ACTIVE_NOT_RECRUITING

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

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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)

Quick Facts

Study Start:2022-12-08

Study Completion:2026-09-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05359211

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Male or female \>= 18 years of age at the time of consent * Patients with LBCL (including diffuse large B-cell lymphoma \[DLBCL\] not otherwise specified \[including DLBCL arising from indolent lymphoma\], high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B) with a Food and Drug Administration (FDA)-approved indication for treatment with liso-cel * Fludeoxyglucose F-18 (FDG)-avid disease on positron emission tomography (PET) imaging or pathology evidence of active disease * Evidence of CD19 expression on any prior or current tumor specimen or a high likelihood of CD19 expression based on disease histology * Karnofsky performance status \>= 60% * Absolute neutrophil count (ANC) \>= 1000 cells/mm\^3 in the absence of bone marrow involvement by lymphoma * Platelets \>= 50,000 cells/mm\^3 in the absence of bone marrow involvement by lymphoma * Hemoglobin \>= 8 g/dL in the absence of bone marrow involvement by lymphoma * Calculated creatinine clearance (Cockcroft/Gault) \> 30 mL/min/1.73 m\^2 * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN (or \< 5 x ULN for subjects with lymphomatous infiltration of the liver) * Total bilirubin =\< 2 (or \< 3.0 for subjects with Gilbert's syndrome or lymphomatous infiltration of the liver) * Common Terminology Criteria for Adverse Events (CTCAE) Grade =\< 1 dyspnea * Saturation of oxygen (Sa02) \>= 92% on room air * Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing and must have a forced expiratory volume in 1 second (FEV1) of \>= 50% of predicted value * Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing and must have a diffusing capacity of the lung for carbon monoxide (DLCO; corrected) \>= 40% of predicted value * Left ventricular ejection fraction (LVEF) \>= 40% as assessed by echocardiogram or multiple uptake gated acquisition (MUGA) * Patients with Fridericia's corrected QT interval (QTcF) \> 450 ms for men and \> 470 ms for women will require clearance by a cardiologist * Women of reproductive potential (defined as all women physiologically capable of becoming pregnant) must agree to use suitable methods of contraception for 1 month after the last dose of study therapy (NKTR-255) * Males who have partners of reproductive potential must agree to use an effective barrier contraceptive method for 1 month after the last dose of study therapy (NKTR-255) * Ability to understand and provide informed consent * Able and willing to comply with study visit schedule and procedures, including tumor biopsy where feasible and with acceptable risk	* Planned use of therapeutic doses of corticosteroids (\> 20 mg/day prednisone or equivalent) or other systemic immunosuppression within 7 days prior to leukapheresis or within 72 hours prior to liso-cel infusion. Topical and/or inhaled steroids are permitted * Prior treatment with any CD19 CAR-T cell therapy * For allogeneic hematopoietic cell transplant (HCT) recipients, active graft versus host disease (GVHD) and/or systemic GVHD therapy within 30 days prior to planned leukapheresis * Known active hepatitis B (detectable hepatitis B deoxyribonucleic acid \[DNA\]) or hepatitis C (detectable hepatitis C ribonucleic acid \[RNA\]) * Known human immunodeficiency virus (HIV) infection * Pregnant or breastfeeding women * Prior treatment with any IL-2 or IL-15 agonist and/or biosimilar agents * Active autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., ulcerative colitis, Crohn's disease\], celiac disease, or other serious chronic gastrointestinal conditions associated with diarrhea, autoimmune vasculitis, systemic lupus erythematosus, Wegener syndrome \[granulomatosis with polyangiitis\], myasthenia gravis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.) requiring immunosuppressive therapy. The following are exceptions to this criterion: * Vitiligo. * Alopecia. * Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement. * Type 1 diabetes mellitus. * Psoriasis not requiring systemic treatment. * Conditions considered to be low risk of serious deterioration by the principal investigator (PI). * History of any one of the following cardiovascular conditions within the past 6 months: class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, or unstable angina; unless clearance by a cardiologist is obtained. History of other clinically significant cardiac disease that, in the opinion of the PI or designee, is a contraindication to study treatment is also excluded * History or presence of clinically relevant central nervous system (CNS) pathology, such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, or psychosis that in the opinion of the PI is a contraindication to study treatment. * Patients with active parenchymal CNS involvement by malignancy will be excluded. Patients with prior or current secondary leptomeningeal CNS disease are eligible. CNS disease prophylaxis must be stopped at least 1 week prior to liso-cel infusion * History of solid organ transplantation * Active, serious, and uncontrolled infection(s)

Inclusion Criteria

Exclusion Criteria

* Male or female \>= 18 years of age at the time of consent
* Patients with LBCL (including diffuse large B-cell lymphoma \[DLBCL\] not otherwise specified \[including DLBCL arising from indolent lymphoma\], high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B) with a Food and Drug Administration (FDA)-approved indication for treatment with liso-cel
* Fludeoxyglucose F-18 (FDG)-avid disease on positron emission tomography (PET) imaging or pathology evidence of active disease
* Evidence of CD19 expression on any prior or current tumor specimen or a high likelihood of CD19 expression based on disease histology
* Karnofsky performance status \>= 60%
* Absolute neutrophil count (ANC) \>= 1000 cells/mm\^3 in the absence of bone marrow involvement by lymphoma
* Platelets \>= 50,000 cells/mm\^3 in the absence of bone marrow involvement by lymphoma
* Hemoglobin \>= 8 g/dL in the absence of bone marrow involvement by lymphoma
* Calculated creatinine clearance (Cockcroft/Gault) \> 30 mL/min/1.73 m\^2
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x ULN (or \< 5 x ULN for subjects with lymphomatous infiltration of the liver)
* Total bilirubin =\< 2 (or \< 3.0 for subjects with Gilbert's syndrome or lymphomatous infiltration of the liver)
* Common Terminology Criteria for Adverse Events (CTCAE) Grade =\< 1 dyspnea
* Saturation of oxygen (Sa02) \>= 92% on room air
* Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing and must have a forced expiratory volume in 1 second (FEV1) of \>= 50% of predicted value
* Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing and must have a diffusing capacity of the lung for carbon monoxide (DLCO; corrected) \>= 40% of predicted value
* Left ventricular ejection fraction (LVEF) \>= 40% as assessed by echocardiogram or multiple uptake gated acquisition (MUGA)
* Patients with Fridericia's corrected QT interval (QTcF) \> 450 ms for men and \> 470 ms for women will require clearance by a cardiologist
* Women of reproductive potential (defined as all women physiologically capable of becoming pregnant) must agree to use suitable methods of contraception for 1 month after the last dose of study therapy (NKTR-255)
* Males who have partners of reproductive potential must agree to use an effective barrier contraceptive method for 1 month after the last dose of study therapy (NKTR-255)
* Ability to understand and provide informed consent
* Able and willing to comply with study visit schedule and procedures, including tumor biopsy where feasible and with acceptable risk

* Planned use of therapeutic doses of corticosteroids (\> 20 mg/day prednisone or equivalent) or other systemic immunosuppression within 7 days prior to leukapheresis or within 72 hours prior to liso-cel infusion. Topical and/or inhaled steroids are permitted
* Prior treatment with any CD19 CAR-T cell therapy
* For allogeneic hematopoietic cell transplant (HCT) recipients, active graft versus host disease (GVHD) and/or systemic GVHD therapy within 30 days prior to planned leukapheresis
* Known active hepatitis B (detectable hepatitis B deoxyribonucleic acid \[DNA\]) or hepatitis C (detectable hepatitis C ribonucleic acid \[RNA\])
* Known human immunodeficiency virus (HIV) infection
* Pregnant or breastfeeding women
* Prior treatment with any IL-2 or IL-15 agonist and/or biosimilar agents
* Active autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., ulcerative colitis, Crohn's disease\], celiac disease, or other serious chronic gastrointestinal conditions associated with diarrhea, autoimmune vasculitis, systemic lupus erythematosus, Wegener syndrome \[granulomatosis with polyangiitis\], myasthenia gravis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.) requiring immunosuppressive therapy. The following are exceptions to this criterion:
* Vitiligo.
* Alopecia.
* Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
* Type 1 diabetes mellitus.
* Psoriasis not requiring systemic treatment.
* Conditions considered to be low risk of serious deterioration by the principal investigator (PI).
* History of any one of the following cardiovascular conditions within the past 6 months: class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, or unstable angina; unless clearance by a cardiologist is obtained. History of other clinically significant cardiac disease that, in the opinion of the PI or designee, is a contraindication to study treatment is also excluded
* History or presence of clinically relevant central nervous system (CNS) pathology, such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, or psychosis that in the opinion of the PI is a contraindication to study treatment.
* Patients with active parenchymal CNS involvement by malignancy will be excluded. Patients with prior or current secondary leptomeningeal CNS disease are eligible. CNS disease prophylaxis must be stopped at least 1 week prior to liso-cel infusion
* History of solid organ transplantation
* Active, serious, and uncontrolled infection(s)

Contacts and Locations

Principal Investigator

Alexandre Hirayama

PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Study Locations (Sites)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: Fred Hutchinson Cancer Center

Alexandre Hirayama, PRINCIPAL_INVESTIGATOR, Fred Hutch/University of Washington Cancer Consortium

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-12-08

Study Completion Date2026-09-04

Study Record Updates

Study Start Date2022-12-08

Study Completion Date2026-09-04

Terms related to this study

Additional Relevant MeSH Terms

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