Phase I/II Study of Reduced Intensity Conditioning for Patients With Non-Malignant Diseases Using CD3+/CD19+ Depleted Unrelated Donor or Partially Matched Related Donor Peripheral Stem Cells
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Bone Marrow Failure Syndromes
- Sponsor
- Children's Hospital of Philadelphia
- Enrollment
- 2
- Locations
- 1
- Primary Endpoint
- Number of Participants With Engraftment
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This is a Phase II trial to determine the ability of a reduced intensity conditioning regimen to allow successful engraftment with CD3+ /CD19+ depleted peripheral stem cell grafts from mismatched donors. There are two conditioning regimens depending upon patient diagnosis and age.
Detailed Description
This study will allow transplantation using a reduced intensity conditioning regimen for children with non-malignant diseases who lack a matched related or unrelated donor. Donors will be unrelated or partially matched related, depending upon urgency and availability. If each parent is haploidentical, the mother will be preferred, as there is evidence of reduced transplant related mortality and superior survival with a maternal donor. The risks of severe graft vs host disease (GVHD) and Epstein-Barr lymphoproliferative disorder will be reduced or eliminated by T and B cell depletion using the Miltenyi Clinimacs device. Patients with bone marrow failure syndromes, who are at high risk for rejection, will undergo pre-conditioning immune suppression with Thymoglobulin. It is recommended that patients with immunedysregulation syndromes receive pre-RIC alemtuzumab as this may reduce the risk on non-engraftment and hyperinflammatory states. Post-transplant immune suppression will be used to prevent GVHD, as CD3 depletion does not deplete as completely as CD34+ selection. It will be rapidly weaned if no GVHD by day 100 to allow immune reconstitution.
Investigators
Nancy Bunin
BMT Medical Director
Children's Hospital of Philadelphia
Eligibility Criteria
Inclusion Criteria
- •Bone marrow failure syndromes for which SCT is indicated, including severe aplastic anemia refractory to non transplant therapies congenital neutropenia, congenital thrombocytopenia, congenital red cell aplasia
- •Immunodeficiencies for which allogeneic hematopoietic stem cell transplant is indicated, including severe combined immunodeficiencies, Wiskott-Aldrich syndrome, IPEX syndrome, X-linked lymphoproliferative disease
- •Immune dysregulation syndromes, including refractory or recurrent hemophagocytic lymphohistiocytosis, HLH with genetic mutations, refractory multisystemic Langerhans cell histiocytosis, other MAS refractory to standard therapy
- •Organ function clearance
Exclusion Criteria
- •Uncontrolled bacterial, viral or fungal infections
- •HLA matched related or unrelated donor able to donate mobilized peripheral stem cells.
- •Fanconi's syndrome, dyskeratosis congenita or other chromosomal fragility syndromes
- •Pregnant Females
Outcomes
Primary Outcomes
Number of Participants With Engraftment
Time Frame: One Year
The primary objective is to determine event free survival with durable stable engraftment of donor cells at one year.