Thalidomide, Prednisone, and Cyclophosphamide in Treating Patients With Myelofibrosis and Myeloid Metaplasia
Phase II Study of the Combination of Low-Dose Thalidomide, Prednisone, and Oral Cyclophosphamide ("TPC") in the Therapy of Myelofibrosis With Myeloid Metaplasia (MMM)
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.
Panoramica dello studio
Stato
Descrizione dettagliata
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.
Tipo di studio
Iscrizione (Anticipato)
Fase
- Fase 2
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Mascheramento: Nessuno (etichetta aperta)
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
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Confirmed response, defined as a complete or partial response in ≥ 1 of 3 response categories (i.e., anemia, thrombocytopenia, or splenomegaly or hepatomegaly)
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Misure di risultato secondarie
Misura del risultato |
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Tempo di progressione
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Sopravvivenza libera da progressione
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Sopravvivenza globale
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Durata della risposta
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Constitutional symptom status and bone marrow morphology
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Toxicity as measured by NCI CTC v 2.0
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Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Cattedra di studio: Ruben A. Mesa, MD, Mayo Clinic
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Processi patologici
- Malattie del midollo osseo
- Malattie ematologiche
- Mielofibrosi primaria
- Malattie mieloproliferative
- Metaplasia
- Effetti fisiologici delle droghe
- Meccanismi molecolari dell'azione farmacologica
- Agenti antinfettivi
- Agenti antinfiammatori
- Agenti antireumatici
- Agenti antineoplastici
- Agenti immunosoppressivi
- Fattori immunologici
- Glucocorticoidi
- Ormoni
- Ormoni, sostituti ormonali e antagonisti ormonali
- Agenti antineoplastici, ormonali
- Agenti Antineoplastici, Alchilanti
- Agenti Alchilanti
- Agonisti mieloablativi
- Inibitori dell'angiogenesi
- Agenti di modulazione dell'angiogenesi
- Sostanze per la crescita
- Inibitori della crescita
- Agenti antibatterici
- Agenti leprostatici
- Ciclofosfamide
- Talidomide
- Prednisone
Altri numeri di identificazione dello studio
- CDR0000530973
- P30CA015083 (Sovvenzione/contratto NIH degli Stati Uniti)
- MC028A (Altro identificatore: Mayo Clinic Cancer Center)
- 1360-03 (Altro identificatore: Mayo Clinic IRB)
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