Hematopoietic Cell Transplantation With Post-transplantation Cyclophosphamide in MDS

Study Overview
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Brief Summary
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This study is conducted to evaluate the feasibility and efficacy of post-transplantation cyclophosphamide with myeloablative or reduced-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndrome (MDS).

Detailed Description
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Conditioning regimen A) Busulfan 3.2 mg/kg/day i.v. daily For 4 days (days -7 to -4) in patients aged < 55 years For 2 days (days -7 and -6) in patients aged ≥ 55 years B) Fludarabine 30 mg/m2/day i.v. daily on days -7 to -2 (for 6 days) Harvest and infusion of donor hematopoietic cells Harvested peripheral blood mononuclear cells of donors via leukapheresis will be infused to recipients on day 0. Additional infusion on day 1 can be made based on the judgement of attending physician. GVHD prophylaxis A) Cyclophosphamide 50 mg/kg/day i.v. daily on days 3 and 4 (for 2 days) B) Cyclosporine: 1.5 mg/kg i.v. every 12 h hours beginning on day 5 and changed to oral dosing when oral intake is possible. If there is no evidence of GVHD, the dosage will be tapered beginning on day 90 and discontinued on day 180. C) MMF: 15 mg/kg p.o. 3 times daily with a maximum daily dose of 3.0 g beginning on day 5 If there is no active GVHD, Cyclosporine and MMF will be discontinued without taper at day 180 and 35, respectively.

Official Title
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Allogeneic Hematopoietic Cell Transplantation Using Post-transplantation Cyclophosphamide in Myelodysplastic Syndrome Patients

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MDS defined by WHO classification, chronic myelomonocytic leukemia (CMML), or acute myeloid leukemia (AML) evolving from MDS A. IPSS > 1.0 or bone marrow blast ≥ 5% at any time points before HCT or B. AML progressed from MDS or C. CMML Patients receiving first HCT Patients with appropriate hematopoietic cell donors A. HLA-matched sibling donor B. Unrelated donor C. HLA-mismatched familial donor 15 years old or older Adequate performance status (Karnofsky score of 70 or more) Adequate hepatic and renal function (AST, ALT, and bilirubin < 3.0 x upper normal limit, and creatinine < 2.0 mg/dL). Adequate cardiac function (left ventricular ejection fraction over 40% on heart scan or echocardiogram Signed and dated informed consent must be obtained from both recipient and donor. Exclusion Criteria: Presence of significant active infection Presence of uncontrolled bleeding Any coexisting major illness or organ failure Patients with psychiatric disorder or mental deficiency severe as to make compliance with the treatment unlike, and making informed consent impossible Nursing women, pregnant women, women of childbearing potential who do not want adequate contraception Patients with a diagnosis of prior malignancy unless disease-free for at least 5 years following therapy with curative intent (except curatively treated nonmelanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia)

Ages Eligible for Study
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Minimum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PTCy<br>Patients who receive post-transplantation cyclophosphamide | Drug: Cyclophosphamide<br>* Cyclophosphamide 50 mg/kg/day i.v. daily on days 3 and 4 of hematopoietic cell transplantation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the incidence of acute and chronic graft-versus-host disease |  | 100 days and 2 year, respectively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDS, AML progressed from MDS, CMML