Bone Marrow Failure Syndromes, Immune Dysregulation Syndromes, Immunodeficiencies
Conditions
Keywords
Transplant related mortality, Graft versus host disease, Bone marrow transplant
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.
Interventions
DEVICECliniMACs device
Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
Sponsors
Children's Hospital of Philadelphia
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells.
Eligibility
Sex/Gender
ALL
Age
No minimum to 22 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Engraftment | One Year | The primary objective is to determine event free survival with durable stable engraftment of donor cells at one year. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bone Marrow Failure Syndrome Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion.
CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. | 0 |
| Immunodeficiency / Dysregulation Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. Reduced intensity conditioning will include Busulfan, Fludarbine, Cyclophosphamide followed by stem cell infusion.
CD3+/CD19+ delpletion using CliniMACs device follwing reduced intensity conditioning: Reduced intensity conditioning with chemotherapy followed by stem cell transplant using the CliniMACs device to deplete CD3+ CD19+ peripheral stem cells. | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Immunodeficiency / Dysregulation | Total |
|---|---|---|
| Age, Continuous | 9.5 years | 9.5 years |
| Sex: Female, Male Female | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 2 |
| other Total, other adverse events | 0 / 0 | 0 / 2 |
| serious Total, serious adverse events | 0 / 0 | 0 / 2 |
Outcome results
Primary
Number of Participants With Engraftment
The primary objective is to determine event free survival with durable stable engraftment of donor cells at one year.
Time frame: One Year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Immunodeficiency / Dysregulation | Number of Participants With Engraftment | 2 Participants |