A Study of JNJ-90014496 in Participants With B-Cell Non-Hodgkin Lymphoma
- Conditions
- Lymphoma, Non-HodgkinLymphoma, B-CellLymphoma, Large B-Cell, Diffuse
- Interventions
- Registration Number
- NCT05421663
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
This is a Phase 1b/2, multicenter, open-label, study of JNJ-90014496, an autologous bi-specific chimeric antigen receptor (CAR) T-cell therapy targeting both cluster of differentiation (CD) CD19 and CD20, for the treatment of adult participants with relapsed or refractory (r/r) B-Cell non-Hodgkin lymphoma (B-NHL) or frontline high-risk diffuse large B-cell lymphoma (DLBCL).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 385
- Participant must be greater than or equal to (>=) 18 years of age, at the time of signing informed consent
- Tumor must be histologically confirmed cluster of differentiation (CD)19 and/or CD20 positive
- Must meet the following indications for each subtype in Phase 1b: Relapsed or refractory mature aggressive large B cell non-Hodgkin lymphoma (NHL) and follicular lymphoma (FL) Grade 3b: Participants must have had >= 2 lines of systemic therapy or >= 1 line of systemic therapy in case of participants ineligible for high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT); Relapsed or refractory FL Grade 1-3a and marginal zone lymphoma: Participants must have had >= 2 prior lines of anti-neoplastic systemic therapy. Participants also must have prior exposure to an anti-CD20 monoclonal antibody; Frontline high-risk diffuse large B Cell lymphoma (DLBCL): Participants must have DLBCL or high-grade B-cell lymphoma (HGBCL) with residual lymphoma by positive interim positron emission computed tomography consistent with lymphoma after 2 or 3 cycles of frontline chemoimmunotherapy. Participants must have only received 2 or 3 cycles of frontline chemoimmunotherapy for DLBCL; Phase 2 participants must have following: A diagnosis of Large B-cell lymphoma (LBCL), Follicular large B-cell lymphoma (FLBL), or transformation of indolent lymphoma; Received at least 2 prior lines of systemic therapy including an anthracycline containing chemotherapy regimen and an anti-CD20 monoclonal antibody; Relapsed or refractory disease defined as 1 or more of the following: Stable disease or Progressive disease (PD) as best response to most recent anti-lymphoma therapy OR disease progression or recurrence after a partial response (PR) or complete response (CR) to most recent anti lymphoma therapy; Cohort specific requirements:
Cohort A (CAR-T Naïve): participants who have previously not received CAR-T cell therapy for the treatment of lymphoma.
Cohort B (CAR-T Exposed): participants who have relapsed disease and prior exposure to CAR-T cell therapy for the treatment of lymphoma.
- Measurable disease as defined by Lugano 2014 classification
- Eastern cooperative oncology group (ECOG) performance status of 0 to 2
- History of symptomatic deep vein thrombosis or pulmonary embolism within six months of apheresis (line associated deep vein thrombosis is allowed)
- History of stroke, unstable angina, myocardial infarction, congestive heart failure New York Heart Association (NYHA) Class III or IV, severe cardiomyopathy or ventricular arrhythmia requiring medication or mechanical control within 6 months of apheresis
- History of a seizure disorder, dementia, cerebellar disease or neurodegenerative disorder
- Known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system
- Current active liver or biliary disease (except for Gilbert's syndrome or asymptomatic gallstones)
- Evidence of active viral or bacterial infection requiring systemic antimicrobial therapy, or uncontrolled systemic fungal infection
- Diagnosis of Human herpes virus (HHV) 8-positive DLBCL or T cell/histiocyte-rich large B-cell lymphoma or Burkitt and Burkitt-like lymphoma or Richter's transformation, Lymphomatoid granulomatosis, Plasmablastic lymphoma
- Any prior solid organ or allogeneic stem cell transplantation
- Autologous stem cell transplant within 12 weeks of apheresis; CAR-T exposed only: Prior CAR-T cell therapy within 12 weeks of apheresis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description JNJ-90014496 JNJ-90014496 Participants will receive intravenous (IV) infusion of autologous JNJ-90014496 on Day 1.
- Primary Outcome Measures
Name Time Method Phase 1b: Occurrence of Adverse Events (AEs) [Safety and Tolerability] Up to 2 Years post JNJ-90014496 infusion Occurrence of any AEs, including dose limiting toxicities (DLTs).
Phase 2: Overall Response (OR) As Assessed by Independent Review Committee (IRC) Up to 2 Years post JNJ-90014496 infusion Overall response is defined as a PR or CR at any point between the time of JNJ-90014496 infusion until PD or start of subsequent anti-lymphoma therapy, whichever occurs first (per Lugano 2014 guidelines).
- Secondary Outcome Measures
Name Time Method Phase 1b: Overall Response (OR) Up to 2 Years post JNJ-90014496 infusion Overall response is defined as a PR or CR at any point between the time of JNJ-90014496 infusion until PD or start of subsequent anti-lymphoma therapy, whichever occurs first (per Lugano 2014 guidelines).
Phase 1b: Duration of Response (DOR) Up to 2 Years post JNJ-90014496 infusion DOR is defined as the time from the first documented CR or PR after JNJ-90014496 infusion until PD or death, whichever occurs first (per Lugano 2014 guidelines).
Phase 1b: Pharmacokinetic Evaluation of JNJ-90014496 Up to 2 Years post JNJ-90014496 infusion JNJ-90014496 blood levels will be reported.
Phase 2: Occurrence of Adverse Events (AEs) by Severity Up to 2 Years post JNJ-90014496 infusion Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 as follows: Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening ), Grade 5 (Death). Cytokine release syndrome (CRS), Immune effector cell-associated neurotoxicity syndrome (ICANS), and Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading.
Phase 2: Complete Response (CR) Up to 2 Years post JNJ-90014496 infusion A CR is defined as at any point between the date of JNJ 90014496 infusion until PD or start of subsequent anti-lymphoma therapy, whichever occurs first.
Phase 2: Duration of Response (DOR) Up to 2 Years post JNJ-90014496 infusion DOR is defined as the time from the first documented CR or PR after JNJ-90014496 infusion to relapse or death, whichever occurs first.
Phase 2: Progression Free Survival (PFS) Up to 2 Years post JNJ-90014496 infusion PFS is defined as the time from the date of JNJ-90014496 infusion to the date of first documented disease progression, or death due to any cause, whichever occurs first.
Phase 2: Overall Survival (OS) Up to 2 Years post JNJ-90014496 infusion OS is defined as the time from the date of JNJ-90014496 infusion to the date of death due to any cause.
Phase 2: Maximum Observed Blood Concentration (Cmax) for JNJ-90014496 Up to 2 Years post JNJ-90014496 infusion Blood samples will be analyzed to report Cmax for JNJ-90014496.
Phase 2: Time to Reach Maximum Observed Cmax (Tmax) for JNJ-90014496 Up to 2 Years post JNJ-90014496 infusion Blood samples will be analyzed to report Tmax for JNJ-90014496.
Phase 2: Area Under the Blood Concentration Time Curve (AUC) for JNJ-90014496 Up to 2 Years post JNJ-90014496 infusion AUC for JNJ-90014496 will be reported.
Change From Baseline of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Symptom Score From Baseline Up to 18 months The FACT-Lym was developed for adult patients with lymphoma. The FACT Lym is self-administered, with a recall period for all items being the past 7 days. Responses are rated on a 5-point Likert response scale ranging from 0 "not at all" to 4 "very much". Higher scores indicate fewer symptoms and better well-being.
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Trial Locations
- Locations (30)
University of Kentucky Medical Center
🇺🇸Lexington, Kentucky, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
City of Hope
🇺🇸Duarte, California, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
University of Iowa Hospital and Clinics
🇺🇸Iowa City, Iowa, United States
Rutgers Cancer Institute of New Jersey
🇺🇸Piscataway, New Jersey, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
St. David's South Austin Medical Center
🇺🇸Austin, Texas, United States
Scroll for more (20 remaining)University of Kentucky Medical Center🇺🇸Lexington, Kentucky, United States