Trial Outcomes & Findings for Allogeneic Natural Killer Cells in Patients With Recurrent Ovarian Cancer, Fallopian Tube, and Primary Peritoneal Cancer (NCT NCT00652899)

NCT ID: NCT00652899

Last Updated: 2017-12-28

Results Overview

Detection of an absolute donor derived cell count of \> or = 100 cells/mL after NK cell infusion.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 14 participants
• Primary outcome timeframe: Day 12-14
• Results posted on: 2017-12-28

Participant Flow

Two patients did not receive all of study treatment per protocol.

Participant milestones

Measure	All Patients Enrolled This group includes all patients consented to participate in this study.
Overall Study STARTED	14
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	All Patients Enrolled This group includes all patients consented to participate in this study.
Overall Study Death	1
Overall Study Treating physician decision	1

Baseline Characteristics

Allogeneic Natural Killer Cells in Patients With Recurrent Ovarian Cancer, Fallopian Tube, and Primary Peritoneal Cancer

Baseline characteristics by cohort

Measure	All Patients Enrolled n=14 Participants This group includes all patients consented to participate in this study.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	55 years STANDARD_DEVIATION 5.19 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Region of Enrollment United States	14 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 12-14

Detection of an absolute donor derived cell count of > or = 100 cells/mL after NK cell infusion.

Outcome measures

Measure	Ovarian/Fallopian Tube/Peritoneal Cancer Patients n=12 Participants This group includes patients with recurrent ovarian, fallopian tube or primary peritoneal cancer who received at least one dose of chemotherapy (cyclophosphamide 60 mg/m\^2 and fludarabine 25 mg/m\^2 for 2 doses, and aldesleukin 10 million units for 6 doses), infusion of natural killer cells (1.5-8.0 \* 10\^7 kg) and/or total body irradiation per protocol (200 Gy on Day 1 preceding natural killer cell infusion).	Total Body Irradiation This group includes patients with recurrent ovarian, fallopian tube or primary peritoneal cancer who received at least one dose of chemotherapy (cyclophosphamide 60 mg/m\^2 and fludarabine 25 mg/m\^2 for 2 doses, and aldesleukin 10 million units for 6 doses), infusion of natural killer cells (1.5-8.0 \* 10\^7 kg) and total body irradiation (200 Gy on Day 1 preceding natural killer cell infusion).
Number of Patients With In Vivo Expansion of Infused Allogeneic Natural Killer (NK) Cell Product	0 Patients	—

SECONDARY outcome

Timeframe: 1 Month After Natural Killer Cell Infusion (Day 30)

Population: Includes 12 patients that completed treatment per protocol criteria.

Response Evaluation Criteria in Solid Tumors (RECIST) criteria: Complete Response (CR)-Disappearance of all target lesions (TL); Partial Response (PR)-< or = 30% decrease in the sum of the longest diameter (LD) of TL, reference baseline sum LD; Stable Disease (SD)-Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference the smallest sum LD since the treatment started; Progressive Disease (PD)- < or = 20% increase in the sum of the LD of TL, reference the smallest sum LD recorded since treatment started or appearance of < or = 1 new lesion.

Outcome measures

Measure	Ovarian/Fallopian Tube/Peritoneal Cancer Patients n=7 Participants This group includes patients with recurrent ovarian, fallopian tube or primary peritoneal cancer who received at least one dose of chemotherapy (cyclophosphamide 60 mg/m\^2 and fludarabine 25 mg/m\^2 for 2 doses, and aldesleukin 10 million units for 6 doses), infusion of natural killer cells (1.5-8.0 \* 10\^7 kg) and/or total body irradiation per protocol (200 Gy on Day 1 preceding natural killer cell infusion).	Total Body Irradiation n=5 Participants This group includes patients with recurrent ovarian, fallopian tube or primary peritoneal cancer who received at least one dose of chemotherapy (cyclophosphamide 60 mg/m\^2 and fludarabine 25 mg/m\^2 for 2 doses, and aldesleukin 10 million units for 6 doses), infusion of natural killer cells (1.5-8.0 \* 10\^7 kg) and total body irradiation (200 Gy on Day 1 preceding natural killer cell infusion).
Number of Patients Per Disease Response Complete Response	0 Patients	0 Patients
Number of Patients Per Disease Response Partial Response	2 Patients	1 Patients
Number of Patients Per Disease Response Stable Disease	4 Patients	4 Patients
Number of Patients Per Disease Response Progressive Disease	1 Patients	0 Patients

SECONDARY outcome

Timeframe: From date of first treatment to disease progression

Median number of days from first date of treatment to date of disease progression (appearance of new metastatic lesions or objective tumor progression). Defined by computated tomography (CT) imaging based on Response Evaluation Criteria In Solid Tumors (RECIST): Progressive Disease (PD) > or = 20% increase in sum of all target or any new lesions.

Outcome measures

Measure	Ovarian/Fallopian Tube/Peritoneal Cancer Patients n=7 Participants This group includes patients with recurrent ovarian, fallopian tube or primary peritoneal cancer who received at least one dose of chemotherapy (cyclophosphamide 60 mg/m\^2 and fludarabine 25 mg/m\^2 for 2 doses, and aldesleukin 10 million units for 6 doses), infusion of natural killer cells (1.5-8.0 \* 10\^7 kg) and/or total body irradiation per protocol (200 Gy on Day 1 preceding natural killer cell infusion).	Total Body Irradiation n=5 Participants This group includes patients with recurrent ovarian, fallopian tube or primary peritoneal cancer who received at least one dose of chemotherapy (cyclophosphamide 60 mg/m\^2 and fludarabine 25 mg/m\^2 for 2 doses, and aldesleukin 10 million units for 6 doses), infusion of natural killer cells (1.5-8.0 \* 10\^7 kg) and total body irradiation (200 Gy on Day 1 preceding natural killer cell infusion).
Median Number of Days to Progression	107 Days Interval 8.0 to 200.0	90 Days Interval 69.0 to 130.0

SECONDARY outcome

Timeframe: From first date on-study (treatment) to date of death

Median number of days patients alive from date of treatment to date of death or date of last follow-up if censored.

Outcome measures

Measure	Ovarian/Fallopian Tube/Peritoneal Cancer Patients n=5 Participants This group includes patients with recurrent ovarian, fallopian tube or primary peritoneal cancer who received at least one dose of chemotherapy (cyclophosphamide 60 mg/m\^2 and fludarabine 25 mg/m\^2 for 2 doses, and aldesleukin 10 million units for 6 doses), infusion of natural killer cells (1.5-8.0 \* 10\^7 kg) and/or total body irradiation per protocol (200 Gy on Day 1 preceding natural killer cell infusion).	Total Body Irradiation n=7 Participants This group includes patients with recurrent ovarian, fallopian tube or primary peritoneal cancer who received at least one dose of chemotherapy (cyclophosphamide 60 mg/m\^2 and fludarabine 25 mg/m\^2 for 2 doses, and aldesleukin 10 million units for 6 doses), infusion of natural killer cells (1.5-8.0 \* 10\^7 kg) and total body irradiation (200 Gy on Day 1 preceding natural killer cell infusion).
Median Overall Survival Number of Days Patients Alive After Treatment	171.5 Days Interval 144.0 to 199.0	291 Days Interval 8.0 to 301.0

Adverse Events

All Patients Enrolled

Serious events: 9 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Measure	All Patients Enrolled n=14 participants at risk This group includes all patients consented to participate in this study.
Respiratory, thoracic and mediastinal disorders Aspiration	7.1% 1/14 • Number of events 1 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
General disorders Constitutional symptoms	7.1% 1/14 • Number of events 2 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
General disorders Death - disease progression NOS	35.7% 5/14 • Number of events 5 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Blood and lymphatic system disorders Hemolysis	7.1% 1/14 • Number of events 1 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Respiratory, thoracic and mediastinal disorders Hypoxia	7.1% 1/14 • Number of events 1 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Infections and infestations Infection	7.1% 1/14 • Number of events 1 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Infections and infestations Infection - febrile neutropenia	7.1% 1/14 • Number of events 1 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Cardiac disorders Left ventricular systolic dysfunction	7.1% 1/14 • Number of events 1 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Gastrointestinal disorders Pain - abdomen NOS	7.1% 1/14 • Number of events 1 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
General disorders Tumor lysis syndrome	7.1% 1/14 • Number of events 1 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.

Other adverse events

Measure	All Patients Enrolled n=14 participants at risk This group includes all patients consented to participate in this study.
Respiratory, thoracic and mediastinal disorders Dyspnea	42.9% 6/14 • Number of events 23 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
General disorders Fever	85.7% 12/14 • Number of events 42 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
General disorders Chills	85.7% 12/14 • Number of events 44 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Cardiac disorders Hypertension	7.1% 1/14 • Number of events 8 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
General disorders Fatigue	92.9% 13/14 • Number of events 115 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Blood and lymphatic system disorders Edema	42.9% 6/14 • Number of events 29 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Respiratory, thoracic and mediastinal disorders Pneumonia	21.4% 3/14 • Number of events 17 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Skin and subcutaneous tissue disorders Injection Site Reaction	78.6% 11/14 • Number of events 58 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Skin and subcutaneous tissue disorders Rash	78.6% 11/14 • Number of events 45 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Respiratory, thoracic and mediastinal disorders Cough	35.7% 5/14 • Number of events 18 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Gastrointestinal disorders Vomiting	78.6% 11/14 • Number of events 30 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Gastrointestinal disorders Nausea	85.7% 12/14 • Number of events 80 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Musculoskeletal and connective tissue disorders Myalgia	64.3% 9/14 • Number of events 28 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Skin and subcutaneous tissue disorders Sweats	71.4% 10/14 • Number of events 27 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Blood and lymphatic system disorders Positive blood culture with fever	14.3% 2/14 • Number of events 5 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.
Blood and lymphatic system disorders Hemolysis	7.1% 1/14 • Number of events 1 • Serious adverse events were monitored through the follow-up period; death was followed for up to 2 years after Day 1 treatment. Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.

Additional Information

Melissa Geller, M.D.

University of Minnesota, Dept. Ob/Gyn

Phone: 612-626-3111

Email: gelle005@umn.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place