A. Mesa, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Mayo Clinic
Authority:
United States: Federal Government
Study ID:
CDR0000530973
NCT ID:
NCT00445900
Start Date:
October 2004
Completion Date:
October 2006
Related Keywords:
- Chronic Myeloproliferative Disorders
- Secondary Myelofibrosis
- primary myelofibrosis
- essential thrombocythemia
- polycythemia vera
- secondary myelofibrosis
- Primary Myelofibrosis
- Metaplasia
- Myeloproliferative Disorders
Name | Location |
|---|
