Trial Outcomes & Findings for T-Cell Depleted Double UCB for Refractory AML (NCT NCT01464359)
NCT ID: NCT01464359
Last Updated: 2017-12-28
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
3 participants
Primary outcome timeframe
At 3 months
Results posted on
2017-12-28
Participant Flow
Participant milestones
| Measure |
Patients With Acute Myelogenous Leukemia
Allopurinol: start on Day -8 per institutional guidelines Fludarabine: give on Days -7, -6 and -5, 25 mg/m\^2 intravenously (IV) Cyclophosphamide: give on Days -7 and -6, 60 mg/kg IV along with mesna per institutional guidelines Total body irradiation: give on Days -5, -4, -3, and -2, 165 cGy twice daily Double T-cell depleted umbilical cord blood transplantation with activation of one of the units in interleukin-2 (IL-2): give on Day 0 IL-2: start on Day +3 and Day +60, 9 MU subcutaneously three times weekly for 6 doses
Alternate preparative therapy for patients not able to receive additional radiation
Levetiracetam (Keppra): begin on Day -10 per institutional guidelines Busulfan: give Day -9 through Day -6, 0.8 mg/kg (1.1 mg/kg if \<12 kg) IV every 6 hours Cyclophosphamide: give Day -5 through Day -2, 50 mg/kg/day IV along with mesna per institutional guidelines
|
|---|---|
|
Overall Study
STARTED
|
3
|
|
Overall Study
COMPLETED
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
T-Cell Depleted Double UCB for Refractory AML
Baseline characteristics by cohort
| Measure |
Patients With Acute Myelogenous Leukemia
n=3 Participants
Allopurinol: start on Day -8 per institutional guidelines Fludarabine: give on Days -7, -6 and -5, 25 mg/m\^2 intravenously (IV) Cyclophosphamide: give on Days -7 and -6, 60 mg/kg IV along with mesna per institutional guidelines Total body irradiation: give on Days -5, -4, -3, and -2, 165 cGy twice daily Double T-cell depleted umbilical cord blood transplantation with activation of one of the units in interleukin-2 (IL-2): give on Day 0 IL-2: start on Day +3 and Day +60, 9 MU subcutaneously three times weekly for 6 doses
Alternate preparative therapy for patients not able to receive additional radiation
Levetiracetam (Keppra): begin on Day -10 per institutional guidelines Busulfan: give Day -9 through Day -6, 0.8 mg/kg (1.1 mg/kg if \<12 kg) IV every 6 hours Cyclophosphamide: give Day -5 through Day -2, 50 mg/kg/day IV along with mesna per institutional guidelines
|
|---|---|
|
Age, Categorical
<=18 years
|
2 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At 3 monthsThe 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.
Outcome measures
| Measure |
Patients With Acute Myelogenous Leukemia
n=3 Participants
Allopurinol: start on Day -8 per institutional guidelines Fludarabine: give on Days -7, -6 and -5, 25 mg/m\^2 intravenously (IV) Cyclophosphamide: give on Days -7 and -6, 60 mg/kg IV along with mesna per institutional guidelines Total body irradiation: give on Days -5, -4, -3, and -2, 165 cGy twice daily Double T-cell depleted umbilical cord blood transplantation with activation of one of the units in interleukin-2 (IL-2): give on Day 0 IL-2: start on Day +3 and Day +60, 9 MU subcutaneously three times weekly for 6 doses
Alternate preparative therapy for patients not able to receive additional radiation
Levetiracetam (Keppra): begin on Day -10 per institutional guidelines Busulfan: give Day -9 through Day -6, 0.8 mg/kg (1.1 mg/kg if \<12 kg) IV every 6 hours Cyclophosphamide: give Day -5 through Day -2, 50 mg/kg/day IV along with mesna per institutional guidelines
|
|---|---|
|
Disease Free Survival
|
1 participants
|
SECONDARY outcome
Timeframe: Day 42Incidence 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)
Outcome measures
| Measure |
Patients With Acute Myelogenous Leukemia
n=3 Participants
Allopurinol: start on Day -8 per institutional guidelines Fludarabine: give on Days -7, -6 and -5, 25 mg/m\^2 intravenously (IV) Cyclophosphamide: give on Days -7 and -6, 60 mg/kg IV along with mesna per institutional guidelines Total body irradiation: give on Days -5, -4, -3, and -2, 165 cGy twice daily Double T-cell depleted umbilical cord blood transplantation with activation of one of the units in interleukin-2 (IL-2): give on Day 0 IL-2: start on Day +3 and Day +60, 9 MU subcutaneously three times weekly for 6 doses
Alternate preparative therapy for patients not able to receive additional radiation
Levetiracetam (Keppra): begin on Day -10 per institutional guidelines Busulfan: give Day -9 through Day -6, 0.8 mg/kg (1.1 mg/kg if \<12 kg) IV every 6 hours Cyclophosphamide: give Day -5 through Day -2, 50 mg/kg/day IV along with mesna per institutional guidelines
|
|---|---|
|
Incidence of Graft Failure
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 60Outcome measures
| Measure |
Patients With Acute Myelogenous Leukemia
n=3 Participants
Allopurinol: start on Day -8 per institutional guidelines Fludarabine: give on Days -7, -6 and -5, 25 mg/m\^2 intravenously (IV) Cyclophosphamide: give on Days -7 and -6, 60 mg/kg IV along with mesna per institutional guidelines Total body irradiation: give on Days -5, -4, -3, and -2, 165 cGy twice daily Double T-cell depleted umbilical cord blood transplantation with activation of one of the units in interleukin-2 (IL-2): give on Day 0 IL-2: start on Day +3 and Day +60, 9 MU subcutaneously three times weekly for 6 doses
Alternate preparative therapy for patients not able to receive additional radiation
Levetiracetam (Keppra): begin on Day -10 per institutional guidelines Busulfan: give Day -9 through Day -6, 0.8 mg/kg (1.1 mg/kg if \<12 kg) IV every 6 hours Cyclophosphamide: give Day -5 through Day -2, 50 mg/kg/day IV along with mesna per institutional guidelines
|
|---|---|
|
Incidence of Acute Graft-Versus-Host Disease
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 180 after TransplantationOutcome measures
| Measure |
Patients With Acute Myelogenous Leukemia
n=3 Participants
Allopurinol: start on Day -8 per institutional guidelines Fludarabine: give on Days -7, -6 and -5, 25 mg/m\^2 intravenously (IV) Cyclophosphamide: give on Days -7 and -6, 60 mg/kg IV along with mesna per institutional guidelines Total body irradiation: give on Days -5, -4, -3, and -2, 165 cGy twice daily Double T-cell depleted umbilical cord blood transplantation with activation of one of the units in interleukin-2 (IL-2): give on Day 0 IL-2: start on Day +3 and Day +60, 9 MU subcutaneously three times weekly for 6 doses
Alternate preparative therapy for patients not able to receive additional radiation
Levetiracetam (Keppra): begin on Day -10 per institutional guidelines Busulfan: give Day -9 through Day -6, 0.8 mg/kg (1.1 mg/kg if \<12 kg) IV every 6 hours Cyclophosphamide: give Day -5 through Day -2, 50 mg/kg/day IV along with mesna per institutional guidelines
|
|---|---|
|
Transplant-Related Mortality
|
0 Participants
|
SECONDARY outcome
Timeframe: 1 Year from TransplantationDefined 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.
Outcome measures
| Measure |
Patients With Acute Myelogenous Leukemia
n=3 Participants
Allopurinol: start on Day -8 per institutional guidelines Fludarabine: give on Days -7, -6 and -5, 25 mg/m\^2 intravenously (IV) Cyclophosphamide: give on Days -7 and -6, 60 mg/kg IV along with mesna per institutional guidelines Total body irradiation: give on Days -5, -4, -3, and -2, 165 cGy twice daily Double T-cell depleted umbilical cord blood transplantation with activation of one of the units in interleukin-2 (IL-2): give on Day 0 IL-2: start on Day +3 and Day +60, 9 MU subcutaneously three times weekly for 6 doses
Alternate preparative therapy for patients not able to receive additional radiation
Levetiracetam (Keppra): begin on Day -10 per institutional guidelines Busulfan: give Day -9 through Day -6, 0.8 mg/kg (1.1 mg/kg if \<12 kg) IV every 6 hours Cyclophosphamide: give Day -5 through Day -2, 50 mg/kg/day IV along with mesna per institutional guidelines
|
|---|---|
|
Clinical Disease Response
|
2 Participants
|
SECONDARY outcome
Timeframe: 6 months after Transplantation.Outcome measures
| Measure |
Patients With Acute Myelogenous Leukemia
n=3 Participants
Allopurinol: start on Day -8 per institutional guidelines Fludarabine: give on Days -7, -6 and -5, 25 mg/m\^2 intravenously (IV) Cyclophosphamide: give on Days -7 and -6, 60 mg/kg IV along with mesna per institutional guidelines Total body irradiation: give on Days -5, -4, -3, and -2, 165 cGy twice daily Double T-cell depleted umbilical cord blood transplantation with activation of one of the units in interleukin-2 (IL-2): give on Day 0 IL-2: start on Day +3 and Day +60, 9 MU subcutaneously three times weekly for 6 doses
Alternate preparative therapy for patients not able to receive additional radiation
Levetiracetam (Keppra): begin on Day -10 per institutional guidelines Busulfan: give Day -9 through Day -6, 0.8 mg/kg (1.1 mg/kg if \<12 kg) IV every 6 hours Cyclophosphamide: give Day -5 through Day -2, 50 mg/kg/day IV along with mesna per institutional guidelines
|
|---|---|
|
Duration of Survival
|
1 Participants
|
SECONDARY outcome
Timeframe: 1 year after Transplantation.Outcome measures
| Measure |
Patients With Acute Myelogenous Leukemia
n=3 Participants
Allopurinol: start on Day -8 per institutional guidelines Fludarabine: give on Days -7, -6 and -5, 25 mg/m\^2 intravenously (IV) Cyclophosphamide: give on Days -7 and -6, 60 mg/kg IV along with mesna per institutional guidelines Total body irradiation: give on Days -5, -4, -3, and -2, 165 cGy twice daily Double T-cell depleted umbilical cord blood transplantation with activation of one of the units in interleukin-2 (IL-2): give on Day 0 IL-2: start on Day +3 and Day +60, 9 MU subcutaneously three times weekly for 6 doses
Alternate preparative therapy for patients not able to receive additional radiation
Levetiracetam (Keppra): begin on Day -10 per institutional guidelines Busulfan: give Day -9 through Day -6, 0.8 mg/kg (1.1 mg/kg if \<12 kg) IV every 6 hours Cyclophosphamide: give Day -5 through Day -2, 50 mg/kg/day IV along with mesna per institutional guidelines
|
|---|---|
|
Duration of Survival
|
0 Participants
|
SECONDARY outcome
Timeframe: 2 years after Transplantation.Outcome measures
| Measure |
Patients With Acute Myelogenous Leukemia
n=3 Participants
Allopurinol: start on Day -8 per institutional guidelines Fludarabine: give on Days -7, -6 and -5, 25 mg/m\^2 intravenously (IV) Cyclophosphamide: give on Days -7 and -6, 60 mg/kg IV along with mesna per institutional guidelines Total body irradiation: give on Days -5, -4, -3, and -2, 165 cGy twice daily Double T-cell depleted umbilical cord blood transplantation with activation of one of the units in interleukin-2 (IL-2): give on Day 0 IL-2: start on Day +3 and Day +60, 9 MU subcutaneously three times weekly for 6 doses
Alternate preparative therapy for patients not able to receive additional radiation
Levetiracetam (Keppra): begin on Day -10 per institutional guidelines Busulfan: give Day -9 through Day -6, 0.8 mg/kg (1.1 mg/kg if \<12 kg) IV every 6 hours Cyclophosphamide: give Day -5 through Day -2, 50 mg/kg/day IV along with mesna per institutional guidelines
|
|---|---|
|
Duration of Survival
|
0 Participants
|
SECONDARY outcome
Timeframe: 2 Years from TransplantationDefined 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.
Outcome measures
| Measure |
Patients With Acute Myelogenous Leukemia
n=3 Participants
Allopurinol: start on Day -8 per institutional guidelines Fludarabine: give on Days -7, -6 and -5, 25 mg/m\^2 intravenously (IV) Cyclophosphamide: give on Days -7 and -6, 60 mg/kg IV along with mesna per institutional guidelines Total body irradiation: give on Days -5, -4, -3, and -2, 165 cGy twice daily Double T-cell depleted umbilical cord blood transplantation with activation of one of the units in interleukin-2 (IL-2): give on Day 0 IL-2: start on Day +3 and Day +60, 9 MU subcutaneously three times weekly for 6 doses
Alternate preparative therapy for patients not able to receive additional radiation
Levetiracetam (Keppra): begin on Day -10 per institutional guidelines Busulfan: give Day -9 through Day -6, 0.8 mg/kg (1.1 mg/kg if \<12 kg) IV every 6 hours Cyclophosphamide: give Day -5 through Day -2, 50 mg/kg/day IV along with mesna per institutional guidelines
|
|---|---|
|
Clinical Disease Response
|
2 Participants
|
Adverse Events
Patients With Acute Myelogenous Leukemia
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Patients With Acute Myelogenous Leukemia
n=3 participants at risk
Allopurinol: start on Day -8 per institutional guidelines Fludarabine: give on Days -7, -6 and -5, 25 mg/m\^2 intravenously (IV) Cyclophosphamide: give on Days -7 and -6, 60 mg/kg IV along with mesna per institutional guidelines Total body irradiation: give on Days -5, -4, -3, and -2, 165 cGy twice daily Double T-cell depleted umbilical cord blood transplantation with activation of one of the units in interleukin-2 (IL-2): give on Day 0 IL-2: start on Day +3 and Day +60, 9 MU subcutaneously three times weekly for 6 doses
Alternate preparative therapy for patients not able to receive additional radiation
Levetiracetam (Keppra): begin on Day -10 per institutional guidelines Busulfan: give Day -9 through Day -6, 0.8 mg/kg (1.1 mg/kg if \<12 kg) IV every 6 hours Cyclophosphamide: give Day -5 through Day -2, 50 mg/kg/day IV along with mesna per institutional guidelines
|
|---|---|
|
Infections and infestations
Infections and infestations - Other, blood culture w/gram positive cocci and CMV
|
33.3%
1/3
|
|
General disorders
fever
|
33.3%
1/3
|
|
Hepatobiliary disorders
hepatobilliary disorders - Other, veno occlusive disease
|
33.3%
1/3
|
Other adverse events
| Measure |
Patients With Acute Myelogenous Leukemia
n=3 participants at risk
Allopurinol: start on Day -8 per institutional guidelines Fludarabine: give on Days -7, -6 and -5, 25 mg/m\^2 intravenously (IV) Cyclophosphamide: give on Days -7 and -6, 60 mg/kg IV along with mesna per institutional guidelines Total body irradiation: give on Days -5, -4, -3, and -2, 165 cGy twice daily Double T-cell depleted umbilical cord blood transplantation with activation of one of the units in interleukin-2 (IL-2): give on Day 0 IL-2: start on Day +3 and Day +60, 9 MU subcutaneously three times weekly for 6 doses
Alternate preparative therapy for patients not able to receive additional radiation
Levetiracetam (Keppra): begin on Day -10 per institutional guidelines Busulfan: give Day -9 through Day -6, 0.8 mg/kg (1.1 mg/kg if \<12 kg) IV every 6 hours Cyclophosphamide: give Day -5 through Day -2, 50 mg/kg/day IV along with mesna per institutional guidelines
|
|---|---|
|
Blood and lymphatic system disorders
febrile neutropenia
|
100.0%
3/3
|
|
General disorders
chills
|
100.0%
3/3
|
|
General disorders
injection site reaction
|
66.7%
2/3
|
|
Hepatobiliary disorders
cholecystitis
|
33.3%
1/3
|
|
Injury, poisoning and procedural complications
bruising
|
33.3%
1/3
|
|
Nervous system disorders
Headache
|
66.7%
2/3
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
66.7%
2/3
|
|
Skin and subcutaneous tissue disorders
pain of skin
|
33.3%
1/3
|
|
Skin and subcutaneous tissue disorders
other, rash
|
66.7%
2/3
|
|
Vascular disorders
Hypertension
|
100.0%
3/3
|
|
Vascular disorders
Hypotension
|
33.3%
1/3
|
|
Vascular disorders
other, veno occlusive disease
|
33.3%
1/3
|
Additional Information
Michael R Verneris
University of Minnesota, Pediatrics Blood and Marrow Transplant
Phone: 612-626-2961
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place