Non-Hodgkin LymphomaPhase 2/3NCT05664217
NKTR-255 vs Placebo Following CD19-directed CAR-T Therapy in Patients With Relapsed/Refractory Large B-cell Lymphoma
A Phase 2/3 study testing NKTR-255 at 1.5 µg/kg, NKTR-255 at 3.0 μg/kg and NKTR-255 at 3.0/6.0 μg/kg in people with Non-Hodgkin Lymphoma and Relapsed/Refractory Diffuse Large B-cell Lymphoma, run by Nektar Therapeutics at 7 sites in United States.
Trial summary
Nektar Study 18-255-01 was a Phase 2/3, randomized, double blind, placebo-controlled, multicenter study of NKTR-255 versus placebo following CD19-directed CAR-T cell therapy in patients with R/R LBCL. This study was to be run in 2 parts: Phase 2 (Stage 1) and Phase 3 (Stage 2). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Hodgkin Lymphoma, Relapsed/Refractory Diffuse Large B-cell Lymphoma
- What is being tested?
- NKTR-255 at 1.5 µg/kg, NKTR-255 at 3.0 μg/kg and NKTR-255 at 3.0/6.0 μg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 7 sitesUnited States
- Study dates
- 23 Feb 2023to 16 Aug 2024
- Phase
- Phase 2/3
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.
- Received standard of care therapy with axi-cel or liso-cel for the respective FDA (or Summary of Product Characteristics [SmPC]) approved indication(s):
- liso-cel: Patients with LBCL (including diffuse LBCL [DLBCL] not otherwise specified [including DLBCL arising from indolent lymphoma], high-grade B-cell lymphoma, primary mediastinal LBCL, and follicular lymphoma Grade 3B), who have:
- refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy;
- refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or,
- relapsed or refractory disease after two or more lines of systemic therapy.
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- axi-cel: For the treatment of adult patients with LBCL that is:
- refractory to first-line chemoimmunotherapy;
- relapses within 12 months of first-line chemoimmunotherapy; or
- R/R LBCL after 2 lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal LBLC, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
- Received lymphodepleting chemotherapy regimen according to the respective FDA (or SmPC) label for CAR-T cell therapy.
- Fluorodeoxyglucose (FDG)-avid disease on positron emission tomography (PET) imaging within 30 days prior to CAR-T cell infusion.
- FDG avid lesion(s) on PET/computed tomography (CT) scan following bridging therapy and prior to lymphodepletion, where applicable.
- Evidence of CD19 expression on any prior or current NHL tumor specimen or a high likelihood of CD19 expression based on disease histology per investigator's assessment.
- Within 7 days prior to leukapheresis, patient should have an Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
- Regarding prior systemic anti-tumor therapy:
- At least 3 months have elapsed since systemic immune checkpoint inhibitory/immune stimulatory therapy (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc).
- At least 2 weeks have elapsed since other prior systemic antitumor therapy.
- Bridging therapy (including steroids) is permitted between leukapheresis and lymphodepletion as long as Exclusion Criterion 1 is satisfied.
- Adequate organ function, defined as:
- Adequate bone marrow function (prior to lymphodepletion) for lymphodepletion chemotherapy defined as: absolute neutrophil count (ANC) ≥ 1000 cells/mm3, platelets ≥ 50,000 cells/mm3, and hemoglobin ≥ 8 g/dL in the absence of bone marrow involvement by lymphoma. No transfusion within 3 days of bone marrow function assessment; growth factor support is allowed as per institutional practice.
- Calculated creatinine clearance (Cockcroft/Gault) > 30 mL/min (Appendix 4).
- ALT and AST ≤ 3 × upper limit of normal (ULN; or < 5 × ULN for patients with lymphomatous infiltration of the liver) and total bilirubin ≤ 2 × ULN (or < 3.0 × ULN for patients with Gilbert's syndrome or lymphomatous infiltration of the liver).
- Adequate pulmonary function, oxygen saturation on room air (SaO2) ≥ 92%. Patients with a history of interstitial lung disease should undergo pulmonary function testing and must have a forced expiratory volume in 1 second (FEV1) of ≥ 50% of predicted value or diffusing capacity of the lung for carbon monoxide (DLCO; corrected) ≥ 40% of predicted value.
- Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 40% as assessed by echocardiogram (ECHO) or multiple uptake gated acquisition (MUGA) within 60 days before randomization.
- ECG demonstrating Fridericia's corrected QT interval (QTcF) < 470 ms. Patients with QTcF ≥ 470 ms will require clearance by a local cardiologist.
- Women of reproductive potential (defined as all women physiologically capable of becoming pregnant) must agree to use suitable methods of contraception from the start of study treatment until 1 month after the last dose of study drug.
- Males who have partners of reproductive potential must agree to use an effective barrier contraceptive method from the start of study treatment until 1 month after the last dose of study drug.
- Ability to understand and provide written informed consent.
- Able and willing to comply with study visit schedule and procedures, including tumor biopsy where accessible.
- Additional Eligibility Criteria Following CD19 Targeted CAR-T Cell Infusion
- Patients who have received commercially released CAR-T cell infusion must satisfy the following criteria on the day of randomization:
- No fever ≥ 38.0°C/Grade ≥ 1 CRS (American Society for Transplant and Cellular Therapy [ASTCT] criteria within 24 hours.
- No Grade ≥ 3 CRS (ASTCT criteria) within 72 hours.
- No previous Grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (ICANS) of > 72 hours duration.
- No Grade ≥ 2 ICANS (ASTCT criteria).
- No tocilizumab and/or dexamethasone within 48 hours.
- No active, serious, and/or uncontrolled infection(s).
- No other contraindication according to the Investigator's assessment.
- Patients must satisfy the following laboratory test results:
- ANC or absolute granulocyte count (AGC) ≥ 1000/μL
- Platelets ≥ 30,000/μL
- Hemoglobin ≥ 8 g/dL
- Leukocytes ≥ 3000/μL Randomization should occur no more than 1 day before the first study drug infusion.
Who cannot join
- Use of therapeutic doses of corticosteroids (≥ 5 mg/day prednisone or equivalent) or other systemic immunosuppression within 7 days prior to leukapheresis or within 72 hours prior to CAR-T cell infusion. Topical and/or inhaled steroids are permitted.
- Prior treatment with any CD19-directed CAR-T cell therapy other than the treatment planned per Inclusion Criterion 2.
- For allogeneic hematopoietic cell transplant recipients, active graft versus host disease (GVHD) and/or systemic GVHD therapy during screening or up to 30 days prior to leukapheresis.
- Known active hepatitis B (detectable hepatitis B DNA) or hepatitis C (detectable hepatitis C 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 [eg, 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.) within 1 year prior to randomization. The following are exceptions to this criterion:
- Vitiligo
- Alopecia
- Hypothyroidism (eg, 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 Investigator and with Medical Monitor approval
- History of any one of the following cardiovascular conditions within the 6 months prior to randomization: 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 Investigator 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 Investigator is a contraindication to study treatment.
- History of CNS lymphoma, primary CNS lymphoma, brain metastases, or detectable malignant cells in the cerebrospinal fluid.
- History of solid organ transplantation.
- Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Medical Monitor.
- Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter). Dedicated central venous access catheters such as a Port-a-Cath or Hickman catheter are permitted.
- Active or current participation on any other interventional studies.
- Use of an investigational agent or an investigational device within 28 days of CAR-T cell therapy.
- Live, attenuated vaccines are prohibited within 30 days of randomization.
- Any condition including medical, emotional, psychiatric, or logistical that, in the opinion of the Investigator, would preclude the patient from adhering to the protocol or would increase the risk associated with study participation or study drug administration or interfere with the interpretation of results.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Novant Health Cancer Institute
Charlotte, North Carolina, 28204
Oncology Hematology Care Inc - Cincinnati
Cincinnati, Ohio, 45236
University of Kansas Cancer Center
Fairway, Kansas, 66205
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
NYU Langone Medical Center
New York, New York, 10016
Washington University School of Medicine in St. Louis
St Louis, Missouri, 63110
UMass Memorial Medical Center
Worcester, Massachusetts, 01655
About this study
Official title: A Phase 2/3, Randomized, Double Blind, Placebo-controlled, Multicenter Study of NKTR-255 vs Placebo Following CD19-directed CAR-T Cell Therapy in Patients With Relapsed/Refractory Large B-cell Lymphoma
Nektar Study 18-255-01 was a Phase 2/3, randomized, double blind, placebo-controlled, multicenter study of NKTR-255 versus placebo following CD19-directed CAR-T cell therapy in patients with R/R LBCL. This study was to be run in 2 parts: Phase 2 (Stage 1) and Phase 3 (Stage 2).
This study evaluated the safety and efficacy of NKTR-255 following CD19-directed chimeric antigen (CAR)-T cell therapy in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL).
NKTR-255 was 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. Chimeric antigen (CAR)-T cell product 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 following the treatment with CD19 CAR-T cell therapy may work better in treating large B-cell lymphoma than either drug alone.
Read the detailed description
Patients were treated with lymphodepletion chemotherapy (as recommended by the CAR-T cell manufacturer) and soon after received a one-time CD19-directed CAR-T cell infusion (as per product label). Study drug (NKTR-255 or placebo) was administered intravenously approximately 14 days after CAR-T cell infusion and administered every 3 weeks for up to 7 cycles or 5 months (whichever was earlier) in the absence of disease progression or unacceptable toxicity.
During Stage 1, Nektar made the decision to close the study at all sites.
- Being tested
- NKTR-255 at 1.5 µg/kg, NKTR-255 at 3.0 μg/kg, NKTR-255 at 3.0/6.0 μg/kg, Placebo Comparator
- Keywords
- NHL, LBCL, DLBCL, CAR, CAR-T, cell therapy, NKTR-255, chimeric antigen receptor, autologous T-cell, axi-cel, liso-cel, immunotherapy, B-cell malignancies
- Medical subject headings
- Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NKTR-255 at 1.5 µg/kgDrug
Also called Polymer-conjugated interleukin (IL)-15 Receptor Agonist
NKTR-255 at 1.5 µg/kg
NKTR-255 at 3.0 μg/kgDrug
Also called Polymer-conjugated interleukin (IL)-15 Receptor Agonist
NKTR-255 at 3.0 μg/kg
NKTR-255 at 3.0/6.0 μg/kgDrug
Also called Polymer-conjugated interleukin (IL)-15 Receptor Agonist
NKTR-255 at 3.0/6.0 μg/kg
Placebo ComparatorOther
Commercially available 0.9% Sodium Chloride Solution for Injection (USP)
| Study group | Role | What they receive |
|---|---|---|
| Stage 1 NKTR-255 at 1.5 µg/kg | Experimental | In this arm of Stage 1 (Phase 2 of the study), NKTR-255 was dosed at 1.5 µg/kg. NKTR-255 was administered intravenously approximately 14 days after CD19-directed CAR-T cell infusion.
Patients were dosed every 3 weeks for up to 7 cycles or 5 months, whichever was earlier, in the absence of disease progression or unacceptable toxicity. Receives: Drug: NKTR-255 at 1.5 µg/kg |
| Stage 1 NKTR-255 at 3.0 μg/kg | Experimental | In this arm of Stage 1 (Phase 2 of the study), NKTR-255 was dosed at 3.0 μg/kg. NKTR-255 was administered intravenously approximately 14 days after CD19-directed CAR-T cell infusion.
Patients were dosed every 3 weeks for up to 7 cycles or 5 months, whichever was earlier, in the absence of disease progression or unacceptable toxicity. Receives: Drug: NKTR-255 at 3.0 μg/kg |
| Stage 1 NKTR-255 at 3.0/6.0 μg/kg | Experimental | In this arm of Stage 1 (Phase 2 of the study), patients were dosed with 3.0 μg/kg NKTR-255 in Cycle 1 (C1) and continue in Cycle 2 and subsequent cycles (C+) with 6.0 μg/kg NKTR-255 (hereinafter referred to as 3.0/6.0 µg/kg NKTR-255).
NKTR-255 was administered intravenously approximately 14 days after CD19-directed CAR-T cell infusion.
Patients were dosed every 3 weeks for up to 7 cycles or 5 months, whichever was earlier, in the absence of disease progression or unacceptable toxicity. Receives: Drug: NKTR-255 at 3.0/6.0 μg/kg |
| Placebo | Placebo comparator | Placebo was commercially available 0.9% Sodium Chloride Solution for Injection (USP). Placebo was administered intravenously approximately 14 days after CD19-directed CAR-T cell infusion. Placebo was infused every 3 weeks for up to 7 cycles or 5 months, whichever was earlier. Receives: Other: Placebo Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response (CR) Rate
The incidence of complete response by the Lugano Classification (Cheson et al, 2014) as determined by blinded independent central review (BICR)
Measured: At month 6
Secondary outcomes (10)
Number of Patients With at Least One (1) Treatment-emergent Adverse Events (AEs)
Measured: From the first dose of study drug up to 30 days after the last dose of study drug, average of 1 year
Complete Response (CR) Rate
The incidence of complete response at month 3 by the Lugano Classification (Cheson et al, 2014) as determined by blinded independent central review (BICR)
Measured: At month 3
Best Overall Complete Response (CR) Rate
The incidence of complete response in study by the Lugano Classification (Cheson et al, 2014) as determined by blinded independent central review (BICR)
Measured: Approximately 1 year and 5.5 months
Objective Response Rate (ORR)
The incidence of objective response rate is defined as the incidence of either a complete response or a partial response by the Lugano Classification (Cheson et al, 2014) as determined by BICR
Measured: At month 3
Objective Response Rate (ORR)
The incidence of objective response rate is defined as the incidence of either a complete response or a partial response by the Lugano Classification (Cheson et al, 2014) as determined by BICR
Measured: At month 6
Best Overall Objective Response Rate (ORR)
The incidence of objective response rate in study is defined as the incidence of either a complete response or a partial response by the Lugano Classification (Cheson et al, 2014) as determined by BICR
Measured: Approximately 1 year and 5.5 months
Duration of Response (DOR)
The duration of response is derived only among subjects who experience an objective response per Lugano Classification (Cheson et al, 2014) as determined by blinded central review and is defined as the time from first response to disease progression per the Lugano Classification or death from any cause
Measured: Approximately 1 year and 5.5 months
Overall Duration of Progression-Free Survival (PFS)
Progression Free Survival is defined as the time from randomization to disease progression per Lugano Classification (Cheson et al, 2014) or death from any cause
Measured: Approximately 1 year and 5.5 months
Overall Survival (OS)
Overall survival is defined as the time from randomization to death from any cause
Measured: Approximately 1 year and 5.5 months
Event-free Survival (EFS)
Event-free survival is defined as the time from randomization to the earliest date of disease progression by the Lugano Classification (Cheson et al, 2014) as determined by BICR, commencement of new lymphoma therapy, or death from any cause.
Measured: At 3, 6 and 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2022
- Study start23 Feb 2023
- Primary completion22 May 2024
- Study completion16 Aug 2024
Why it stopped: Sponsor decided to end the study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Hodgkin LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- This study was to be run in 2 parts: Phase 2 (Stage 1) and Phase 3 (Stage 2). However, during Stage 1, Nektar made the decision to close the study at all sites. Routine safety monitoring was conducted by the Data Monitoring Committee (DMC) on a regular basis.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nektar Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Nektar Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05664217
- Sponsor's protocol ID
- 18-255-01
- Status last verified
- Sep 2026
- First submitted
- 1 Dec 2022
- Last updated
- 16 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No