The purpose of this IDE protocol is to provide access to TCR Alpha/Beta+/CD19+ depleted allogeneic hematopoietic stem cell (HSC) in patients who require hematopoietic stem cell transplantation.
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. 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. The protocol is designed to provide access to patients
to the Clinimacs® CD34 TCR Alpha/Beta system to prepare cells for an unlabeled indication
using an HLA-compatible related or unrelated donor for allogenic transplant.
Device: CliniMACS® 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.
Recipient Inclusion Criteria:
- Age less than 18 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
Children's Medical Center - Dallas
Dallas, Texas, United States
Not Provided