Trial Outcomes & Findings for Donor Natural Killer Cell Infusion, Rituximab, Aldesleukin, and Chemotherapy in Treating Patients With Relapsed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia (NCT NCT00625729)

NCT ID: NCT00625729

Last Updated: 2017-12-28

Results Overview

Successful natural killer (NK) cell expansion will be defined as an absolute circulating donor-derived NK cell count of \>100 cells/μl 14 days after infusion with \<5% donor T and B cells in the mononuclear population.

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 6 participants
• Primary outcome timeframe: Day 14
• Results posted on: 2017-12-28

Participant Flow

Participant milestones

Measure	Patients Treated With Natural Killer Cells Patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with 1 dose donor natural killer cells infusion, 4 doses rituximab, 6 doses aldesleukin and 5 doses fludarabine and 1 dose cyclosphosphamide.
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Donor Natural Killer Cell Infusion, Rituximab, Aldesleukin, and Chemotherapy in Treating Patients With Relapsed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia

Baseline characteristics by cohort

Measure	Patients Treated With Natural Killer Cells n=6 Participants Patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with 1 dose donor natural killer cells infusion, 4 doses rituximab, 6 doses aldesleukin and 5 doses fludarabine and 1 dose cyclosphosphamide.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Age, Continuous	52.2 years STANDARD_DEVIATION 13.6 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 14

Successful natural killer (NK) cell expansion will be defined as an absolute circulating donor-derived NK cell count of >100 cells/μl 14 days after infusion with <5% donor T and B cells in the mononuclear population.

Outcome measures

Measure	Patients Treated With Natural Killer Cells n=6 Participants Patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with 1 dose donor natural killer cells infusion, 4 doses rituximab, 6 doses aldesleukin and 5 doses fludarabine and 1 dose cyclosphosphamide.
Number of Patients Exhibiting Natural Killer Cell Expansion	0 Participants

SECONDARY outcome

Timeframe: Day 0

Population: Correlation of interleukin-15 with Natural Killer Cell expansion cannot be calculated because there was no Natural Killer Cell expansion.

Correlation of interleukin-15 production at day 0 with natural killer (NK) cells expansion

Outcome measures

Measure	Patients Treated With Natural Killer Cells n=6 Participants Patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with 1 dose donor natural killer cells infusion, 4 doses rituximab, 6 doses aldesleukin and 5 doses fludarabine and 1 dose cyclosphosphamide.
Number of Patients With Interleukin-15 Production and NK Cell Expansion	0 Participants

SECONDARY outcome

Timeframe: 3 Months

Overall response (complete remission plus partial remission) rate at 3 months, as defined by International Working Group for non-Hodgkin lymphoma and NCI Working Group guidelines for chronic lymphocytic leukemia

Outcome measures

Measure	Patients Treated With Natural Killer Cells n=6 Participants Patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with 1 dose donor natural killer cells infusion, 4 doses rituximab, 6 doses aldesleukin and 5 doses fludarabine and 1 dose cyclosphosphamide.
Number of Patients With Overall Response	4 Participants

SECONDARY outcome

Timeframe: 6 Months

Population: Only patients who responded to treatment included in the analysis.

Includes patients (with non-Hodgkin leukemia or chronic lymphocytic leukemia) whose disease progressed after treatment.

Outcome measures

Measure	Patients Treated With Natural Killer Cells n=4 Participants Patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with 1 dose donor natural killer cells infusion, 4 doses rituximab, 6 doses aldesleukin and 5 doses fludarabine and 1 dose cyclosphosphamide.
Number of Patients Whose Disease Progressed After Treatment	2 Participants

SECONDARY outcome

Timeframe: Day 0

Incidence of donor products that met release criteria in accordance with FDA regulations (Lot Release Criteria for allogeneic, interleukin-2 (IL-2) activated natural killer (NK) cell products (BB-IND 8847) and the NK cell numbers infused (donor NK cell dose 1.5-8.0 x 10^7/kg).

Outcome measures

Measure	Patients Treated With Natural Killer Cells n=6 Participants Patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with 1 dose donor natural killer cells infusion, 4 doses rituximab, 6 doses aldesleukin and 5 doses fludarabine and 1 dose cyclosphosphamide.
Number of Patients With Adequate Natural Killer Cells Infused	6 Participants

SECONDARY outcome

Timeframe: 6 Months

Number of patients alive at 6 months after treatment.

Outcome measures

Measure	Patients Treated With Natural Killer Cells n=6 Participants Patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with 1 dose donor natural killer cells infusion, 4 doses rituximab, 6 doses aldesleukin and 5 doses fludarabine and 1 dose cyclosphosphamide.
Number of Patients With Overall Survival	3 Participants

Adverse Events

Patients Treated With Natural Killer Cells

Serious events: 5 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Patients Treated With Natural Killer Cells n=6 participants at risk Patients with relapsed non-Hodgkin lymphoma or chronic lymphocytic leukemia treated with 1 dose donor natural killer cells infusion, 4 doses rituximab, 6 doses aldesleukin and 5 doses fludarabine and 1 dose cyclosphosphamide.
Cardiac disorders Cardiac Arrhythmia	16.7% 1/6 • Number of events 1 • Serious adverse events were collected after start of chemotherapy treatment (Day -1) through date of death (all within 6 months). Stopping Rules for excess toxicity: * Any non-hematologic grade 4 toxicity except for fevers alone * Grade III/IV GvHD or GvHD requiring more than 7 days of therapy * Hematologic toxicity: prolonged neutropenia defined as an absolute neutrophil count of less than 500 on day +35. Prolonged anemia or thrombocytopenia will not constitute toxicity.
General disorders Death - Disease Progression NOS	50.0% 3/6 • Number of events 3 • Serious adverse events were collected after start of chemotherapy treatment (Day -1) through date of death (all within 6 months). Stopping Rules for excess toxicity: * Any non-hematologic grade 4 toxicity except for fevers alone * Grade III/IV GvHD or GvHD requiring more than 7 days of therapy * Hematologic toxicity: prolonged neutropenia defined as an absolute neutrophil count of less than 500 on day +35. Prolonged anemia or thrombocytopenia will not constitute toxicity.
Infections and infestations Infection	33.3% 2/6 • Number of events 2 • Serious adverse events were collected after start of chemotherapy treatment (Day -1) through date of death (all within 6 months). Stopping Rules for excess toxicity: * Any non-hematologic grade 4 toxicity except for fevers alone * Grade III/IV GvHD or GvHD requiring more than 7 days of therapy * Hematologic toxicity: prolonged neutropenia defined as an absolute neutrophil count of less than 500 on day +35. Prolonged anemia or thrombocytopenia will not constitute toxicity.
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	16.7% 1/6 • Number of events 1 • Serious adverse events were collected after start of chemotherapy treatment (Day -1) through date of death (all within 6 months). Stopping Rules for excess toxicity: * Any non-hematologic grade 4 toxicity except for fevers alone * Grade III/IV GvHD or GvHD requiring more than 7 days of therapy * Hematologic toxicity: prolonged neutropenia defined as an absolute neutrophil count of less than 500 on day +35. Prolonged anemia or thrombocytopenia will not constitute toxicity.
Respiratory, thoracic and mediastinal disorders Pulmonary - obstruction/stenosis of airway	16.7% 1/6 • Number of events 1 • Serious adverse events were collected after start of chemotherapy treatment (Day -1) through date of death (all within 6 months). Stopping Rules for excess toxicity: * Any non-hematologic grade 4 toxicity except for fevers alone * Grade III/IV GvHD or GvHD requiring more than 7 days of therapy * Hematologic toxicity: prolonged neutropenia defined as an absolute neutrophil count of less than 500 on day +35. Prolonged anemia or thrombocytopenia will not constitute toxicity.

Other adverse events

Adverse event data not reported

Additional Information

Veronika Bachanova, M.D.

Masonic Cancer Center, University of Minnesota

Phone: 612-625-5469

Email: bach0173@umn.edu

Results disclosure agreements

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