Haploidentical Hematopoietic Stem Cell Transplantation With Ex Vivo TCR Alpha/Beta and CD19 Depletion in Pediatric Hematologic Malignancies
Pediatric Hematologic Malignancies
About this trial
This is an interventional treatment trial for Pediatric Hematologic Malignancies
Eligibility Criteria
Recipient Inclusion Criteria:
Must meet at least one of the following disease criteria:
ALL in CR (defined by < 5% blasts in adequate bone marrow specimen) AND at least one of the following:
- Induction failure
- Relapsed or refractory disease
AML in CR (defined by < 5% blasts on an adequate bone marrow specimen) with one of the following high-risk cytogenetic features:
- High allelic FLT3/ITD ratio
- Monosomy 7
- Monosomy 5 or Del(5q)
- Relapsed or refractory disease
- Any acute leukemia in CR ≥ 2
- Mixed phenotype or undifferentiated leukemia in any CR
- Secondary to therapy-associated leukemia in any CR
- NK cell lineage leukemia in any CR
- Myelodysplastic syndrome (MDS)
- Juvenile myelomonocytic leukemia (JMML)
- May have undergone a prior hematopoietic stem cell transplant provided one of the criteria in Inclusion Criterion #1 are met AND the patient does not have active GVHD (has been off immunosuppression for at least 3 months).
- Available familial haploidentical donor.
- Donor and recipient must be identical at a minimum of one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA-DRB1, and HLA-DQB1. A minimum of 5/10 match is required and will be considered sufficient evidence that the donor and recipient share one HLA haplotype.
- No more than 30 years of age
- Lansky or Karnofksy performance status > 50%
Adequate organ function as defined below:
- Cardiac: LVEF ≥ 40% at rest or SF ≥ 26%
Hepatic:
- Total bilirubin < 3 x IULN for age
- AST(SGOT)/ALT(SGPT) < 5 x IULN
- Renal: GFR ≥ 60 mL/min/1.73m2 as estimated by updated Schwartz formula for ages 1-17 years (see Appendix B), 24 hour creatinine clearance, or renal scintigraphy. If GFR is abnormal for age based on updated Schwartz formula, accurate measurement should be obtained by either 24 hour creatinine clearance or renal scintigraphy. Renal function may also be estimated by serum creatinine based on age/gender. A minimum serum creatinine of 2x upper limit of normal is required for inclusion on this protocol.
Pulmonary:
- O2 saturation ≥ 92% on room air without positive pressure support
- FEV1, FVC, and DLCO ≥ 50% of predicted (for children unable to perform a pulmonary function test, a high-resolution CT chest may be obtained)
- The effects of these treatments on the developing human fetus are unknown. For this reason, patients of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for 24 months following transplant. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Recipient Exclusion Criteria:
- Available matched related donor. A patient with a matched unrelated donor is eligible if urgent transplantation is required. A prior unrelated donor search is not required for enrollment.
- Active non-hematologic malignancy. History of other malignancy is acceptable as long as therapy has been complete and there is no evidence of disease.
- Currently receiving any other investigational agents.
- Active CNS or extramedullary disease. History of CNS or extramedullary disease now in remission is acceptable.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to conditioning agents used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (bacterial, viral with clinical instability, or fungal), symptomatic congestive heart failure, or unstable cardiac arrhythmia.
- Presence of significant anti-donor HLA antibodies per institutional standards. Anti-donor HLA Antibody Testing is defined as a positive crossmatch test of any titer (by complement dependent cytotoxicity or flow cytometric testing) or the mean fluorescence intensity (MFI) of any anti-donor HLA antibody by solid phase immunoassay.
- Presence of a second major disorder deemed a contraindication for HSCT.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of the start of conditioning.
Donor Eligibility Criteria:
- At least 6 months of age
- Meets the selection criteria as defined by the Foundation for the Accreditation of Hematopoietic Cell Therapy (FACT).
The following criteria, in order of importance, should be considered for donor selection:
- Medically and psychologically fit and willing to donate
- ABO compatibility (in order of priority)
CMV status
**For a CMV seronegative recipient, use a CMV seronegative donor.
- Younger adults and non-obese donors should be preferred.
- If all else is equal, male donors may be preferred over nulliparous female donors who may be preferred over multiparous female donors
- Agree to donate PBSC.
- Able to understand and willing to sign an IRB-approved written informed consent document (or that of legally authorized representative, if applicable).
Sites / Locations
- Washington University School of MedicineRecruiting
Arms of the Study
Arm 1
Experimental
ex vivo αβ-TCR/CD19 depleted haplo-hematopoietic stem cell infusion (HSCT)
Patients will undergo standard of care conditioning regiment prior to HSCT On Day 0, patients will undergo infusion of the ex vivo αβ-TCR/CD19 depleted haplo-HSCT from a stimulated peripheral stem cell source per institutional standard of care. Patients whose graft has a residual CD20+ count > 1.0 x 10^5 may receive a single infusion of rituximab on Day +1 at a dose of 375 mg/m^2 at provider's discretion.