GVH - Graft Versus Host Reaction, Transplant-Related Disorder
Conditions
Keywords
TCR Alpha/Beta, CliniMACS
Brief summary
The protocol is designed to provide access to patients to the Clinimacs® CD34 TCRαβ system to prepare cells for an unlabeled indication using an HLA-compatible related or unrelated donor for allogenic transplant.
Detailed description
Allogeneic hematopoietic stem cell transplant (HSCT) is the only known curative therapy for a variety of non-malignant and malignant disorders1-4. Only about 25% of patients have an HLA-matched sibling and in about 16-75% (depending on ethnicity), a 10/10 HLA-matched unrelated donor can be identified. Engraftment failure is a dynamic complex process that may occur with this product due to unbalanced depletion of T-cells between recipient and donor, not only due to low number of CD34 cells. The use of mis-matched or haploidentical donors is associated with a higher risk of post-transplant mortality due to the development of severe graft versus host disease, graft failure and the development of infection due to the use of immunosuppression or T cell depletion. A total of 10 patients will be enrolled. The patients will be divided into 2 strata (haploidentical 7, unrelated donor 3).
Interventions
DEVICECliniMACS® CD34 TCR Alpha/Beta
CliniMACS System uses an automated antibody/magnetic beads column system that allows efficient depletion of TCRαβ and CD19+ cells without relevant loss of cell viability. Hematopoietic stem cells are retained in sufficient numbers to permit engraftment and hematopoietic reconstitution. Humanitarian Exemption IDE approval has been obtained for CD34+ cell selection as a method of T-cell depletion.
Sponsors
Victor Aquino
Eligibility
Sex/Gender
ALL
Age
No minimum to 21 Years
Healthy volunteers
No
Inclusion criteria
Recipient Inclusion Criteria: * Age less than 22 years of age * No available genotypically matched related donor (sibling) * Availability of a suitable donor and graft source * Haploidentical related mobilized peripheral blood cells * 9/10 or 10/10 allele matched (HLA-A, -B, -C, -DRB1, -DQB1) volunteer unrelated donor mobilized peripheral blood cells Donor Inclusion Criteria: * Matching as described in the Recipient and Donor Suitability Criteria * Size and vascular access appropriate by center standard for peripheral blood stem cell (PBSC) collection. Donors with inadequate peripheral access will require placement of an apheresis catheter for collection. * Must meet appropriate screening/eligibility requirements: * Haploidentical matched family members: screened by center health screens and found to be eligible. * Unrelated donors: meet suitability criteria to donate PBSC * HIV negative * Not pregnant or lactating * Recipient must not have high-level donor specific anti-HLA antibodies according to institutional practices. * Must agree to donate PBSC * Must give informed consent Recipient Suitability: \- Adequate organ functioning as demonstrated by: * MUGA ≥ 50% or ECHO >30% * 24-hour Creatinine Clearance or Glofil ≥ 50 ml/min or Serum Creatinine ≤2 times the upper limit of normal * DLCO > 65% of predicted value. FEV1 >65% of predicted * AST / ALT ≤ 2.5 and/or Bilirubin ≤ 1.5 times the upper limit of normal * Pregnancy test negative * HIV 1 / 2 (HIV screen) negative with a negative qualitative HIV PCR. * HTLV I negative * RPR or VDRL negative * RVP (Respiratory Viral PCR) with a negative result * Positive hepatitis testing does not make the patient ineligible. Hepatitis results will be evaluated on a case-by-case basis by the transplant physician to determine donor suitability/eligibility. Donor Suitability: \- Allowed Donor Sources * Fully matched sibling donors are not allowed. * Unrelated donors. HLA typing of at least 10 alleles is required. Donor must be matched at 9/10 or 10/10 alleles (HLA-A, -B, -C, -DRB1, -DQB1). Haploidentical matched family members. Minimum match level full haploidentical (at least 5/10; HLA-A, -B, -C, -DRB1, -DQB1 alleles), but use of haploidentical donors with extra matches (e.g., 6, 7, or 8/10) encouraged. * Cord blood is not allowed as a stem cell source on this IDE. Recipient and Donor
Exclusion criteria
* Pregnant or lactating females are ineligible as the risk to unborn children and infants is unknown * Presence of life-threatening, uncontrolled opportunistic infection (fungal, bacterial, or viral infections). Patients with history of fungal disease during induction therapy may proceed if they have a significant response to antifungal therapy with no or minimal evidence of disease remaining by CT evaluation. * HIV or HTLV I/II infection
Countries
United States
Contacts
Primary ContactVictor Aquino, MD
Outcome results
None listed