Hematopoietic Cell Transplantation With Post-transplantation Cyclophosphamide in MDS

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

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).

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Cyclophosphamide

Detailed Description

• 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.

• Study Type: Interventional
• Enrollment (Actual): 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: 15 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

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: PTCy; Patients who receive post-transplantation cyclophosphamide	Drug: Cyclophosphamide; Cyclophosphamide 50 mg/kg/day i.v. daily on days 3 and 4 of hematopoietic cell transplantation

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Asan Medical Center

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Actual): December 16, 2021
• Study Completion (Actual): December 16, 2021

Study Registration Dates

• First Submitted: November 17, 2016
• First Submitted That Met QC Criteria: November 17, 2016
• First Posted (Estimated): November 21, 2016

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: MDS; CMML; AML progressed from MDS
• 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
• Other Study ID Numbers: MDS_PTCy_2016