Study of Decitabine Induction Prior to Allogeneic Hematopoietic Cell Transplant in Newly Diagnosed MDS Patients
Prospective Phase II Study of Decitabine Induction Therapy to Reduce Pre-transplant Disease Burden Prior to Allogeneic Hematopoietic Cell Transplant in Patients With Newly Diagnosed Myelodysplastic Syndromes.
Allogeneic blood stem cell transplant remains the only potential curative treatment for myelodysplastic syndromes (MDS) to date. Pre-transplant induction chemotherapy with leukemia-type regimens is associated with significant toxicity and even death. The hypomethylating agents decitabine and 5-azacytidine have been shown in studies to cause improved hematologic parameters and partial or complete responses in patients with high risk MDS compared to standard therapy. In contrast to leukemia-type chemotherapy, decitabine is associated with a relatively low risk of toxicity. We therefore propose to treat transplant-eligible MDS patients with Decitabine as induction therapy and a bridge to transplant.
Hypothesis:
- Decitabine is able to reduce disease burden as measured by blood and marrow blast counts prior to allogeneic hematopoietic stem cell transplant to below 5%.
- Decitabine is well-tolerated by patients with high-risk MDS and will be a safe induction agent and bridge prior to allogeneic transplant in transplant-eligible patients.
Panoramica dello studio
Descrizione dettagliata
Primary endpoint:
- safety and tolerability of Decitabine prior to transplant (assessed by occurence of non-hematologic toxicities of grade 3 or more as defined by CTC grading)
- reduction in pre-transplant disease burden ability to achieve blast <5% in the bone marrow and peripheral blood
Secondary endpoints:
- Proportion of patients with suitable donor able to proceed to an allogeneic hematopoietic cell transplant.
- Non-relapse mortality
- time to neutrophil engraftment
- Overall survival and disease-free survival.
Patients will receive Decitabine until blast <5% is achieved, suitable HLA-matched donor or umbilical cord blood is available up to a maximum of 6 cycles. Patient who progress on therapy or are unable to find a donor by 6 cycles will be removed from protocol. The method, conditioning regimen and choice of donor will be determined based on patient's age and functional status, and transplant physician's discretion. The available regimens are standardized within the center
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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Singapore, Singapore, 169608
- Singapore General Hospital
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Newly diagnosed MDS patients aged 21 to 65 years belonging to any of the following categories: refractory cytopenia with multilineage dysplasia (RCMD) with or without ringed sideroblasts (i.e. RCMD and RCMD-RS), refractory anemia with excess blasts-1 (RAEB-1) or RAEB-2 if the prognostic scores are IPSS (international prognostic scoring system) Int-2 or IPSS-high or with WPSS (WHO prognostic scoring system) 3 and above
- Therapy-related MDS with IPSS Int-2 and above or WPSS 3
- Acceptable cardiac function MUGA or Echocardiography left ventricular ejection fraction of 40% and above
- Acceptable lung function: FEV1>70% predicted, DLCO>60% predicted
- Acceptable renal function: CCT > 50ml/min
- Acceptable liver function: abnormalities in bilirubin or transaminases not > 2times upper limit of normal
- Performance status of ECOG 2 or HCT-specific Comorbidity Index < 3
Exclusion Criteria:
- Any co-morbidity other than MDS which limits life-expectancy to <3mth
- Diagnosis of other active cancer other than squamous cell carcinoma, basal cell carcinoma or carcinoma-in-situ 1 or 2 of the cervix
- Presence of active infections not under control
- Receipt of 5-azacytidine or other induction chemotherapy for MDS/AML
- Patients not keen to explore allogeneic HCT as part of curative treatment plan
- Pregnancy
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
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Sperimentale: Single Arm
Decitabine 20mg/m^2 infusion one hour per day, for 5days,every 28days,total 2-6cycles.
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20mg/m^2 infusion one hour per day, for 5days,every 28days,total 2-6cycles.
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Lasso di tempo |
|---|---|
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Reduction in pre-transplant disease burden
Lasso di tempo: 2 years
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2 years
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Misure di risultato secondarie
Misura del risultato |
Lasso di tempo |
|---|---|
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Sopravvivenza libera da malattia
Lasso di tempo: 3 anni
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3 anni
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Proportion of patients with suitable donor able to proceed to an allogeneic HCT
Lasso di tempo: 2 years
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2 years
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Non-relapse mortality
Lasso di tempo: 3 years
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3 years
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Time to neutrophil engraftment
Lasso di tempo: 2 years
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2 years
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Overall survival survival
Lasso di tempo: 3 years
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3 years
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Collaboratori e investigatori
Sponsor
Collaboratori
Investigatori
- Investigatore principale: Aloysius Ho, Singapore General Hospital
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
- Neoplasie
- Patologia
- Malattie del midollo osseo
- Malattie ematologiche
- Condizioni precancerose
- Sindrome
- Sindromi mielodisplastiche
- Preleucemia
- Meccanismi molecolari dell'azione farmacologica
- Inibitori enzimatici
- Antimetaboliti, Antineoplastici
- Antimetaboliti
- Agenti antineoplastici
- Decitabina
Altri numeri di identificazione dello studio
- Decitabine01
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