Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Biomarker/Laboratory analysis, Treatment	Closed	18 and over	NCI	MAYO-MC028A MAYO-IRB-1360-03, NCT00445900

Objectives

Primary

1. 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).
2. 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.
3. Determine the toxicity profile of this regimen in these patients.

Secondary

1. Determine the effect of this regimen on leukocyte count.
2. Determine the effect of this regimen on bone marrow histology, including microvessel density and reticulin fibrosis.
3. Determine the effect of this regimen on intramedullary and urinary markers of angiogenesis.
4. Determine the effect of this regimen on circulating myeloid progenitor cells by quantifying CD34+ cells.

Entry 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

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

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

Expected Enrollment

A total of 22 patients will be accrued for this study.

Outcomes

Confirmed response, defined as a complete or partial response in ≥ 1 of 3 response categories (i.e., anemia, thrombocytopenia, or splenomegaly or hepatomegaly)

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

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.

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Ruben Mesa, MD, Protocol chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu
Ayalew Tefferi, MD, Protocol co-chair		Ph: 507-538-7623 Email: cancerclinicaltrials@mayo.edu

Registry Information
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)
Trial Start Date		2004-10-28
Registered in ClinicalTrials.gov		NCT00445900
Date Submitted to PDQ		2007-01-11
Information Last Verified		2007-02-27
NCI Grant/Contract Number		CA15083

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