Trial Outcomes & Findings for Donor Natural Killer Cells and Aldesleukin in Treating Patients w/High Risk AML Undergoing Donor Stem Cell Transplant (NCT NCT00303667)

NCT ID: NCT00303667

Last Updated: 2017-12-28

Results Overview

Number of patients alive without evidence of disease at 6 months after transplant

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

50 participants

Primary outcome timeframe

Month 6

Results posted on

2017-12-28

Participant Flow

50 patients were originally enrolled; only 47 patients were treated. 4 patients received a natural killer cell (NK) infusion but did not get a transplant because of an early death.

Participant milestones

Participant milestones
Measure	SCT w/Donor Natural Killer Cells - Short Schema Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.	SCT w/Donor Natural Killer Cells - Extended Schema Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
Overall Study STARTED	8	39
Overall Study COMPLETED	8	35
Overall Study NOT COMPLETED	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	SCT w/Donor Natural Killer Cells - Short Schema Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.	SCT w/Donor Natural Killer Cells - Extended Schema Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
Overall Study Death	0	4

Baseline Characteristics

Donor Natural Killer Cells and Aldesleukin in Treating Patients w/High Risk AML Undergoing Donor Stem Cell Transplant

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SCT w/Donor Natural Killer Cells - Short Schema n=8 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.	SCT w/Donor Natural Killer Cells - Extended Schema n=39 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.	Total n=47 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
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	36 Participants n=7 Participants	44 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	16 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	23 Participants n=7 Participants	27 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	39 participants n=7 Participants	47 participants n=5 Participants

PRIMARY outcome

Timeframe: Month 6

Number of patients alive without evidence of disease at 6 months after transplant

Outcome measures

Outcome measures
Measure	SCT w/Donor Natural Killer Cells - Short Schema n=8 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.	SCT w/Donor Natural Killer Cells - Extended Schema n=39 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
Disease-free Survival at 6 Months	0 participants	4 participants

PRIMARY outcome

Timeframe: 1 Year

Number of patients alive without evidence of disease at 1 year after transplant

Outcome measures

Outcome measures
Measure	SCT w/Donor Natural Killer Cells - Short Schema n=8 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.	SCT w/Donor Natural Killer Cells - Extended Schema n=39 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
Disease-free Survival at 1 Year	0 participants	3 participants

SECONDARY outcome

Timeframe: 12 - 14 days after NK cell infusion

Population: The protocol was amended to add this endpoint after the 8 subjects were enrolled on the short schema. Thus the relevant samples to determine NK expansion were not collected. On the extended schema, 3 of 39 patients died prior to the day on which in vivo donor NK cell expansion was assessed. Thus only 36 patients were evaluable for that endpoint.

Number of patients with in vivo expansion of donor NK cells. In vivo expansion of NK cell is defined as detection of \>100 donor-derived NK cells per microliter of blood.

Outcome measures

Outcome measures
Measure	SCT w/Donor Natural Killer Cells - Short Schema Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.	SCT w/Donor Natural Killer Cells - Extended Schema n=36 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
In Vivo Expansion of a Donor NK Cells NK Cell Product	—	19 participants

SECONDARY outcome

Timeframe: Day 28

Population: On the short schema, 1 of the 8 patients, and on the extended schema, 6 of the 39 patients, died prior to Day 28, the day on which engraftment was assessed. Thus, only 7 and 33 patients respectively were evaluable for that endpoint.

Number of patients with graft failure defined as \<500 donor neutrophils count by day 28 in the absence of residual or relapsed leukemia

Outcome measures

Outcome measures
Measure	SCT w/Donor Natural Killer Cells - Short Schema n=7 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.	SCT w/Donor Natural Killer Cells - Extended Schema n=33 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
Number of Patients With Graft Failure	1 participants	4 participants

SECONDARY outcome

Timeframe: Month 6

Grade III-IV acute graft versus host disease is a severe short term complication created by infusion of donor cells into a foreign host

Outcome measures

Outcome measures
Measure	SCT w/Donor Natural Killer Cells - Short Schema n=8 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.	SCT w/Donor Natural Killer Cells - Extended Schema n=39 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
Incidence of Grade III-IV Acute Graft Versus Host Disease	0 participants	0 participants

SECONDARY outcome

Timeframe: Day 100

Death within the first 100 days related to treatment in patients without relapse or persistent disease.

Outcome measures

Outcome measures
Measure	SCT w/Donor Natural Killer Cells - Short Schema n=8 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.	SCT w/Donor Natural Killer Cells - Extended Schema n=39 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
Number of Patients With Treatment-Related Mortality	1 participants	13 participants

SECONDARY outcome

Timeframe: 1 Year

Chronic graft versus host disease is a severe long term complication created by infusion of donor cells into a foreign host

Outcome measures

Outcome measures
Measure	SCT w/Donor Natural Killer Cells - Short Schema n=8 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.	SCT w/Donor Natural Killer Cells - Extended Schema n=39 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
Incidence of Chronic Graft Versus Host Disease	0 participants	0 participants

SECONDARY outcome

Timeframe: 1 Year

Population: On the extended schema, 16/39 patients either did not clear their leukemia or died before relapse would have been detected (day 28), and thus were not evaluable for relapse.

Disease relapse is the recurrence of leukemia in patients who had cleared their leukemia after treatment. Patients with persistent leukemia are not evaluable for relapse.

Outcome measures

Outcome measures
Measure	SCT w/Donor Natural Killer Cells - Short Schema n=8 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.	SCT w/Donor Natural Killer Cells - Extended Schema n=23 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
Number of Patients With Disease Relapse	5 participants	12 participants

SECONDARY outcome

Timeframe: 1 Year

Post-transplant lymphoproliferative disorder (PTLD) is a virally-driven cancer of the lymphoid cells caused by immunosuppressive drugs taken after allogeneic stem cell transplantation to prevent or control graft versus host disease.

Outcome measures

Outcome measures
Measure	SCT w/Donor Natural Killer Cells - Short Schema n=8 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.	SCT w/Donor Natural Killer Cells - Extended Schema n=39 Participants Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
Incidence of Post-transplant Lymphoproliferative Disorder (PTLD)	0 participants	3 participants

Adverse Events

SCT w/Donor Natural Killer Cells - Extended Schema

Serious events: 38 serious events

Other events: 39 other events

Deaths: 0 deaths

SCT w/Donor Natural Killer Cells - Short Schema

Serious events: 8 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Sarah Cooley, M.D.

Masonic Cancer Center

Phone: 612-626-4024

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	SCT w/Donor Natural Killer Cells - Extended Schema n=39 participants at risk Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 35mg/m\^2), cyclophosphamide (administered on Days -15 and -16), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.	SCT w/Donor Natural Killer Cells - Short Schema n=8 participants at risk Patients with high risk myeloid malignancies undergoing allogeneic hematopoietic stem cell transplantation, receiving fludarabine phosphate (daily dose of 40mg/m\^2), cyclophosphamide (administered on Day -15 only), cyclosporin A, total body irradiation, natural killer cells, aldesleukin, and thymoglobulin.
General disorders Chills	100.0% 39/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	75.0% 6/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
Respiratory, thoracic and mediastinal disorders Cough	17.9% 7/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	25.0% 2/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
Respiratory, thoracic and mediastinal disorders Dyspnea	46.2% 18/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	50.0% 4/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
General disorders Edema	59.0% 23/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	50.0% 4/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
General disorders Fatigue	92.3% 36/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	75.0% 6/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
General disorders Fever	94.9% 37/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	62.5% 5/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
Vascular disorders Hypertension	12.8% 5/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	0.00% 0/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
Vascular disorders Hypotension	17.9% 7/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	0.00% 0/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
Respiratory, thoracic and mediastinal disorders Hypoxia	23.1% 9/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	0.00% 0/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
General disorders Injection Site Reaction	53.8% 21/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	0.00% 0/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
Musculoskeletal and connective tissue disorders Myalgia/Arthralgia	25.6% 10/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	62.5% 5/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
Gastrointestinal disorders Nausea	30.8% 12/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	75.0% 6/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
Respiratory, thoracic and mediastinal disorders Pneumonitis/Pulmonary Infiltrates	41.0% 16/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	0.00% 0/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
Skin and subcutaneous tissue disorders Rash/Desquamation	46.2% 18/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	0.00% 0/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
General disorders Sweats	33.3% 13/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	62.5% 5/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.
Gastrointestinal disorders Vomiting	25.6% 10/39 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.	50.0% 4/8 • Up to 3 years post IL-2 infusion. Adverse event collection for the purposes of this study will focus on targeted adverse events and unexpected adverse events (serious) at specific time points in relation to the NK cell infusion and post NK cell infusion IL-2 injections.