Back to resultsThalidomide, Prednisone, and Cyclophosphamide in Treating Patients With Myelofibrosis and Myeloid Metaplasia
Primary Purpose
Chronic Myeloproliferative Disorders, Secondary Myelofibrosis
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
cyclophosphamide
prednisone
thalidomide
immunohistochemistry staining method
laboratory biomarker analysis
biopsy
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Myeloproliferative Disorders focused on measuring primary myelofibrosis, essential thrombocythemia, polycythemia vera, secondary myelofibrosis
Eligibility 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
Sites / Locations
Outcomes
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)
Secondary Outcome Measures
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
Full Information
NCT ID
NCT00445900
First Posted
March 7, 2007
Last Updated
March 16, 2011
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00445900
Brief Title
Thalidomide, Prednisone, and Cyclophosphamide in Treating Patients With Myelofibrosis and Myeloid Metaplasia
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)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2011
Overall Recruitment Status
Completed
Study Start Date
October 2004 (undefined)
Primary Completion Date
October 2006 (Actual)
Study Completion Date
October 2006 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
4. Oversight
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myeloproliferative Disorders, Secondary Myelofibrosis
Keywords
primary myelofibrosis, essential thrombocythemia, polycythemia vera, secondary myelofibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)
Enrollment
22 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Type
Drug
Intervention Name(s)
thalidomide
Intervention Type
Other
Intervention Name(s)
immunohistochemistry staining method
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Type
Procedure
Intervention Name(s)
biopsy
Primary Outcome Measure Information:
Title
Confirmed response, defined as a complete or partial response in ≥ 1 of 3 response categories (i.e., anemia, thrombocytopenia, or splenomegaly or hepatomegaly)
Secondary Outcome Measure Information:
Title
Constitutional symptom status and bone marrow morphology
Title
Overall survival
Title
Progression-free survival
Title
Time to progression
Title
Duration of response
Title
Toxicity as measured by NCI CTC v 2.0
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ruben A. Mesa, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Study Chair
12. IPD Sharing Statement
Learn more about this trial
Thalidomide, Prednisone, and Cyclophosphamide in Treating Patients With Myelofibrosis and Myeloid Metaplasia
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