Pediatric Study of GVHD Ppx w/o Calcineurin Inhibitors After Day60 Post First Allo HSCT for Hematological Malignancies.

Phase 2

Terminated

• Conditions: Myeloid Malignancy; Hematologic Malignancy
• Interventions: Drug: Ruxolitinib; Drug: Mesna; Drug: Anti-thymocyte globulin (ATG); Drug: Cyclosporine; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Methotrexate; Radiation: Total Body Irradiation (radiation treatment); Drug: Bone marrow infusion; Drug: Busulfan; Drug: Thiotepa

• Registration Number: NCT05579769
• Lead Sponsor: St. Jude Children's Research Hospital

Brief Summary

The participants are being asked to take part in this clinical trial because the participant have a lymphoid or myeloid based cancer diagnosis that requires a bone marrow transplant.

Primary Objectives

To estimate the incidence of severe acute GVHD (saGVHD) using a prophylaxis regimen with no calcineurin inhibitors after day +60 post first allogeneic Human Leukocyte antigen (HLA)-matched sibling or unrelated donor HCT for hematological malignancies.

Secondary objective

Determine the cumulative incidence of relapse, NRM, chronic GVHD, and OS in study participants at one year post-transplant.

Exploratory objectives

* To evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of ruxolitinib, fludarabine, and rATG.

* To assess immune reconstitution in study participants within the first year post-HCT.

Detailed Description

The investigator propose to employ two preparative regimens based on the underlying hematological malignancy. For hematological malignancies of the lymphoid lineage we will use a standard preparative regimen consisting of Total Body Irradiation and cyclophosphamide (TBI/Cy), unless TBI is contraindicated. For myeloid malignancies we will use thiotepa, busulfan, and fludarabine (TBF), a preparative regimen that has been associated with a reduced risk of relapse and trend for improved survival with comparable NRM in comparison to busulfan and cyclophosphamide (BuCy), our current regimen. All HCT recipients will receive cyclosporine in combination with methotrexate and ruxolitinib as GVHD prophylaxis. Recipients of MUD HCT will receive rATG for additional immunosuppression as is standard for unrelated donor transplants

Study Timeline

• Study First Submitted: 2022-10-11
• Study First Submitted QC: 2022-10-11
• Study First Posted: 2022-10-14
• Study Start: 2023-03-14
• Primary Completion: 2024-05-08
• Study Completion: 2024-05-08
• Results First Submitted: 2025-03-11
• Status Verified: 2025-09
• Results First Submitted QC: 2025-09-12
• Last Update Submitted: 2025-09-12
• Results First Posted: 2025-10-02
• Last Update Posted: 2025-10-02

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Transplant Patients	Ruxolitinib	-
Transplant Patients	Mesna	-
Transplant Patients	Anti-thymocyte globulin (ATG)	-
Transplant Patients	Cyclosporine	-
Transplant Patients	Cyclophosphamide	-
Transplant Patients	Fludarabine	-
Transplant Patients	Methotrexate	-
Transplant Patients	Total Body Irradiation (radiation treatment)	-
Transplant Patients	Bone marrow infusion	-
Transplant Patients	Busulfan	-
Transplant Patients	Thiotepa	-

Primary Outcome Measures

Name	Time	Method
Proportion of saGVHD Using a ProphylaxisRegimen With no Calcineurin Inhibitors After Day 100 Post First Allogeneic HLA-Matched Sibling or Unrelated Donor HCT for Hematological Malignancies.	100 days post transplant	Development of Severe Acute GVHD (saGVHD) at or before Day 100 post transplant is considered as an event. Severe acute GVHD is defined as grade II-IVGVHD. Acute graft-vs-host disease will be evaluated using the standard grading criteria.

Secondary Outcome Measures

Name	Time	Method
Cumulative Incidence of Overall Survival (OS)	One-year post-transplantation.	The one-year survival is defined by the participant who has not died within one year after post transplantation. The rate is calculated by computing the ratio between total number of one year survival patients and the total number of patients.
Cumulative Incidence of Relapse	One-year post-transplantation.	Bone marrow studies for disease status evaluation will be performed at 1-year post-transplant. Testing will include a research evaluation for minimal residual disease.
Cumulative Incidence of Non Relapse Mortality (NRM)	One-year post-transplantation.	Non-relapse mortality is death without evidence of disease relapse or progression. The rate is calculated by computing the ratio between total number of NRM patients and the total number of patients.
Cumulative Incidence of Chronic GVHD	One-year post-transplantation.	Chronic graft-vs-host disease will be evaluated using the standard grading criteria.

Trial Locations

Locations (1)

St. Jude Children's Research Hospital; 🇺🇸 Memphis, Tennessee, United States