T-Cell Depleted Double UCB for Refractory AML
This trial is proposes to build on our experience and is designed to maximize early (day 3-14) and late (day 60-71) donor-derived natural killer (NK) cell expansion and function in vivo. The proposed platform will allow us the unique opportunity to compare in vivo function from a transplanted umbilical cord blood (UCB) source (presumed to contain NK progenitors requiring "education" in the recipient).
Acute Myelogenous Leukemia
Refractory Acute Myelogenous Leukemia
Radiation: Total body irradiation
Biological: Umbilical Cord Blood Transplantation
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: No ]
- Transplant-Related Mortality [ Time Frame: Day 180 after Transplantation ] [ Designated as safety issue: Yes ]
- Clinical Disease Response [ Time Frame: 1 Year from Transplantation ] [ Designated as safety issue: No ]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. ] [ Designated as safety issue: No ]
- Duration of Survival [ Time Frame: 1 year after Transplantation. ] [ Designated as safety issue: No ]
- Duration of Survival [ Time Frame: 2 years after Transplantation. ] [ Designated as safety issue: No ]
- Clinical Disease Response [ Time Frame: 2 Years from Transplantation ] [ Designated as safety issue: No ]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|
|Estimated Study Completion Date:||October 2016|
|Estimated Primary Completion Date:||October 2015 (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
This single center study will determine the feasibility and safety of using a myeloablative conditioning regimen followed (on day 0) by transplantation with double T-cell depleted (TCD) umbilical cord blood (UCB) units where the unit with fewer mononuclear cells (MNCs)/kg will be selected for overnight IL-2 activation prior to infusion. Beginning on day +3, post transplant IL-2 will be administered thrice weekly, not on consecutive days, for a total of 6 doses to expand UCB derived progenitor cells. Post transplant immune suppression prophylaxis will not be administered with the intent to lessen toxicity and allow allogeneic NK cells to function longer providing better anti-leukemic therapy. However if either UCB unit has more than 5% T-cells, the patient will not receive either course of IL-2. Beginning on day +60 after transplantation, a second course of IL-2 will be administered thrice weekly, not on consecutive days, for a total of 6 doses with the purpose of enhancing the in vivo expansion and education of NK cells derived from engrafting UCB cells.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01464359
|Contact: Timothy Krepski, RNemail@example.com|
|United States, Minnesota|
|Masonic Cancer Center, University of Minnesota||Recruiting|
|Minneapolis, Minnesota, United States, 55455|
|Contact: Timothy Krepski, RN 612-273-2800 firstname.lastname@example.org|
|Principal Investigator: Michael Verneris, M.D.|
|Principal Investigator:||Michael Verneris, M.D.||Masonic Cancer Center, University of Minnesota|