T-Cell Depleted Double UCB for Refractory AML
|Acute Myelogenous Leukemia Refractory Acute Myelogenous Leukemia||Drug: Allopurinol Drug: Fludarabine Radiation: Total body irradiation Drug: Cyclophosphamide Drug: Levetiracetam Drug: Busulfan Biological: Umbilical Cord Blood Transplantation Biological: Interleukin-2||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||T-Cell Depleted Double UCB With Post Transplant IL-2 for Refractory Myeloid Leukemia|
- Disease Free Survival [ Time Frame: At 3 months ]The primary endpoint is a disease free survival at 3 months in patients with chemotherapy refractory AML after a double T-cell depleted (TCD) umbilical cord blood (UCB) transplantation where one TCD unit is activated overnight in IL-2 followed by the administration of two courses of IL-2 three times a week for 6 doses beginning on day +3 and on day +60 to expand UCB-derived NK cells in vivo.
- Incidence of Graft Failure [ Time Frame: Day 42 ]Incidence of graft failure defined as an absolute neutrophil count of less than 500/uL and a bone marrow that is less than 5% cellular (marrow aplasia)
- Incidence of Acute Graft-Versus-Host Disease [ Time Frame: Day 60 ]
- Transplant-Related Mortality [ Time Frame: Day 180 after Transplantation ]
- Clinical Disease Response [ Time Frame: 1 Year from Transplantation ]Defined as leukemia clearance and complete remission. Patients will be followed for disease response for 1 year from transplantation unless: consent is withdrawal, patient is unevaluable - if a patient is not evaluable, follow only until the resolution or stabilization of treatment related toxicity, new anti-cancer treatment is started, patient is discharged to hospice (terminal) care.
- Duration of Survival [ Time Frame: 6 months after Transplantation. ]
- Duration of Survival [ Time Frame: 1 year after Transplantation. ]
- Duration of Survival [ Time Frame: 2 years after Transplantation. ]
- Clinical Disease Response [ Time Frame: 2 Years from Transplantation ]Defined as leukemia clearance and complete remission. Patients will be followed for disease response for 2 years from transplantation unless: consent is withdrawal, patient is unevaluable - if a patient is not evaluable, follow only untilthe resolution or stabilization of treatment related toxicity, new anti-cancer treatment is started, patient is discharged to hospice (terminal) care.
|Study Start Date:||October 2011|
|Study Completion Date:||October 2013|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Experimental: Patients with Acute Myelogenous Leukemia
Patients with chemotherapy refractory Acute Myelogenous Leukemia (AML) after a double T-cell depleted (TCD) umbilical cord blood (UCB) transplantation where the smaller unit is activated overnight in interleukin-2 (IL-2). IL-2 will be given three times weekly for 6 doses beginning on days+3 and days +60 to expand UCB-derived natural killer (NK) cells in vivo.
On Day 8 pre-transplant, start hydration with allopurinol per standard of care.
Other Name: ZyloprimDrug: Fludarabine
On Days 7, 6 and 5 pre-transplant, 25 mg/m^2 intravenously over 1 hour.
Other Name: FludaraRadiation: Total body irradiation
On Days 5, 4, 3, and 2 pre-transplant, 165 cGy times 2 (330 cGy daily, 1320 total dose) according to the University Of Minnesota Blood and Marrow Transplant Program total body irradiation (TBI) guidelines.
Other Name: RadiationDrug: Cyclophosphamide
On Days 7 and 6 pre-transplant, 60 mg/kg intravenously (IV) over 2 hours with a high volume fluid flush and mesna per institutional guidelines.
Alternate Preparative Therapy For Patients Not Able To Receive TBI: Days 5, 4, 3 and 2 pre-transplant; 50 mg/kg/day IV over 2 hours.
Other Name: CytoxanDrug: Levetiracetam
Alternate Preparative Therapy for Patients Not Able to Receive Total Body Irradiation (TBI): Hydration therapy on Day 10 pre-transplant.
Other Name: KeppraDrug: Busulfan
Alternate Preparative Therapy For Patients Not Able To Receive TBI: Days 9, 8, 7 and 6 pre-transplant; 0.8 mg/kg (1.1 mg/kg if <12 kg) intravenously every 6 hours
Other Name: MyleranBiological: Umbilical Cord Blood Transplantation
Day 0: Two UCB units will compose the graft. The infusion of the first UCB unit should begin within 15 minutes, and no later than 30 minutes after arrival on the Unit. The UCB unit without IL-2 activation will be infused first, followed by the IL-2 activated unit. Both cords will be infused within 30-60 minutes of each other as deemed clinically safe by the BMT attending.
Other Name: UCBTBiological: Interleukin-2
First Course of IL-2 (begin day +3) post-transplant: For patients ≥ 45 kg, IL-2 will be given at 9 million units every other day for a total of 6 doses subcutaneously. Patients weighing less than 45 kilograms, the IL-2 will be dosed at 5 million units/m^2 every other day for a total of 6 doses.
Second Course of IL-2 (day +60):
Patients will receive a second course of IL-2 beginning on Day +60 post transplant to expand and educate the NK cells derived from the UCB graft source.
Other Name: IL-2
Please refer to this study by its ClinicalTrials.gov identifier: NCT01464359
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Michael Verneris, M.D.||Masonic Cancer Center, University of Minnesota|