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

Chronic Myeloproliferative Disorders Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00445900
• Other study ID #: CDR0000530973
• Secondary ID: P30CA015083MC028
• Status: Completed
• Phase: Phase 2
• First received: March 7, 2007
• Last updated: March 16, 2011
• Start date: October 2004
• Est. completion date: October 2006

Study information

• Verified date: March 2011
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: October 2006
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Metaplasia
• Myeloproliferative Disorders
• Primary Myelofibrosis
• Secondary Myelofibrosis

Intervention

Drug:
• cyclophosphamide

• prednisone

• thalidomide

Other:
• immunohistochemistry staining method

• laboratory biomarker analysis

Procedure:
• biopsy

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Confirmed response, defined as a complete or partial response in = 1 of 3 response categories (i.e., anemia, thrombocytopenia, or splenomegaly or hepatomegaly)			No
Secondary	Constitutional symptom status and bone marrow morphology			No
Secondary	Overall survival			No
Secondary	Progression-free survival			No
Secondary	Time to progression			No
Secondary	Duration of response			No
Secondary	Toxicity as measured by NCI CTC v 2.0			Yes