Thalidomide, Prednisone, and Cyclophosphamide in Treating Patients With Myelofibrosis and Myeloid Metaplasia
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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 2 |
| Study Type: | Interventional |
| Study Design: | Masking: Open Label Primary Purpose: Treatment |
| 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) |
- 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 ]
- 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 |
| Study Completion Date: | October 2006 |
| Primary Completion Date: | October 2006 (Final data collection date for primary outcome measure) |
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 |
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 More Information
Additional Information:
No publications provided
| Responsible Party: | Ruben A. Mesa, M.D., Mayo Clinic |
| ClinicalTrials.gov Identifier: | NCT00445900 History of Changes |
| Other Study ID Numbers: | CDR0000530973, P30CA015083, MC028A, 1360-03 |
| Study First Received: | March 7, 2007 |
| Last Updated: | March 16, 2011 |
| Health Authority: | United States: Federal Government |
Keywords provided by Mayo Clinic:
|
primary myelofibrosis essential thrombocythemia polycythemia vera secondary myelofibrosis |
Additional relevant MeSH terms:
|
Primary Myelofibrosis Metaplasia Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases Pathologic Processes Cyclophosphamide Thalidomide Prednisone Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses |
Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Anti-Inflammatory Agents Leprostatic Agents Anti-Bacterial Agents Anti-Infective Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents |
ClinicalTrials.gov processed this record on June 17, 2013