A Pilot Study of Immunotherapy Including Haploidentical NK Cell Infusion Following CD133+ Positively-Selected Autologous Hematopoietic Stem Cells in Children With High Risk Solid Tumors or Lymphomas

Primary Objective:

- To evaluate day +35 ANC engraftment in autologous stem cell transplantation for high
risk pediatric malignancies after stem cell selection and immunotherapy.

Secondary Objectives

- To estimate incidence of relapse, disease-free survival and overall survival.

- To characterize lymphocyte and hematopoietic reconstitution in these patients.

- To describe the characteristics of the stem cell and natural killer cell grafts.

- To estimate the overall survival of patients treated without stem cell manipulation or
NK cell infusion due to off therapy criteria

The transplant recipient will be evaluated for eligibility at two time points during study
participation. The first phase will be when the autologous stem cell product is collected.
The recipient will later need to meet specific eligibility criterion at the time of the
autologous stem cell infusion. The two phases and the respective criteria are described
below.

Inclusion criteria for autologous stem cell collection (Phase 1 - transplant recipient):

- Less than or equal to 21 years of age.

- Malignancy at high risk of treatment failure for which autologous hematopoietic stem
cell transplantation is considered within standard practice.

- Group A: High-risk neuroblastoma

- Group B: Recurrent or refractory Hodgkin lymphoma; recurrent or refractory
non-Hodgkin lymphoma

- Group C: High-risk, recurrent or metastatic sarcoma; recurrent or advanced stage
Wilms tumor; desmoplastic small round cell tumor; metastatic or recurrent
retinoblastoma, high-risk germ cell tumors, and high-risk brain tumors

- Sarcoma or Wilms tumor diagnosis (Group C) will require evaluation by physician in the
St. Jude Solid Tumor Division, other than the referring physician, attesting that
autologous SCT provides the prospect of direct benefit for the participant.

- Has a potentially suitable human leukocyte antigen (HLA) haploidentical donor
available.

- Research participant or legal guardian/representative must be willing to give written
informed consent

- Does not have any active or prior malignant or pre-malignant condition of the bone
marrow, excluding metastasis of the primary malignancy.

- Has no known allergy to murine products or positive human anti-mouse antibody (HAMA).

- (Female only) Negative serum or urine pregnancy test (to be conducted within 7 days
prior to enrollment).

- (Female only) Not breastfeeding.

Inclusion criteria to proceed with autologous stem cell transplantation (Phase 2 -
transplant recipient):

- Has a confirmed suitable HLA haploidentical donor available.

- Previously collected autologous stem cell product met the minimum collection target
and minimum infusion target as described in the protocol.

- At least two weeks since receipt of any biological therapy, chemotherapy, and/or
radiation therapy.

- Has recovered from all acute NCI Common Toxicity Criteria grade II-IV non-hematologic
toxicities from prior therapy per the judgment of the PI.

- Shortening fraction greater than or equal to 25%.

- Creatinine clearance or glomerular filtration rate greater than or equal to 50
mL/min/1.73 m^2.

- Pulse oximetry greater than or equal to 92% on room air.

- Alanine aminotransferase (ALT) and aspartate transaminase (AST) less than or equal to
3 times the upper limit of the institution-established normal range.

- Direct bilirubin less than or equal to 3.0 mg/dL.

- Karnofsky or Lansky performance score of greater than or equal to 50.

- Has not received a prior hematopoietic stem cell transplant within 3 months.

- Has no known allergy to murine products or positive human anti-mouse antibody (HAMA)

- (Female only) Is not pregnant (negative serum or urine pregnancy test to be conducted
within 7 days prior to admission for transplant).

- (Female only) Is not breastfeeding.

- Does not meet donation eligibility requirements as outlined by 21 CFR 1271 and agency
guidance.

Inclusion criteria for haploidentical NK cell donor:

- At least 18 years of age.

- Partially HLA matched family member.

- Human immunodeficiency virus (HIV) negative.

- (Female only) Is not pregnant (negative serum or urine pregnancy test to be conducted
within 7 days prior to enrollment).

- (Female only) Is not breastfeeding.