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Recurrent Diffuse Large B-Cell LymphomaPhase 1NCT05359211

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

A Phase 1 study testing Cyclophosphamide, Fludarabine and Lisocabtagene Maraleucel in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, run by Fred Hutchinson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cyclophosphamide, Fludarabine and Lisocabtagene Maraleucel
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
8 Dec 2022to 4 Sep 2026
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

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)

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.

Read the 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.

Being tested
Cyclophosphamide, Fludarabine, Lisocabtagene Maraleucel, Polymer-conjugated IL-15 Receptor Agonist NKTR-255, X-Ray Imaging
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • Lisocabtagene MaraleucelBiological

    Also called Anti-CD19-CAR Genetically Engineered Autologous T Lymphocytes JCAR017, Anti-CD19-CAR Genetically Engineered Autologous T-lymphocytes JCAR017, Autologous Anti-CD19-EGFRt-4-1BB-zeta-modified CAR CD8+ and CD4+ T-lymphocytes JCAR017, Breyanzi

    Given IV

  • Polymer-conjugated IL-15 Receptor Agonist NKTR-255Drug

    Also called IL-15 Receptor Agonist NKTR-255, Long-acting Polymer-conjugated IL-15, NKTR 255, NKTR-255

    Given IV

  • X-Ray ImagingProcedure or surgery

    Also called Conventional X-Ray, Diagnostic Radiology, Medical Imaging, Plain film radiographs

    Undergo x-ray imaging

  • EchocardiographyProcedure or surgery

    Also called EC

    Undergo ECHO

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, MUGA

    Undergo MUGA

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow

    Undergo bone marrow biopsy and aspiration

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow biopsy and aspiration

  • Lumbar PunctureProcedure or surgery

    Also called LP, spinal tap

    Undergo LP

  • Computed TomographyProcedure or surgery

    Also called CAT Scan, Computed Axial Tomography, CT, CT SCAN

    Undergo PET/CT

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, PET, PET scan, Positron-Emission Tomography

    Undergo PET/CT

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection

    Undergo blood and CSF sample collection

  • BiopsyProcedure or surgery

    Also called Bx

    Undergo tissue biopsy

Study groups in NCT05359211
Study groupRoleWhat they receive
Treatment (lymphodepletion, liso-cel, NKTR-255)ExperimentalPatients 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 IV over 30 minutes every 3 weeks starting on day 10 or 14 for up to 3 doses in the absence of disease progression or unacceptable toxicity. Patients undergo chest x-ray and ECHO or MUGA during screening. Patients undergo bone marrow biopsy and aspiration, LP for CSF sample collection during screening, on the study and during follow-up as clinically indicated. Patients also undergo PET/CT throughout the trial. Additionally, patients undergo blood sample collection and may optionally undergo tissue biopsy throughout the trial.
Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Lisocabtagene Maraleucel; Drug: Polymer-conjugated IL-15 Receptor Agonist NKTR-255; Procedure: X-Ray Imaging; Procedure: Echocardiography; Procedure: Multigated Acquisition Scan; Procedure: Bone Marrow Biopsy; Procedure: Bone Marrow Aspiration; Procedure: Lumbar Puncture; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Biospecimen Collection; Procedure: Biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 30 days after the last dose of NKTR-255 or until a new antitumor therapy has been initiated

  2. 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.

    Measured: Up to 21 days after the first NKTR-255 infusion

  3. 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.

    Measured: Up to 12 months after the CAR-T cell infusion

  4. 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.

    Measured: Up to 3 months after the CAR-T cell infusion

Secondary outcomes (4)

  1. 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.

    Measured: Up to 12 months after the CAR-T cell infusion

  2. 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.

    Measured: Up to 12 months after the CAR-T cell infusion

  3. 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.

    Measured: Up to 12 months after the CAR-T cell infusion

  4. 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.

    Measured: Up to 12 months after the CAR-T cell infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 May 2022
  2. Study start8 Dec 2022
  3. Primary completion4 Sep 2025
  4. Study completion4 Sep 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05359211
Sponsor's protocol ID
RG1122036
Other IDs
NCI-2022-02316, 10802
Status last verified
Sep 2026
First submitted
28 Apr 2022
Last updated
21 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cyclophosphamide, Fludarabine and Lisocabtagene Maraleucel in people with Recurrent Diffuse Large B-Cell Lymphoma and Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (AEs) (time frame: 30 days after the last dose of NKTR-255 or until a new antitumor therapy has been initiated). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05359211.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.

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