Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT
- Conditions
- Primary Immunodeficiency (PID)Inherited Metabolic Disorders (IMD)Congenital Bone Marrow Failure SyndromesHereditary AnemiasJuvenile Rheumatoid Arthritis (JRA)Inflammatory ConditionsSystemic Juvenile Idiopathic Arthritis (sJIA)
- Interventions
- Registration Number
- NCT01962415
- Lead Sponsor
- Paul Szabolcs
- Brief Summary
The objective of this study is to evaluate the efficacy of using a reduced-intensity condition (RIC) regimen with umbilical cord blood transplant (UCBT), double cord UCBT, matched unrelated donor (MUD) bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) in patients with non-malignant disorders that are amenable to treatment with hematopoietic stem cell transplant (HSCT). After transplant, subjects will be followed for late effects and for ongoing graft success.
- Detailed Description
For some non-malignant diseases (NMD; i.e., thalassemia, sickle cell disease, most immune deficiencies) a hematopoietic stem cell transplant may be curative by healthy donor stem cell engraftment alone. HSCT in patients with NMD differs from that in malignant disorders for two important reasons: 1) these patients are typically naïve to chemotherapy and immunosuppression. This may potentially lead to difficulties with engraftment. And 2) RIC with subsequent bone marrow chimerism may be beneficial even in mixed chimerism and result in decreased transplant-related mortality (TRM). Nevertheless, any previous organ damage, as a result of the underlying disease, may remain present after the HSCT.
For other diseases (metabolic disorders, some immunodeficiencies, etc.), a transplant is not curative. For these diseases, the main intent of the transplant is to slow down, or stop, the progress of the disease. In select few cases/diseases, the presence of healthy bone marrow derived cells may even prevent progression and prevent neurological decline.
Research funds are not available to assist with enrollment on this trial.
In this research study, instead of using the standard myeloablative conditioning, the study doctor is using RIC, in which significantly lower doses of chemotherapy will be used. The lower doses may not eradicate every stem cell in the patient's bone marrow, however, in the presented combination, the intention is to eliminate already formed immune cells and provide maximum growth advantage to healthy donor stem cells. This paves the way to successful engraftment of donor stem cells. Engrafting donor stem cells can outcompete, and donor lymphocytes could suppress, the patients' surviving stem cells. With RIC, the side effects on the brain, heart, lung, liver, and other organ functions are less severe and late toxic effects should also be reduced.
The purpose of this study is to collect data from the patients undergoing reduced-intensity conditioning before HSCT, and compare it to the standard myeloablative conditioning. It is expected there will be therapeutic benefits, paired with better survival rate, less organ toxicity and improved quality of life, following the RIC compared to the myeloablative regimen.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 100
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description UCBT:transfusion dependent anemias or increased rejection risk Hydroxyurea Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT. UCBT:transfusion dependent anemias or increased rejection risk Alemtuzumab Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT. UCBT:transfusion dependent anemias or increased rejection risk Fludarabine Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT. UCBT:transfusion dependent anemias or increased rejection risk Melphalan Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT. UCBT:transfusion dependent anemias or increased rejection risk Thiotepa Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT. BMT, PBSCT and not transfusion dependent UCBT Thiotepa Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT. BMT, PBSCT and not transfusion dependent UCBT Hydroxyurea Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT. BMT, PBSCT and not transfusion dependent UCBT Alemtuzumab Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT. BMT, PBSCT and not transfusion dependent UCBT Fludarabine Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT. BMT, PBSCT and not transfusion dependent UCBT Melphalan Alemtuzumab, Hydroxyurea, Fludarabine, Melphalan, and Thiotepa conditioning regimen prior to allogenic HSCT.
- Primary Outcome Measures
Name Time Method Post-transplant treatment-related mortality (TRM) 1 year post-transplant The number of deaths related to the research intervention at day 100, 6 months, and 1 year post-transplant.
GVHD occurrence 1 year post-transplant Description of the incidence of acute graft versus host disease (GVHD) (II-IV) and chronic extensive GVHD.
Immune Reconstitution 1 year post-transplant Evaluation of the pace of immune reconstitution.
Severe opportunistic infections 1 year post-transplant Evaluation of the incidence of severe opportunistic infections.
Neurodevelopmental milestones 1 year post-transplant Evaluation of the pace of attaining neurodevelopmental milestones after reduced-intensity conditioning as compared to myeloablative conditioning historical controls from the target population(s).
- Secondary Outcome Measures
Name Time Method Neutrophil recovery 1 year post-transplant Determination of the pace of neutrophil recovery.
Late graft failure 1 year post-transplant Evaluation of the incidence of late graft failure.
Donor cell engraftment 6 months post-transplant Determination of the feasibility of attaining robust donor cell engraftment (\>50% donor chimerism at 6 months) following reduced-intensity conditioning (RIC) regimens prior to HSCT in the target population(s).
Normal enzyme level 1 year post-transplant Determination of the feasibility of attaining and sustaining normal enzyme levels in the target population(s).
Grade 3-4 organ toxicity 1 year post-transplant The number of grade 3-4 organ adverse events.
Platelet recovery 1 year post-transplant Determination of the pace of platelet recovery.
Trial Locations
- Locations (1)
UPMC Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States