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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)

Phase 2
18 Years
Not Enrolling
Chronic Myeloproliferative Disorders, Secondary Myelofibrosis

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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)



- 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.


- 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

- 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

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

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


- 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)


- 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

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use 2 forms of effective contraception


- 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:


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:


Principal Investigator

Ruben A. Mesa, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Federal Government

Study ID:




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