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
Neuroblastoma - Lymphoma - High-risk Tumor
Conditions: official terms
Lymphoma - Neuroblastoma
Conditions: Keywords
Autologous stem cell transplantation, Natural killer cells
Study Type
Study Phase
Phase 1
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: CD133+ selected autologous stem cell infusion Type: Device
Name: IL-2 Type: Biological
Name: hu14.18K322A Type: Biological
Name: Busulfan Type: Drug
Name: Melphalan Type: Drug
Name: GM-CSF Type: Biological
Name: Bendamustine Type: Drug
Name: Etoposide Type: Drug
Name: Cytarabine Type: Drug
Name: Carboplatin Type: Drug
Name: Haploidentical natural killer cell infusion Type: Device
Name: G-CSF Type: Biological
Name: Etoposide phosphate Type: Drug
Overall Status
This is a pilot clinical trial investigating the addition of haploidentical natural killer cell infusion to autologous stem cell transplantation. This intervention will be evaluated in children with high-risk solid tumors for whom autologous transplantation is indicated. Natural killer cells from a haploidentical family member will be given after high dose chemotherapy and positively selected autologous stem cells. In patients with neuroblastoma, the anti-GD2 antibody hu14.18K322A will also be given. The effect on normal hematopoietic cell recovery will be evaluated and survival of children treated with this approach will be determined.

The investigators expect to enroll 36 participants. Haploidentical family members (donors) will also be recruited to provide natural killer cells.
Detailed Description
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
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 21 Years
Minimum Age: N/A
Gender: Both
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.
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Status: Recruiting
Contact: Christine Hartford, MD - 866-278-5833 - referralinfo@stjude.org
Start Date
September 2014
Completion Date
September 2020
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page