A Phase I Study of NK Cell Infusion Following Allogeneic Peripheral Blood Stem Cell Transplantation From Related or Matched Unrelated Donors in Pediatric Patients With Solid Tumors and Leukemias
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Kristin Baird, M.D.
1-877-624-4878 (Toll free)
- Despite progress in pediatric oncology, some patient subsets with hematologic malignancies and pediatric solid tumors continue to experience extremely poor overall survival; allogeneic hematopoietic stem cell transplant (HSCT) is effective in some high-risk hematologic malignancies, and studies of allogeneic HSCT conducted within the Pediatric Oncology Branch (POB) for ultra high-risk pediatric solid tumors have shown some promise
- Non-myeloablative allogeneic HSCT can be performed safely in these patient populations, but disease recurrence is common, and new approaches to enhance the antitumor effect of this therapy are needed; NK-mediated killing appears to confer improved outcomes after HSCT for patients with AML and ALL, and NK cell infusions have induced complete remissions in patients with AML
- Preclinical data demonstrates that activated NK cells readily kill pediatric solid tumors and leukemias; that large numbers of activated NK cells can be generated ex vivo using artificial APCs; and that the post-transplant period may be favorable for expansion and survival of adoptively transferred NK cells
- Primary objectives:
- Assess the feasibility and toxicity of infusing escalating doses of donor-derived activated NK cell donor lymphocyte infusions (NK-DLI) on Days 7 ± 3 days and 35 ± 7 days following HLA-matched T cell depleted (TCD) PBSCT in patients with metastatic or recurrent pediatric solid tumors and high-risk leukemias
- Determine if patients treated in this manner experience rapid, sustained donor engraftment and acceptable rates of aGVHD (< 25 percent incidence of Grade III or Grade IV)
- Secondary objectives:
- Assess DFS and OS of patients treated on this study; the incidence of cGVHD and viral infection; and evaluate biologic correlates of NK expansion and NK activity
Key Eligibility Criteria:
- Patients 4–35 years of age with pediatric solid tumors(ultra high risk; Ewing sarcoma family tumors (ESFT), rhabdomyosarcoma (RMS), desmoplastic small round cell tumor or neuroblastoma (NB)
- Patients 4–35 years of age with hematologic malignancies; acute lymphocytic (lymphoblastic) leukemia (ALL), acute myeloid leukemia (AML), Hodgkin disease (HD), non-Hodgkin lymphoma (NHL)
- 5/6 or 6/6 HLA-matched related or 10/10 HLA matched unrelated donor
- Patients with ALL and AML must be ineligible for a myeloablative HSCT
- Pre-transplant disease-specific immune depleting chemotherapy and the preparative regimen will be the same as that used previously on 02-C-0259 and 01-C-0125
- Donors will undergo a single apheresis for filgrastim mobilized PBSC; this product will be T cell and NK cell depleted prior to cryopreservation; NK cells selected from the product will be used for ex vivo activation and expansion using KT64.4-BBL artificial antigen presenting cells
- A Phase 1 cell dose escalation of donor derived NK-DLI will be performed using three dose levels (1 x 105, 1 x 106, and 1 x 107 NK cells/kg) infused on Days 7 ± 2 post-PBSCT and a second infusion 28 days ± 2 following the first
- Three patients will be enrolled at each dose level, with the cohort expanded to six if dose-limiting toxicity occurs; an expanded group of 12 patients will be treated at dose level 3
- This trial will be conducted at the NIH Clinical Center in Bethesda, MD. It is open to patients who meet the eligibility requirements, regardless of where they live in the United States.
- There is no charge for medical care received at NIH Clinical Center.
- PDQ (Physicians Data Query) - provides additional details about this study for health care providers.