NCT05359211

NKTR-255 in Combination With CAR-T Cell Therapy for the Treatment of Relapsed or Refractory Large B-cell Lymphoma

A Phase Ib Open-Label Study Evaluating the Safety and Efficacy of NKTR-255 in Combination With CD19-Directed CAR-T Cell Therapy in Patients With Relapsed/Refractory (R/R) Large B-Cell Lymphoma (LBCL)

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Recurrent Diffuse Large B-Cell Lymphoma
• Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• Recurrent Grade 3b Follicular Lymphoma
• Recurrent Primary Mediastinal Large B-Cell Lymphoma
• Refractory Diffuse Large B-Cell Lymphoma
• Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• Refractory Grade 3b Follicular Lymphoma
• Refractory Primary Mediastinal Large B-Cell Lymphoma
• Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma

Interventions

Type	Name	Description
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine	Given IV
BIOLOGICAL	Lisocabtagene Maraleucel	Given IV
DRUG	Polymer-conjugated IL-15 Receptor Agonist NKTR-255	Given IV
PROCEDURE	X-Ray Imaging	Undergo x-ray imaging
PROCEDURE	Echocardiography	Undergo ECHO
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow biopsy and aspiration
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow biopsy and aspiration
PROCEDURE	Lumbar Puncture	Undergo LP
PROCEDURE	Computed Tomography	Undergo PET/CT
PROCEDURE	Positron Emission Tomography	Undergo PET/CT
PROCEDURE	Biospecimen Collection	Undergo blood and CSF sample collection
PROCEDURE	Biopsy	Undergo tissue biopsy

Timeline

• Start date: 2022-12-08
• Primary completion: 2025-09-04
• Completion: 2026-09-04
• First posted: 2022-05-03
• Last updated: 2026-03-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study