HCT With PTCy in Higher-risk MDS

Study Overview
=================
Brief Summary
-----------------
This study is conducted to evaluate the efficacy of post-transplantation cyclophosphamide with myeloablative or reduced-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with higher-risk myelodysplastic syndrome (MDS). The efficacy of the treatment will be measured in terms of the GVHD-free, relapse-free survival. The secondary end points of the study include engraftment, relapse incidence, non-relapse mortality, graft-versus-host disease, donor chimerism, immune reconstitution, infections, and survivals (overall and event-free).

Detailed Description
-----------------
This study is conducted to evaluate the efficacy of post-transplantation cyclophosphamide with myeloablative or reduced-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with higher-risk myelodysplastic syndrome (MDS). The efficacy of the treatment will be measured in terms of the GVHD-free, relapse-free survival. The secondary end points of the study include engraftment, relapse incidence, non-relapse mortality, graft-versus-host disease, donor chimerism, immune reconstitution, infections, and survivals (overall and event-free).

Official Title
-----------------
Efficacy and Safety of Allogeneic Hematopoietic Cell Transplantation Using Post-transplantation Cyclophosphamide for Graft-versus-host Disease Prophylaxis in Higher-risk Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, and Secondary AML Patients

Conditions
-----------------
Patients With MDS, Acute Myeloid Leukemia (AML) Evolving From MDS, and Chronic Myelomonocytic Leukemia (CMML)

Intervention / Treatment
-----------------
* Drug: Cyclophosphamide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: MDS defined by WHO classification, CMML, or AML evolving from MDS A. International Prognostic Scoring System (IPSS) > 1.0 or bone marrow blast ≥ 5% at any time points before HCT or B. AML progressed from MDS or C. CMML with bone marrow blast ≥ 5% at any time points before HCT 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 , under 75 years Adequate performance status (Karnofsky score of 70 or more) Adequate hepatic function (AST or ALT < 3 x upper normal limits and bilirubin < 1.5 x upper normal limit). Adequate renal function (creatinine < 2.0 mg/dL or creatinine clearance ≥ 50 mL/min) Adequate cardiac function (left ventricular ejection fraction ≥ 50% on heart scan or echocardiogram) Adequate pulmonary function: DLCO, FEV1, and FVC ≥ 45% predicted by pulmonary function tests 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) Presence of contraindications to cyclophosphamide (patients receiving pentostatin, symptomatic cystitis, urinary tract obstruction, with a history of hypersensitivity reactions to the component of the drug)

Ages Eligible for Study
-----------------
Minimum Age: 15 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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 (for 2 days)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GVHD-free, relapse-free survival | This study is conducted to evaluate the efficacy of post-transplantation cyclophosphamide with myeloablative or reduced-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with higher-risk myelodysplastic syndrome (MDS). The efficacy of the treatment will be measured in terms of the GVHD-free, relapse-free survival. | 8 years |