Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin
Conditions
Keywords
CD20/CD19
Brief summary
This is a Phase 1b/2, multicenter, open-label, study of JNJ-90014496, an autologous dual targeting chimeric antigen receptor (CAR) T-cell therapy targeting both cluster of differentiation (CD) CD20 and CD19, 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).
Interventions
BIOLOGICALJNJ-90014496
JNJ-90014496, an autologous dual targeting chimeric antigen receptor (CAR) - T cell therapy targeting Cluster of differentiation (CD)20 and CD19.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 indications for each subtype in Phase 1b as specified in protocol and Phase 2 participants must have following: Diagnosis of Large B-cell lymphoma (LBCL), Follicular large B-cell lymphoma (FLBCL), or transformation of indolent lymphoma; Received at least 2 prior lines of systemic therapy; 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 as mentioned in protocol * Measurable disease as defined by Lugano 2014 classification * Eastern cooperative oncology group (ECOG) performance status of 0 to 2
Exclusion criteria
* 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 high-grade B-cell lymphoma with 11q aberrations (previously Burkitt-like lymphoma) or Richter's transformation or Lymphomatoid granulomatosis or Plasmablastic lymphoma or Waldenstrom's Macroglobulinemia * Any prior solid organ or allogeneic stem cell transplantation * Autologous stem cell transplant within 12 weeks of apheresis; Prior CAR-T cell therapy within 12 weeks of apheresis
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Occurrence of Adverse Events (AEs) [Safety and Tolerability] | Up to 15 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 6 months post last participant's 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
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Pharmacokinetic Evaluation of JNJ-90014496 | Up to 6 months post last participant's JNJ-90014496 infusion | JNJ-90014496 blood levels will be reported. |
| Phase 2: Occurrence of Adverse Events (AEs) by Severity | Up to 15 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 6 months post last participant's 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 6 months post last participant's 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 6 months post last participant's 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 15 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 6 months post last participant's 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 6 months post last participant's 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 6 months post last participant's JNJ-90014496 infusion | AUC for JNJ-90014496 will be reported. |
| Phase 1b: Duration of Response (DOR) | Up to 6 months post last participant's 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). |
| Change From Baseline of the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Symptom Score | From Baseline Up to 6 months post JNJ-90014496 infusion | 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. |
| Phase 1b: Overall Response (OR) | Up to 6 months post last participant's 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). |
Countries
Australia, Canada, Denmark, Netherlands, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed