Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases
| Status: | Completed |
|---|---|
| Conditions: | Infectious Disease, HIV / AIDS, Hematology, Hematology |
| Therapuetic Areas: | Hematology, Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | Any - 22 |
| Updated: | 4/17/2018 |
| Start Date: | November 2011 |
| End Date: | March 2016 |
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
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.
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.
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.
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.
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
We found this trial at
1
site
South 34th Street
Philadelphia, Pennsylvania 19104
Philadelphia, Pennsylvania 19104
215-590-1000
Principal Investigator: Nancy Bunin, MD
Phone: 215-590-4019
Children's Hospital of Philadelphia Since its start in 1855 as the nation's first hospital devoted...
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