This phase Ib trial studies the effects of NKTR-255 in combination with chimeric antigen (CAR)-T cell therapy and to see how well they work in treating patients with large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). NKTR-255 is an investigational IL-15 receptor agonist designed to boost the immune system's natural ability to fight cancer. T cells are infection fighting blood cells that can kill tumor cells. Lisocabtagene maraleucel is a CAR-T cell product that consists of genetically engineered T cells, modified to recognize CD19, a protein on the surface of cancer cells. These CD19-specific T cells may help the body's immune system identify and kill CD19-positive cancer cells. Giving NKTR-255 together with lisocabtagene maraleucel may work better in treating large B-cell lymphoma than either drug alone.
OUTLINE: Patients receive standard of care lymphodepletion therapy consisting of cyclophosphamide and fludarabine on days -5 to -3 followed by liso-cel CAR-T cell infusion on day 0. Patients then receive NKTR-255 intravenously (IV) over 30 minutes every 3 weeks starting on day 10 or 14 in the absence of disease progression or unacceptable toxicity. Patients undergo chest x-ray and echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening. Patients undergo bone marrow biopsy and aspiration, lumbar puncture (LP) for cerebrospinal fluid (CSF) sample collection during screening, on the study and during follow-up as clinically indicated. Patients also undergo positron emission tomography (PET)/computed tomography (CT) throughout the trial. Additionally, patients undergo blood sample collection and may optionally undergo tissue biopsy throughout the trial. After completion of study treatment, patients are followed up every 30 days then every 3 months up to 12 months after the CAR-T cell infusion.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Given IV
Given IV
Given IV
Undergo x-ray imaging
Undergo ECHO
Undergo MUGA
Undergo bone marrow biopsy and aspiration
Undergo bone marrow biopsy and aspiration
Undergo LP
Undergo PET/CT
Undergo PET/CT
Undergo blood and CSF sample collection
Undergo tissue biopsy
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Incidence of adverse events (AEs)
Grade ≥ 3 AEs considered related to NKTR-255 will be listed and summarized. Summaries of grade ≥ 3 laboratory data will include, at a minimum, treatment-emergent laboratory abnormalities. Summaries of AEs and laboratory abnormalities will be based on the safety evaluable population.
Time frame: 30 days after the last dose of NKTR-255 or until a new antitumor therapy has been initiated
Dose-limiting toxicity (DLT) rates
Observed DLT rates will be summarized based on the DLT evaluable population. Final DLT rates at each dose level will be estimated by isotonic regression by applying the pooled adjacent violators algorithm.
Time frame: Up to 21 days after the first NKTR-255 infusion
Optimal biological dose (OBD)
A composite of clinical information will be utilized to determine the OBD based on safety and tolerability, confirmation of maximum target engagement, optimal biological effects without undesirable clinical effects, pharmacokinetic parameters, and biological response data.
Time frame: Up to 12 months after the CAR-T cell infusion
Complete response (CR) rate
The CR rate will be summarized along with the 2-sided 95% exact Clopper-Pearson confidence interval based on the efficacy evaluable population.
Time frame: Up to 3 months after the CAR-T cell infusion
Complete response (CR) and overall response (OR) rates
The CR and OR rates will be summarized along with the 2-sided 95% exact Clopper-Pearson confidence interval based on the efficacy evaluable population.
Time frame: Up to 12 months after the CAR-T cell infusion
Duration of response (DOR)
Will be assessed among responders. If a patient does not have an event for the DOR analyses, the patient will be censored at the date of the last adequate disease assessments or prior to the earliest censoring event. The censoring reason can include last contact/follow-up, discontinuation or completion of the study, receipt of another anticancer treatment with the exception of consolidation therapy with hematopoietic cell transplantation (HCT), and at least two consecutive missed scheduled disease assessments. Kaplan-Meier (KM) method will be used to analyze DOR.
Time frame: Up to 12 months after the CAR-T cell infusion
Progression free survival (PFS)
Will be assessed among responders. If a patient does not have an event for the PFS analyses, the patient will be censored at the date of the last adequate disease assessments or prior to the earliest censoring event. The censoring reason can include last contact/follow-up, discontinuation or completion of the study, receipt of another anticancer treatment with the exception of consolidation therapy with HCT, and at least two consecutive missed scheduled disease assessments. KM method will be used to analyze PFS.
Time frame: Up to 12 months after the CAR-T cell infusion
Overall survival (OS)
Analyses of OS will be performed in the safety population. For assessment of OS, data from surviving patients will be censored at the last time that the patient is known to be alive. KM method will be used to analyze OS.
Time frame: Up to 12 months after the CAR-T cell infusion
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