HCT With PTCy in Higher-risk MDS

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Patients With MDS, Acute Myeloid Leukemia (AML) Evolving From MDS, and Chronic Myelomonocytic Leukemia (CMML)
• Intervention / Treatment: Drug: Cyclophosphamide

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).

• Study Type: Interventional
• Enrollment (Estimated): 113
• 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: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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)

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 (for 2 days)

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

Collaborators and Investigators

• Sponsor: Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027

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 by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid; Chronic Disease; Leukemia; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; 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: HRMDS_PTCy_2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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