Repeat Transplantation for Relapsed or Refractory Hematologic Malignancies Following Prior Transplantation

PRIMARY OBJECTIVE:

- To estimate engraftment by day +42 post-transplant in patients who receive
CD45RA-depleted haploidentical donor progenitor cell transplantation following reduced
intensity conditioning regimen that includes haploidentical natural killer (NK) cells.

SECONDARY OBJECTIVES:

- Estimate the incidence of malignant relapse, event-free survival, and overall survival
at one-year post-transplantation.

- Estimate incidence and severity of acute and chronic (GvHD).

- Estimate the rate of transplant related mortality (TRM) in the first 100 days after
transplantation.

Blood progenitor cells will be collected from adult donors to be used for transplantation.
Donor cells will be processed and filtered in a laboratory at St. Jude using a machine
called the CliniMACS™ device, and later infused (transplanted) into the participant through
his/her veins.

Participants undergo a conditioning regimen beginning Day 21 prior to progenitor cell
transplantation that includes chemotherapy medications and natural killer cells in
preparation for transplantation. They will then receive T-cell depleted HPC transplant
followed by CD45RA-depleted HPC transplant the following day.

Inclusion Criteria:

- Age less than or equal to 21 years.

- One of the following hematologic malignancies that has relapsed or remains refractory
after prior allogeneic hematopoietic cell transplant (HCT):

- ALL, AML, Myeloid Sarcoma, CML, Juvenile myelomonocytic leukemia (JMML),
myelodysplastic syndrome (MDS), non-Hodgkin lymphoma (NHL)

- Has a suitable single haplotype matched (≥ 3 of 6) family member donor.

- Does not have any other active malignancy other than the one for which this
transplant is indicated.

- If prior central nervous system (CNS) leukemia, it must be treated and in CNS
complete remission (CR)

- Does not have current uncontrolled bacterial, fungal, or viral infection.

- Patient must fulfill pre-transplant evaluation:

- Left ventricular ejection fraction > 40%, or shortening fraction ≥ 25%.

- Creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m2.

- Forced vital capacity (FVC) ≥ 40% of predicted value; or pulse oximetry ≥ 92% on room
air if patient is unable to perform pulmonary function testing.

- Karnofsky or Lansky (age-dependent) performance score ≥ 50 (See Appendix A).

- Bilirubin ≤ 3 times the upper limit of normal for age.

- Alanine aminotransferase (ALT) ≤ 5 times the upper limit of normal for age.

- Not pregnant. If female with child bearing potential, must be confirmed by negative
serum or urine pregnancy test within 14 days prior to enrollment.

- Not breast feeding

- DONOR: At least single haplotype matched (≥ 3 of 6) family member

- DONOR: At least 18 years of age.

- DONOR: HIV negative.

- DONOR: Not pregnant as confirmed by negative serum or urine pregnancy test within 14
days prior to enrollment (if female).

- DONOR: Not breast feeding.

- DONOR: Regarding donation eligibility, is identified as either:

- Completed the process of donor eligibility determination as outlined in 21 CFR
1271 and agency guidance; OR

- Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of
urgent medical need completed by the principal investigator or physician
sub-investigator per 21 CFR 1271.