CyFluATG in Lower Risk MDS

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: cyclophosphamide, fludarabine, and antithymocyte globulin

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center, University of Ulsan College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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)

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

Collaborators and Investigators

• Sponsor: Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2018
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: October 19, 2023
• First Submitted That Met QC Criteria: October 19, 2023
• First Posted (Actual): October 24, 2023

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine; Antilymphocyte Serum
• Other Study ID Numbers: LRMDS_CyFluATG_2018

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No