Thalidomide, Prednisone, and Cyclophosphamide in Treating Patients With Myelofibrosis and Myeloid Metaplasia - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00445900

Purpose

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	Intervention	Phase
Chronic Myeloproliferative Disorders Secondary Myelofibrosis	Drug: cyclophosphamide Drug: prednisone Drug: thalidomide Other: immunohistochemistry staining method Other: laboratory biomarker analysis Procedure: biopsy	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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)

Resource links provided by NLM:

MedlinePlus related topics: Spleen Diseases

Drug Information available for: Cyclophosphamide Thalidomide Prednisone

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

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) [ Designated as safety issue: No ]

Secondary Outcome Measures:

Constitutional symptom status and bone marrow morphology [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Time to progression [ Designated as safety issue: No ]
Duration of response [ Designated as safety issue: No ]
Toxicity as measured by NCI CTC v 2.0 [ Designated as safety issue: Yes ]

Estimated Enrollment:	22
Study Start Date:	October 2004

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00445900

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:	Ruben A. Mesa, MD	Mayo Clinic
Investigator:	Ayalew Tefferi, MD	Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000530973, MAYO-MC028A, MAYO-IRB-1360-03
Study First Received:	March 7, 2007
Last Updated:	May 9, 2009
ClinicalTrials.gov Identifier:	NCT00445900 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

chronic idiopathic myelofibrosis
essential thrombocythemia
polycythemia vera
secondary myelofibrosis

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Anti-Infective Agents
Prednisone
Thalidomide
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Cyclophosphamide
Hormones
Anti-Bacterial Agents
Neoplastic Processes
Pathologic Processes
Metaplasia

Therapeutic Uses
Neoplasm Metastasis
Growth Inhibitors
Angiogenesis Modulating Agents
Alkylating Agents
Myelofibrosis
Antineoplastic Agents, Hormonal
Hematologic Diseases
Growth Substances
Myeloproliferative Disorders
Angiogenesis Inhibitors
Glucocorticoids
Immunosuppressive Agents
Pharmacologic Actions
Myeloid Metaplasia

ClinicalTrials.gov processed this record on February 08, 2010