The protocol is designed to provide access to patients to the Clinimacs® CD34 TCRαβsystem to prepare cells for an unlabeled indication using an HLA-compatible related orunrelated donor for allogenic transplant.
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).
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 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
Children's Medical Center - Dallas
Dallas, Texas, United States
Investigator: Victor Aquino, MD
Contact: 214-456-2382
Victor.Aquino@utsouthwestern.edu
Victor Aquino, MD
214-648-3896
Victor.Aquino@utsouthwestern.edu
Not Provided