Clinical Trial: Reduced Intensity Conditioning in Patients Aged ≤35 With Non-Malignant Disorders Undergoing UCBT, BMT, or PBSCT

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase II Study of Reduced Intensity Conditioning in Patients ≤35 Years of Age With Non-Malignant Disorders Undergoing Umbilical Cord Blood, Bone Marrow, or Peripheral Blood Stem Cell Transplan

Brief Summary: The objective of this study is to demonstrate the efficacy of using a reduced-intensity condition regimen with 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 HSCT. After transplant, subjects will be followed for late effects and for ongoing graft success.

Detailed Summary:

Hematopoietic stem cell transplantation (HSCT) is the only curative therapy for many pediatric malignant and non-malignant disorders (NMD), the latter of which includes primary immunodeficiencies (PID), hemoglobinopathies, inherited metabolic disorders, and bone marrow failure syndromes. These NMD often have significant morbidity and risk for premature mortality, and HSCT can be curative by either replacement of defective hematopoietic cells with healthy donor cells or by the production of deficient enzyme by donor cells. HSCT in patients with NMD differs from that in malignant disorders for two important reasons- first, that these patients are typically naïve to chemotherapy and immunosuppression potentially leading to difficulties with engraftment, and second, that in the absence of malignancy, reduced-intensity conditioning (RIC) with subsequent bone marrow chimerism may be curative and result in decreased transplant-related mortality (TRM).

In this research study, instead of using the standard myeloablative conditioning, the study doctor is using reduced-intensity conditioning (RIC), in which lower doses of chemotherapy will be used. Although the lower doses may not eradicate every single stem cell in the bone marrow, nevertheless in the presented combination it still intends to eliminate already formed immune cells, paving the way to successful engraftment of donor cord blood cells. Engrafting cord blood cells can outcompete and reject the patients' few surviving stem cells. With reduced-intensity conditioning, the side effects on brain, heart, lung, liver, and other organ functions are usually less severe, and the patients can have a better long-term recovery. There is also realistic hope that after lower doses of chemotherapy many patients will avoid becoming sterile.

The purpose of this study is to collect dat
Sponsor: University of Pittsburgh

Current Primary Outcome:

• Post-transplant treatment-related mortality (TRM) [ Time Frame: 1 year post-transplant ]
  Assessment of post-transplant treatment-related mortality at day 100, day 180, and 1 year
• Neurodevelopmental milestones [ Time Frame: 2 years 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
• Immune Reconstitution [ Time Frame: 2 years post-transplant ]
  Evaluation of the pace of immune reconstitution
• Severe opportunistic infections [ Time Frame: 2 years post-transplant ]
  Evaluation of the incidence of severe opportunistic infections
• GVHD occurrence [ Time Frame: 2 years post-transplant ]
  Description of the incidence of acute GVHD (II-IV) and chronic extensive GVHD

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Donor cell engraftment [ Time Frame: 180 days post-transplant ]
  Determination of the feasibility of attaining robust donor cell engraftment (>50% donor chimerism at 180 days) following reduced-intensity conditioning (RIC) regimens prior to HSCT in the target population
• Normal enzyme level [ Time Frame: 2 years post-transplant ]
  Determination of the feasibility of attaining and sustaining normal enzyme levels in the target population
• Neutrophil recovery [ Time Frame: 2 years post-transplant ]
  Determination of the pace of neutrophil recovery
• Platelet recovery [ Time Frame: 2 years post-transplant ]
  Determination of the pace of platelet recovery
• Grade 3-4 organ toxicity [ Time Frame: 2 years post-transplant ]
  Description of the incidence of grade 3-4 organ toxicity
• Long-term complications [ Time Frame: 2 years post-transplant ]
  Evaluation of the long-term complications such as sterility, endocrinopathy, and growth failure
• Late graft failure [ Time Frame: 2 years post-transplant ]
  Evaluation of the incidence of late graft failure

Original Secondary Outcome:

• Donor cell engraftment [ Time Frame: 180 days post-transplant ]
  Determination of the feasibility of attaining robust donor cell engraftment (>50% donor chimerism at 180 days) following reduced-intensity conditioning (RIC) regimens prior to UCBT in the target population
• Normal enzyme level [ Time Frame: 2 years post-transplant ]
  Determination of the feasibility of attaining and sustaining normal enzyme levels in the target population
• Neutrophil recovery [ Time Frame: 2 years post-transplant ]
  Determination of the pace of neutrophil recovery
• Platelet recovery [ Time Frame: 2 years post-transplant ]
  Determination of the pace of platelet recovery
• Grade 3-4 organ toxicity [ Time Frame: 2 years post-transplant ]
  Description of the incidence of grade 3-4 organ toxicity
• Long-term complications [ Time Frame: 2 years post-transplant ]
  Evaluation of the long-term complications such as sterility, endocrinopathy, and growth failure
• Late graft failure [ Time Frame: 2 years post-transplant ]
  Evaluation of the incidence of late graft failure

Information By: University of Pittsburgh

Dates:
Date Received: October 10, 2013
Date Started: December 2013
Date Completion: November 2019
Last Updated: March 16, 2017
Last Verified: March 2017