A Phase II Pediatric Study of a Graft-VS.-Host Disease (GVHD) Prophylaxis Regimen With no Calcineurin Inhibitors After Day +60 Post First Allogeneic Hematopoietic Cell Transplant for Hematological Malignancies
- Conditions
- Myeloid MalignancyHematologic Malignancy
- Interventions
- Drug: Anti-thymocyte globulin (ATG)Radiation: Total Body Irradiation (radiation treatment)Drug: Bone marrow infusion
- 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
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 3
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ArmA- Lymphoid Bone marrow infusion Total Body Irradiation and cyclophosphamide (TBI/Cy) ArmB-Myeloid Anti-thymocyte globulin (ATG) TBF with comparable NRM in comparison to busulfan and cyclophosphamide (BuCy) ArmA- Lymphoid Total Body Irradiation (radiation treatment) Total Body Irradiation and cyclophosphamide (TBI/Cy) ArmA- Lymphoid Ruxolitinib Total Body Irradiation and cyclophosphamide (TBI/Cy) ArmA- Lymphoid Anti-thymocyte globulin (ATG) Total Body Irradiation and cyclophosphamide (TBI/Cy) ArmB-Myeloid Ruxolitinib TBF with comparable NRM in comparison to busulfan and cyclophosphamide (BuCy) ArmB-Myeloid Bone marrow infusion TBF with comparable NRM in comparison to busulfan and cyclophosphamide (BuCy) ArmA- Lymphoid Mesna Total Body Irradiation and cyclophosphamide (TBI/Cy) ArmA- Lymphoid Cyclosporine Total Body Irradiation and cyclophosphamide (TBI/Cy) ArmA- Lymphoid Cyclophosphamide Total Body Irradiation and cyclophosphamide (TBI/Cy) ArmA- Lymphoid Methotrexate Total Body Irradiation and cyclophosphamide (TBI/Cy) ArmB-Myeloid Cyclosporine TBF with comparable NRM in comparison to busulfan and cyclophosphamide (BuCy) ArmB-Myeloid Fludarabine TBF with comparable NRM in comparison to busulfan and cyclophosphamide (BuCy) ArmB-Myeloid Methotrexate TBF with comparable NRM in comparison to busulfan and cyclophosphamide (BuCy) ArmB-Myeloid Busulfan TBF with comparable NRM in comparison to busulfan and cyclophosphamide (BuCy) ArmB-Myeloid Thiotepa TBF with comparable NRM in comparison to busulfan and cyclophosphamide (BuCy)
- Primary Outcome Measures
Name Time Method Proportion of severe acute GVHD (saGVHD) using a prophylaxis regimen with no calcineurin inhibitors after day 100 post first allogeneic Human Leukocyte antigen (HLA)-matched sibling or unrelated donor HCT for hematological malignancies. 100 days post transplant Development of saGVHD at or before Day 100 post transplant is considered as an event.
- Secondary Outcome Measures
Name Time Method Incidence of Leukemic Relapse One-year post-transplantation. Bone marrow studies for disease status evaluation will be performed.
Non-relapse mortality One-year post-transplantation The one-year non-relapse mortality (NRM is defined by the patient who expire while in remission within one year. The probability of NRM is estimated by the cumulative incidence method.
Overall Survival one year post-transplantation The one-year survival is defined by the patient who has not died within one year after post transplantation. The probability is estimated by the Kaplan-Meier method.
Incidence of Chronic Graft Versus Host Disease (cGVHD) 1 year post transplant Ongoing assessment of toxicity will be done using the NCI CTCAE version 3.0. Acute and chronic graft-vs.-host disease will be evaluated using the standard grading criteria. The cumulative incidence of cGvHD will be estimated using Kalbfleisch-Prentice method.
Trial Locations
- Locations (1)
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States