NK Cell Based Non-Myeloablative Transplantation in Acute Myeloid Diseases
This is a phase II multi-institutional therapeutic study of NK-cell based nonmyeloablative haploidentical transplantation for the treatment of high-risk acute myeloid diseases. Enrollment will use a two-stage design. Stage 1 will enroll 15 patients unless an early stopping rule is met. If 9 or more of these first 15 patients achieve leukemia free neutrophil engraftment at day +28 accrual will move to stage 2. In stage 2, an additional 28 patients will be enrolled for a total of 43 patients. Patients will be followed for disease response for 2 years.
Acute Myeloid Leukemia
Drug: Preparative Regimen
Biological: NK Cells
Biological: Anti-thymocyte globulin
Biological: Donor TCR α/β-depleted Cells
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Multi-Center Phase II Trial of NK Cell Based Non-Myeloablative Haploidentical Transplantation for Patients With High-Risk Acute Myeloid Diseases|
- Rate of Donor Neutrophil Engraftment [ Time Frame: Day 28 ] [ Designated as safety issue: No ]The rate of donor neutrophil engraftment in the absence of leukemia at day +28 will be determined. Successful neutrophil engraftment is defined as an absolute donor-derived neutrophil count of >500 cells/μl. Leukemia free is defined as <5% bone marrow blasts, absence of blasts with Auer rods; absence of extramedullary disease; but cytogenetic or molecular minimal residual disease is allowed.
- Disease Free Survival [ Time Frame: At 6 Months ] [ Designated as safety issue: No ]
- Treatment Related Mortality (TRM) [ Time Frame: At 6 Months ] [ Designated as safety issue: Yes ]Cumulative incidence will be used to estimate TRM.
- Incidence of Relapse [ Time Frame: 2 Years ] [ Designated as safety issue: No ]Cumulative incidence will be used to estimate relapse.
- Rate of Early In Vivo Expansion of Natural Killer (NK) Cells [ Time Frame: Day 0 ] [ Designated as safety issue: No ]Successful in vivo donor NK cell expansion will be defined by measuring an absolute circulating donor-derived NK cell count of >100 cells/μl in patient's peripheral blood 12 days after infusion.
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||September 2015|
|Estimated Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
Experimental: High-Risk Acute Myeloid Disease
Patients with high risk acute myeloid disease treated with preparative regimen including Fludara, Cytoxan and total body irradiation followed by haploidentical donor NK cells, Interleukin-2, rabbit anti-thymocyte globulin, and same donor TCR α/β-depleted cells infusion.
Drug: Preparative Regimen
1) fludarabine 40 mg/m^2 x 4 doses on Days -22 through -19 pretransplant, 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pretransplant, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pretransplant,
Other Names:Biological: NK Cells
CD3^- CD19^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pretransplant.
Other Name: Natural Killer cellsDrug: Interleukin-2
Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion
Other Name: IL-2Biological: Anti-thymocyte globulin
rabbit anti-thymocyte globulin will be administered on day -5 (0.5 mg/kg) and day -4 (2.5 mg/kg) pretransplant per institutional guidelines
Other Name: ATGBiological: Donor TCR α/β-depleted Cells
Single donor TCR α/β-depleted filgrastim-mobilized peripheral blood stem cells (PBSC) graft (minimum cell dose of 5 x 10^6/kg) on day 0
Other Name: stem cell graft
A reduced intensity conditioning using Fludara, Cytoxan, and irradiation will start on day -22, followed by infusion of donor NK (natural killer) cells on day-17, 6 doses of interleukin-2 (IL-2) to promote NK expansion (day -17 to day -7), 2 doses of ATG for additional immunosuppression to promote engraftment (day -5 to -4), and infusion of a TCR α/β-depleted same donor graft on day 0.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01370213
|Contact: Sarah Cooley, M.D.||email@example.com|
|United States, Georgia|
|Emory University||Not yet recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Edmund Waller, M.D.|
|Sub-Investigator: Edmund Waller, M.D.|
|United States, Minnesota|
|University of Minnesota, Masonic Cancer Center||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Timothy Krepski, RN 612-273-2800 firstname.lastname@example.org|
|Principal Investigator: Sarah Cooley, M.D.|
|United States, Missouri|
|Washington University||Not yet recruiting|
|St. Louis, Missouri, United States, 63110|
|Contact: John DiPersio, M.D.|
|Contact: Todd Fehninger|
|Principal Investigator: John DiPersio, M.D.|
|United States, Ohio|
|Ohio State University||Not yet recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Steven Devine, M.D.|
|Principal Investigator: Steven Devine, M.D.|
|Principal Investigator:||Sarah Cooley, M.D.||Masonic Cancer Center, University of Minnesota|