This phase I/II trial studies the side effects and best dose of modified umbilical cord blood immune cells (natural killer \[NK\] cells) combined with the antibody AFM13 (AFM13-NK) and AFM13 alone in treating patients with CD30 positive Hodgkin lymphoma or non-Hodgkin lymphoma that has come back (recurrent) or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as AFM13, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Giving AFM13 loaded with NK cells followed by AFM13 alone may kill more cancer cells and decrease cancer growth in patients with CD30 positive AFM13-NK Hodgkin and Non-Hodgkin lymphomas.
PRIMARY OBJECTIVE: I. To establish the safety and recommended phase II dose of umbilical cord blood (CB)-derived natural killer (NK) cells preloaded with the bispecific antibody AFM13 (AFM13-NK), followed by intravenous anti-CD30/CD16A monoclonal antibody AFM13 (AFM13) in patients with refractory/relapsed CD30-positive lymphoid malignancies based on incidence of dose limiting toxicities (DLTs) per dose level. (Phase I) II. To assess the activity of umbilical cord blood (CB)-derived natural killer (NK) cells preloaded with the bispecific antibody AFM13 (AFM13- NK), followed by intravenous AFM13 in patients with refractory/relapsed CD30-positive lymphoid malignancies. based on overall response rate (ORR), complete response (CR) rate and partial response (PR) rate. (Phase II) SECONDARY OBJECTIVES: I. To evaluate the duration of response. II. To evaluate the event-free survival (EFS) rate. III. To evaluate the overall survival (OS) time. IV. To quantify the persistence of infused donor CB AFM13-NK cells in the recipient. V. To conduct comprehensive immune reconstitution studies. OUTLINE: This is a dose-escalation study of AFM13-NK. Patients receive standard of care fludarabine intravenously (IV) over 1 hour and standard of care cyclophosphamide IV over 30-60 minutes on days -5 to -3, AFM13-NK IV over 4 hours on day 0, and then AFM13 IV over 4 hours on days 7, 14, and 21. After completion of study treatment, patients are followed up at 28 days, 8 weeks, 100 and 180 days and then every 3-6 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
M D Anderson Cancer Center
Houston, Texas, United States
Incidence of adverse events
Adverse events will be summarized by dose.
Time frame: Up to 2 years
Overall survival
Distribution will be estimated using Kaplan-Meier method.
Time frame: Up to 2 years
Event-free survival
Distribution will be estimated using Kaplan-Meier method.
Time frame: Up to 2 years
Overall response rate (ORR)
Will be determined by ratio of responses over number of patients with measurable lesions. Logistic regression will be used to assess the association between ORR and disease and demographic covariates of interest.
Time frame: Up to 2 years
Complete response (CR) rate
Will be determined by ratio of CRs over number of patients with measurable lesions.
Time frame: Up to 2 years
Partial response (PR) rate
Will be determined by ratio of PRs over number of patients with measurable lesions.
Time frame: Up to 2 years
Duration of response
Time frame: Time of initial response to disease relapse/progression, assessed up to 2 years
Persistence of infused donor AFM13-NK cells
Will be summarized with descriptive statistics.
Time frame: Up to 2 years
Immune reconstitution studies
Will be summarized with descriptive statistics.
Time frame: Up to 2 years
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