CyFluATG in Lower Risk MDS

Sponsor

Asan Medical Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT06098326

Collaborator

(none)

Enrollment

Location

Arm

105.9

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Drug: cyclophosphamide, fludarabine, and antithymocyte globulin	Phase 2

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.

Methotrexate: 15 mg/m2 i.v. on day 1, and 10 mg/m2 i.v. on days 3 and 6.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 6, 2018

Anticipated Primary Completion Date :

Dec 31, 2026

Anticipated Study Completion Date :

Dec 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CyFluATG Patients who receive with cyclophosphamide, fludarabine, and antithymocyte globulin (CyFluATG) for allogeneic hematopoietic cell transplantation	Drug: cyclophosphamide, fludarabine, and antithymocyte globulin 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)

Arm

Intervention/Treatment

Experimental: CyFluATG

Patients who receive with cyclophosphamide, fludarabine, and antithymocyte globulin (CyFluATG) for allogeneic hematopoietic cell transplantation

Drug: cyclophosphamide, fludarabine, and antithymocyte globulin

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)

Outcome Measures

Primary Outcome Measures

engraftment and non-relapse mortality [8 years]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)