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.
Studieoversigt
Detaljeret beskrivelse
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
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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Singapore, Singapore, 169608
- Singapore General Hospital
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: 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.
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Reduction in pre-transplant disease burden
Tidsramme: 2 years
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2 years
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Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Sygdomsfri overlevelse
Tidsramme: 3 år
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3 år
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Proportion of patients with suitable donor able to proceed to an allogeneic HCT
Tidsramme: 2 years
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2 years
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Non-relapse mortality
Tidsramme: 3 years
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3 years
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Time to neutrophil engraftment
Tidsramme: 2 years
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2 years
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Overall survival survival
Tidsramme: 3 years
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3 years
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Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Aloysius Ho, Singapore General Hospital
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- Decitabine01
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