Trial Outcomes & Findings for NK Cell Based Non-Myeloablative Transplantation in Acute Myeloid Diseases (NCT NCT01370213)
NCT ID: NCT01370213
Last Updated: 2020-05-13
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
Day 28
Results posted on
2020-05-13
Participant Flow
Participant milestones
| Measure |
CD34+ Selection Schema : 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 filgrastim mobilized CD34+ selected peripheral blood stem cell graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5 (3 mg/kg/day) pre-tx.
|
TCR α/β Depletion Schema : 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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5(3 mg/kg/day) pre-tx.
|
TCR α/β Depletion and ATG at Different Time Schema
PPatients 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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered (3 mg/kg/day) pre-tx on different days per institutional guidelines
|
|---|---|---|---|
|
Overall Study
STARTED
|
7
|
17
|
1
|
|
Overall Study
COMPLETED
|
6
|
15
|
1
|
|
Overall Study
NOT COMPLETED
|
1
|
2
|
0
|
Reasons for withdrawal
| Measure |
CD34+ Selection Schema : 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 filgrastim mobilized CD34+ selected peripheral blood stem cell graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5 (3 mg/kg/day) pre-tx.
|
TCR α/β Depletion Schema : 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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5(3 mg/kg/day) pre-tx.
|
TCR α/β Depletion and ATG at Different Time Schema
PPatients 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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered (3 mg/kg/day) pre-tx on different days per institutional guidelines
|
|---|---|---|---|
|
Overall Study
Early Death
|
1
|
0
|
0
|
|
Overall Study
Not evaluable
|
0
|
2
|
0
|
Baseline Characteristics
NK Cell Based Non-Myeloablative Transplantation in Acute Myeloid Diseases
Baseline characteristics by cohort
| Measure |
CD34+ Selection Schema : High-Risk Acute Myeloid Disease
n=7 Participants
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 filgrastim mobilized CD34+ selected peripheral blood stem cell graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5(3 mg/kg/day) pre-tx.
|
TCR α/β Depletion Schema : High-Risk Acute Myeloid Disease
n=17 Participants
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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5(3 mg/kg/day) pre-tx.
|
TCR α/β Depletion and ATG at Different Time Schema
n=1 Participants
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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered (3 mg/kg/day) pre-tx on different days per institutional guidelines
|
Total
n=25 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Day 28Population: CD34 Schema - out of 7 patients, 2 patients were NA due to leukemia, 1 died, and 1 was not evaluable so 3 were analyzed (4 were not). TCRα/β Schema - out of 17 patients, 6 patients were NA due to leukemia, 2 were not evaluable. TCRα/β Schema + ATG - 1 patient was given ATG at a different time so their results were reported separately
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.
Outcome measures
| Measure |
CD34+ Selection Schema : High-Risk Acute Myeloid Disease
n=3 Participants
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 filgrastim mobilized CD34+ selected peripheral blood stem cell graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5(3 mg/kg/day) pre-tx.
|
TCR α/β Depletion Schema : High-Risk Acute Myeloid Disease
n=9 Participants
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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5(3 mg/kg/day) pre-tx.
|
TCR α/β Depletion and ATG at Different Time Schema
n=1 Participants
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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on different days per institutional guidelines
|
|---|---|---|---|
|
Number of Participants With Donor Neutrophil Engraftment
|
3 Participants
|
7 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: At 6 MonthsPopulation: CD34 Schema - of 7, 1 patient was not evaluable. TCRα/β Schema - of 17, 15 patients evaluable for DFS , 2 patients were not evaluable. TCRα/β Schema + ATG at different time - 1 patient given ATG at different time so results reported separately
Outcome measures
| Measure |
CD34+ Selection Schema : High-Risk Acute Myeloid Disease
n=6 Participants
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 filgrastim mobilized CD34+ selected peripheral blood stem cell graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5(3 mg/kg/day) pre-tx.
|
TCR α/β Depletion Schema : High-Risk Acute Myeloid Disease
n=15 Participants
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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5(3 mg/kg/day) pre-tx.
|
TCR α/β Depletion and ATG at Different Time Schema
n=1 Participants
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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on different days per institutional guidelines
|
|---|---|---|---|
|
Number of Participants With Disease Free Survival
|
1 Participants
|
6 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: At 6 MonthsPopulation: CD34 Schema - of 7 patients, 1 was not evaluable. TCRα/β Schema - of 17 patients, 8 died of disease, 2 did not have TRM at 6 months, 2 were not evaluable. TCRα/β Schema + ATG at different time - 1 patient given ATG at different time, results reported separately.
Cumulative incidence will be used to estimate TRM.
Outcome measures
| Measure |
CD34+ Selection Schema : High-Risk Acute Myeloid Disease
n=6 Participants
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 filgrastim mobilized CD34+ selected peripheral blood stem cell graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5(3 mg/kg/day) pre-tx.
|
TCR α/β Depletion Schema : High-Risk Acute Myeloid Disease
n=15 Participants
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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5(3 mg/kg/day) pre-tx.
|
TCR α/β Depletion and ATG at Different Time Schema
n=1 Participants
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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on different days per institutional guidelines
|
|---|---|---|---|
|
Number of Participants With Treatment Related Mortality (TRM)
|
2 Participants
|
5 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 2 YearsPopulation: CD34 Graft - of 7, 1 patient not evaluable, 2 patients did not clear disease, 2 died before 2 years. TCRα/β Schema - of 17, 7 didn't achieve remission, 2 died before 2 years, 2 were not evaluable. TCRα/β Schema + ATG at different time - 1 patient received ATG at different time, results reported separately.
Cumulative incidence will be used to estimate relapse.
Outcome measures
| Measure |
CD34+ Selection Schema : High-Risk Acute Myeloid Disease
n=2 Participants
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 filgrastim mobilized CD34+ selected peripheral blood stem cell graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5(3 mg/kg/day) pre-tx.
|
TCR α/β Depletion Schema : High-Risk Acute Myeloid Disease
n=6 Participants
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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5(3 mg/kg/day) pre-tx.
|
TCR α/β Depletion and ATG at Different Time Schema
n=1 Participants
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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on different days per institutional guidelines
|
|---|---|---|---|
|
Number of Participants Who Relapse
|
2 Participants
|
6 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Day 12Population: CD34 Graft - of 7, 1 NA due to missing data/tests not performed, 1 not evaluable. TCRα/β Schema - of 17 patients, 15 were evaluable for outcome measure criteria, 2 were not evaluable. TCRα/β Schema + ATG at different time - 1 given ATG at different time, results reported separately.
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.
Outcome measures
| Measure |
CD34+ Selection Schema : High-Risk Acute Myeloid Disease
n=5 Participants
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 filgrastim mobilized CD34+ selected peripheral blood stem cell graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5(3 mg/kg/day) pre-tx.
|
TCR α/β Depletion Schema : High-Risk Acute Myeloid Disease
n=15 Participants
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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on day -6 (0.5 mg/kg) and day -5(3 mg/kg/day) pre-tx.
|
TCR α/β Depletion and ATG at Different Time Schema
n=1 Participants
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 TCR α/β-depleted haploidentical graft from the same donor.
Preparative Regimen:
1\) fludarabine 40 mg/m\^2 x 4 doses on Days -22 through -19 pretransplant (pre-tx), 2) cyclophosphamide 50 mg/kg x 2 doses on Days -20 and -19 pre-tx, 3) total body irradiation 200 cGy twice a day (BID) (at least 6 hours apart) on Day -18 pre-tx NK Cells: CD3\^- CD19\^- selected, interleukin-2 (IL-2) activated, haploidentical donor natural killer (NK) cells infused on Day -17 pre-tx Interleukin-2: Interleukin-2 6 million units (MU) subcutaneously (SQ) every other day for 6 doses beginning evening of NK cell infusion Anti-thymocyte globulin: rabbit anti-thymocyte globulin will be administered on different days per institutional guidelines
|
|---|---|---|---|
|
Number of Participants With Early In Vivo Expansion of Natural Killer (NK) Cells
|
1 Participants
|
6 Participants
|
1 Participants
|
Adverse Events
High-Risk Acute Myeloid Disease
Serious events: 19 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
High-Risk Acute Myeloid Disease
n=25 participants at risk
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.
Data is reported in a combined manner because the AE data was originally reported in the older database as a single arm. Data was separated out for the outcome measures because there was still access to this data externally. At this point, we are unable to separate the individual instance of adverse events by arm because we cannot access the source data.
|
|---|---|
|
Cardiac disorders
Acute Coronary Syndrome
|
4.0%
1/25
|
|
Renal and urinary disorders
Acute Kidney Injury
|
12.0%
3/25
|
|
Respiratory, thoracic and mediastinal disorders
Adult Respiratory Distress Syndrome
|
4.0%
1/25
|
|
Cardiac disorders
Atrial Fibrillation
|
4.0%
1/25
|
|
Infections and infestations
Cytomegalovirus
|
12.0%
3/25
|
|
Blood and lymphatic system disorders
Disseminated Intravascular Coagulation
|
4.0%
1/25
|
|
Nervous system disorders
Encephalopathy
|
4.0%
1/25
|
|
General disorders
Fever
|
4.0%
1/25
|
|
General disorders
Graft Failure
|
4.0%
1/25
|
|
Cardiac disorders
Heart Failure
|
4.0%
1/25
|
|
General disorders
Hypocellular Bone Marrow
|
8.0%
2/25
|
|
Vascular disorders
Hypotension
|
8.0%
2/25
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
4.0%
1/25
|
|
Skin and subcutaneous tissue disorders
Maculo-Papular Rash
|
4.0%
1/25
|
|
General disorders
Multi-Organ Failure
|
4.0%
1/25
|
|
Gastrointestinal disorders
Nausea
|
4.0%
1/25
|
|
Cardiac disorders
Pericardial Effusion
|
4.0%
1/25
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
8.0%
2/25
|
|
General disorders
Disease Relapse
|
4.0%
1/25
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
8.0%
2/25
|
|
Eye disorders
Retrobulbar Optic Neuritis
|
4.0%
1/25
|
|
Infections and infestations
Sepsis
|
8.0%
2/25
|
|
Respiratory, thoracic and mediastinal disorders
Upper Respiratory Infection
|
4.0%
1/25
|
Other adverse events
| Measure |
High-Risk Acute Myeloid Disease
n=25 participants at risk
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.
Data is reported in a combined manner because the AE data was originally reported in the older database as a single arm. Data was separated out for the outcome measures because there was still access to this data externally. At this point, we are unable to separate the individual instance of adverse events by arm because we cannot access the source data.
|
|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
8.0%
2/25
|
|
Cardiac disorders
Acute Coronary Syndrome
|
4.0%
1/25
|
|
Renal and urinary disorders
Acute Kidney Injury
|
8.0%
2/25
|
|
Cardiac disorders
Atrial Fibrillation
|
8.0%
2/25
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
12.0%
3/25
|
|
Investigations
Creatinine Increased
|
8.0%
2/25
|
|
Gastrointestinal disorders
Dyspepsia
|
4.0%
1/25
|
|
Eye disorders
Eye Irritation
|
4.0%
1/25
|
|
Blood and lymphatic system disorders
Febrile Neutropenia
|
72.0%
18/25
|
|
Gastrointestinal disorders
Epigastric Pain
|
8.0%
2/25
|
|
Nervous system disorders
Headache
|
12.0%
3/25
|
|
Renal and urinary disorders
Urinary Frequency
|
4.0%
1/25
|
|
General disorders
Lethargy
|
4.0%
1/25
|
|
Skin and subcutaneous tissue disorders
Maculo-Papular Rash
|
4.0%
1/25
|
|
Musculoskeletal and connective tissue disorders
Shoulder Pain
|
4.0%
1/25
|
|
Gastrointestinal disorders
Nausea
|
12.0%
3/25
|
|
Psychiatric disorders
Vivid Dreams
|
4.0%
1/25
|
|
Skin and subcutaneous tissue disorders
Pustular Folliculitis, Scalp
|
4.0%
1/25
|
|
Cardiac disorders
Sinus Tachycardia
|
4.0%
1/25
|
|
Skin and subcutaneous tissue disorders
Skin Nodules
|
4.0%
1/25
|
|
Gastrointestinal disorders
Vomiting - Intermittent
|
4.0%
1/25
|
|
Investigations
Weight Gain
|
12.0%
3/25
|
|
Musculoskeletal and connective tissue disorders
Ankle Sprain
|
4.0%
1/25
|
|
Gastrointestinal disorders
Anorexia
|
4.0%
1/25
|
|
Gastrointestinal disorders
Ascites
|
4.0%
1/25
|
|
General disorders
Chills
|
96.0%
24/25
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
56.0%
14/25
|
|
General disorders
Edema
|
60.0%
15/25
|
|
General disorders
Erythema at Central Venous Catheter Site
|
4.0%
1/25
|
|
Infections and infestations
Eye Infection
|
4.0%
1/25
|
|
Musculoskeletal and connective tissue disorders
Facial, Jaw, Parotid Pain
|
4.0%
1/25
|
|
General disorders
Fever
|
76.0%
19/25
|
|
Musculoskeletal and connective tissue disorders
Foot Pain
|
4.0%
1/25
|
|
Gastrointestinal disorders
Gastrointestinal Bleeding
|
4.0%
1/25
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
4.0%
1/25
|
|
Vascular disorders
Hypertension
|
92.0%
23/25
|
|
Vascular disorders
Hypotension
|
4.0%
1/25
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
56.0%
14/25
|
|
Infections and infestations
Infection, NOS
|
4.0%
1/25
|
|
General disorders
Infusion Related Reaction
|
64.0%
16/25
|
|
General disorders
Injection Site Reaction
|
52.0%
13/25
|
|
Musculoskeletal and connective tissue disorders
Leg Weakness
|
4.0%
1/25
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis/Pulmonary Infiltrates
|
20.0%
5/25
|
|
Skin and subcutaneous tissue disorders
Rash
|
56.0%
14/25
|
|
Eye disorders
Vision Changes, NOS
|
4.0%
1/25
|
Additional Information
Dr. Jeffrey Miller
Masonic Cancer Center, University of Minnesota
Phone: 612-626-4024
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place