CyFluATG in Lower Risk MDS

Study Overview
=================
Brief Summary
-----------------
To evaluate the efficacy of the conditioning regimen with cyclophosphamide, fludarabine, and antithymocyte globulin (CyFluATG) for allogeneic hematopoietic cell transplantation (HCT) in patients with lower risk myelodysplastic syndrome (MDS). The efficacy of the treatment will be measured in terms of engraftment and non-relapse mortality (NRM).

Detailed Description
-----------------
This is a prospective, phase 2 extension study Conditioning regimen A. Cyclophosphamide 50 mg/kg/day i.v. daily on days -3 and -2 (for 2 days) B. Fludarabine 30 mg/m2/day i.v. daily on days -7to -2 (for 6 days) C. Antithymocyte globulin (Thymoglobulin) 1.5 mg/kg/day (for HLA-matched sibling donor HCT) or 3.0 mg/kg/day (for other alternative donor HCT) i.v. daily on days -3 to -1 (for 3 days) D. Methylprednisolone 2 mg/kg i.v. daily on days -4 to -1 (for 4 days) Harvest and infusion of donor hematopoietic cells A. 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. Cyclosporine: 1.5 mg/kg i.v. every 12 hours beginning on day -1 and changed to oral dosing (with twice the i.v. dose) when oral intake is possible. B. Methotrexate: 15 mg/m2 i.v. on day 1, and 10 mg/m2 i.v. on days 3 and 6.

Official Title
-----------------
Allogeneic Hematopoietic Cell Transplantation With Cyclophosphamide, Fludarabine, and Antithymocyte Globulin in Lower Risk Myelodysplastic Syndrome Phase 2 Extension Study

Conditions
-----------------
Myelodysplastic Syndromes

Intervention / Treatment
-----------------
* Drug: cyclophosphamide, fludarabine, and antithymocyte globulin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with lower risk MDS A. International prognosticscoring system (IPSS) ≤ 1.0 and B. Bone marrow blast percentage < 5% during the disease course before HCT Patients with appropriate hematopoietic cell donor A. HLA-matched sibling B. HLA-matched unrelated donor C. HLA-mismatched familial donor 18 years old or older, 70 years old or younger 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
-----------------
Minimum Age: 18 Years
Maximum Age: 70 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: CyFluATG<br>Patients who receive with cyclophosphamide, fludarabine, and antithymocyte globulin (CyFluATG) for allogeneic hematopoietic cell transplantation | Drug: cyclophosphamide, fludarabine, and antithymocyte globulin<br>* Cyclophosphamide 50 mg/kg/day i.v. daily on days -3 and -2 (for 2 days) Fludarabine 30 mg/m2/day i.v. daily on days -7to -2 (for 6 days) Antithymocyte globulin (Thymoglobulin) 1.5 mg/kg/day (for HLA-matched sibling donor HCT) or 3.0 mg/kg/day (for other alternative donor HCT) i.v. daily on days -3 to -1 (for 3 days)<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| engraftment and non-relapse mortality | To evaluate the efficacy of the conditioning regimen with cyclophosphamide, fludarabine, and antithymocyte globulin (CyFluATG) for allogeneic hematopoietic cell transplantation (HCT) in patients with lower risk myelodysplastic syndrome (MDS). The efficacy of the treatment will be measured in terms of engraftment and non-relapse mortality (NRM). | 8 years |