Title (NCH 08-00234) A Multicenter Pilot Study of reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantation with In-Vivo T-Cell Depletion to Evaluate the Role of NK Cells and KIR Mis-Matches in Relapsed or Refractory High-Risk Neuroblastoma
Principal Investigator Barbara Bambach, MD
Study Number 174710
Summary This phase II pilot study is designed to confirm the feasibility of a RIC regimen for allogeneic HSCT for relapsed or refractory NBL patients. Toxicity, engraftment and incidence of severe GVHD will be monitored after HSCT. Class 1 mismatch donors will be selected for the HSCT and the KIR mis-matches in the donor-recepient pairs will be analyzed retrospectively, by utilizing the receptor-ligand model. The reconstituted donor NK cells repertoire will be followed by both the genotyping and phenotyping methods at multiple time-points post-transplant to better understand the NK cell reconstitution and alloreactivity against NBL. We will also study the cytotoxic effect of reconstituting NK cells on NBL cell lines to confirm the GVT effect. The major aim of this pilot study is to generate the preliminary clinical and laboratory data to confirm the feasibility of a RIC allogenetic HCST for heavily pre-treated NBL patients and elucidate the role of NK cells and KIR mis-matches in mediating the GVT effects against NBL.
- Age 1 to 18 years at the time of study enrollment.
- Female patients of childbearing potential must have a documented negative serum pregnancy test within 2 weeks prior to starting the preparative regimen.
- Performance status > 50 (Lansky/Karnofsky)
- Patients treated accordingly to COG A3973 or ANBL 0532 studies who after completion of induction have no response, mixed response, or progressive disease OR patietns who have relapsed following high-dose chemo-radiotherapy including autologous stem cell transplantion
- Disease status: Minimal residual disease status is preferred prior to study enrollment or status of the disease must be considered responsive to a salvage regimen or at least stable prior to enrollment. Patients with rapidly progressive disease are excluded. Patients should have achived CR, VGPR, or PR after_2 different salvage regimens. Patients receiving >2 different salvage regimens are not eligible for the study
- Patients that are in Complete Remission after salvage therapy are eligible for the study.
- Patients with the following prior therapies are eligible, with the following intervals from therapy to enrollment on this protocol: Prior autologous tranplant or myeloablative therapy > 2 months; Total Body Irradiation or whol abdominal radiation > months; local radiation to the sites of metastatic disease > 2weeks; patients must be > 3 weeks after and fully recovered from the toxic effects of any prior chemotherapy, immunotherapy (including anti-GD2 regimen), or biologic response modifiers, therapeutic 131I-MIBG> 2months.
- All organ function testing should be performed preferably within 2 weeks of study enrollment and must be within normal limits as specified in section 7.31 including adequate renal, liver, cardiac and pulmonary function.
- Exclusion Criteria:
- Patients with progressive disease or minimal response to salvage therapy regimens.
- Patients who ave received > 2 different salvage regimens
- Performance status < 50 (Karnofsky/Lansky scale).
- HIV Positive
- > 25% morphological replacement of BM by Neuroblastoma
- > 3 sites of MIBG positive skeletal disease
- Patients with proven or suspected sepsis, pneumonia or meningitis are not eligible for this protocol until appropriate therapeutic measures have been initiated to control the presumed or proven infection and systemic signs are no longer lifethreatening
- Patients who do not meet the organ function criteria defined in Section 7.31
- Patients with active or recent (within 30 days) fungal infections are excluded
- Patients receiving oxygen or ventilator support
- Previous Allogeneic HSCT