This pilot clinical trial studies whether a donor natural killer cell infusion can be safely used after autologous cluster of differentiation (CD)133+ selected stem cell transplant in treating younger patients with solid tumors or lymphomas that are likely to come back or spread. Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. An autologous transplant means that stem cells are collected from the patient's blood and stored. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Stem cell selection is used to separate stem cells from other cells collected, which may include tumor cells. A natural killer cell is a type of white blood cell that has small particles with enzymes that can kill tumor cells. Adding a haploidentical donor (partially matched family member donor) natural killer cell infusion after an autologous stem cell transplant may help treat younger patients with high risk solid tumors or lymphomas.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02130869.
PRIMARY OBJECTIVES:
I. To evaluate day +35 absolute neutrophil count (ANC) engraftment in autologous stem cell transplantation for high risk pediatric malignancies after stem cell selection and immunotherapy.
SECONDARY OBJECTIVES:
I. To estimate incidence of relapse, disease-free survival and overall survival.
II. To characterize lymphocyte and hematopoietic reconstitution in these patients.
III. To describe the characteristics of the stem cell and natural killer cell grafts.
IV. To estimate the overall survival of patients treated without stem cell manipulation or natural killer (NK) cell infusion due to off therapy criteria.
EXPLORATORY OBJECTIVES:
I. To describe the functional and phenotypic characteristics of both autologous and donor lymphocyte subsets.
OUTLINE: Patients are assigned to 1 of 3 treatment groups according to diagnosis.
GROUP A (neuroblastoma): Patients receive busulfan intravenously (IV) every 6 hours on days -6 to -3 and melphalan IV once daily (QD) on days -2 and -1. Patients then undergo CD133+ selected autologous stem cell transplant on day 0. Patients receive anti-GD2 monoclonal antibody hu14.18K322A IV over 4 hours QD on days 2-5, donor NK cells IV on day 4, and aldesleukin subcutaneously (SC) on days 3, 5, 7, 9, 11, and 13.
GROUP B (lymphoma): Patients receive bendamustine hydrochloride IV QD on days -7 and -6, etoposide phosphate IV QD and cytarabine IV QD on days -5 to -2, and melphalan IV QD on day -1. Patients then undergo CD133+ selected autologous stem cell transplant on day 0 and receive donor NK cells and aldesleukin as in Group A.
GROUP C (other tumors): Patients receive melphalan IV QD on days -8 to -5, etoposide phosphate IV QD on day -4, and carboplatin IV QD on days -4 to -2. Patients then undergo CD133+ selected autologous stem cell transplant on day 0 and receive donor NK cells and aldesleukin as in Group A.
After completion of study treatment, patients are followed up for 1 year.
Lead OrganizationSaint Jude Children's Research Hospital
Principal InvestigatorBrandon Matthew Triplett
