Reduced Intensity Conditioning Using CD3+/CD19+ Depletion for Non Malignant Transplantable Diseases (MiniClini)

Children's Hospital of Philadelphia (CHOP)

Status and phase: Completed; Phase 2

Conditions: Immune Dysregulation Syndromes; Bone Marrow Failure Syndromes; Immunodeficiencies

Treatments: Device: CliniMACs device

Study type: Interventional

Funder types: Other

Identifiers

NCT02277639

CHP 980 (Other Identifier)

11-008330

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2 patients

Sex: All

Ages: Under 22 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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2 participants in 2 patient groups

Bone Marrow Failure Syndrome

Experimental group

Description:

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.

Treatment:

Device: CliniMACs device

Immunodeficiency / Dysregulation

Experimental group

Description:

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.

Treatment:

Device: CliniMACs device