CAR-T Therapy for Non-Hodgkin's Lymphoma
Recruiting in Palo Alto (17 mi)
+27 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Janssen Research & Development, LLC
Must be taking: Anti-CD20 antibody
Disqualifiers: Organ transplant, Stroke, Heart failure, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial tests a new treatment where a patient's own immune cells are modified to better attack their cancer. It is for adults with a type of lymphoma that hasn't responded to other treatments. The modified cells target specific proteins on the cancer cells to help the immune system destroy them. This new method enhances the patient's immune cells to find and eliminate cancer cells.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the treatment C-CAR039 for Non-Hodgkin's Lymphoma?
The effectiveness of C-CAR039, a CAR-T therapy, can be indirectly supported by studies on similar treatments like axicabtagene ciloleucel and tisagenlecleucel, which have shown promising results in treating relapsed or refractory large B-cell lymphoma, a type of Non-Hodgkin's Lymphoma. These therapies have demonstrated durable responses in patients who had limited options, suggesting potential benefits for C-CAR039 as well.
12345What safety data exists for CAR-T therapy in humans?
CAR T-cell therapies, like those targeting CD19 for non-Hodgkin lymphoma, can cause side effects such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which may affect the brain and nervous system. These side effects are known complications and require careful management.
678910What makes the treatment C-CAR039 unique for Non-Hodgkin's Lymphoma?
C-CAR039 is a novel CAR-T cell therapy that targets both CD19 and CD20 proteins on B-cells, unlike other CAR-T therapies that typically target only CD19. This dual targeting may enhance its effectiveness in treating Non-Hodgkin's Lymphoma by potentially overcoming resistance seen in single-target therapies.
111121314Eligibility Criteria
Adults with B-Cell non-Hodgkin lymphoma that has come back or didn't respond after at least two standard treatments can join. They must be over 18, have a certain level of physical fitness (ECOG status 0 or 1), and their major organs need to function well. People with recent serious blood clots, active severe infections, other cancers within the last five years (except some skin or in situ cancers), pregnant women, and those with certain heart conditions cannot participate.Inclusion Criteria
I am fully active or restricted in physically strenuous activity but can do light work.
My tumor is confirmed to be CD19 or CD20 positive.
I am 18 years old or older.
+3 more
Exclusion Criteria
I had a blood clot in my leg or lung in the last 6 months.
I had a stem cell transplant less than 12 weeks before my CAR T cell treatment.
I have been diagnosed with a specific type of lymphoma linked to the HHV-8 virus.
+6 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive an intravenous infusion of autologous JNJ-90014496 on Day 1
1 day
1 visit (in-person)
Follow-up
Participants are monitored for safety, effectiveness, and pharmacokinetics after treatment
24 months
Long-term follow-up
Participants are monitored for overall survival and progression-free survival
3 years
Participant Groups
The trial is testing JNJ-90014496, an experimental CAR T-cell therapy targeting CD19 and CD20 proteins on cancer cells. It's for adults whose aggressive B-cell non-Hodgkin lymphoma hasn't been cured by previous treatments. This Phase Ib study is open-label, meaning everyone knows they're getting the test treatment.
1Treatment groups
Experimental Treatment
Group I: JNJ-90014496Experimental Treatment1 Intervention
Participants will receive intravenous (IV) infusion of autologous JNJ-90014496 on Day 1.
C-CAR039 is already approved in United States, China for the following indications:
🇺🇸 Approved in United States as C-CAR039 for:
- Relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL)
- Follicular lymphoma
🇨🇳 Approved in China as C-CAR039 for:
- Relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Pittsburgh Medical CenterPittsburgh, PA
Swedish Cancer InstituteSeattle, WA
Texas Transplant InstituteSan Antonio, TX
Princess Margaret Cancer Centre University Health NetworkToronto, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
Janssen Research & Development, LLCLead Sponsor
Cellular Biomedicine Group Ltd.Lead Sponsor
Cellular Biomedicine Group, Inc.Lead Sponsor
City of Hope Medical CenterCollaborator
References
Long-term outcomes of relmacabtagene autoleucel in Chinese patients with relapsed/refractory large B-cell lymphoma: Updated results of the RELIANCE study. [2023]The RELIANCE study has demonstrated the activity and safety of relmacabtagene autoleucel (relma-cel) (JW Therapeutics [Shanghai] Co, Ltd, Shanghai, China), a CD19-targeted chimeric antigen receptor T-cell product, in patients with heavily pre-treated relapsed/refractory large B-cell lymphoma (r/r LBCL). This study aimed to report the updated 2-year data of the RELIANCE study.
Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. [2022]Most patients with advanced-stage indolent non-Hodgkin lymphoma have multiple relapses. We assessed axicabtagene ciloleucel autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in relapsed or refractory indolent non-Hodgkin lymphoma.
Value in Using CAR T Cells for DLBCL. [2019]The phase II JULIET trial suggests that the CD19-targeting CAR T-cell therapy tisagenlecleucel produces durable responses in patients with relapsed and refractory diffuse large B-cell lymphoma. Three months after the therapy, 32% of the patients showed complete responses and 6% showed partial responses. After 6 months, those rates were 30% and 7%.
Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. [2022]Currently, three chimeric antigen receptor (CAR)-T cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel have been approved by the U.S. Food and Drug Administration for the treatment of large B cell lymphoma, which provide a novel and promising choice for patients with relapsed or refractory to traditional anti-tumor treatments. Thus, it is pertinent to describe the efficacy and safety profile of the three products available by summarizing the current evidence.
CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. [2020]Adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T cell has changed the treatment landscape of B-cell non-Hodgkin's lymphoma (NHL), especially for aggressive B-cell lymphomas. Single-center and multicenter clinical trials with anti-CD19 CAR T-cell therapy have shown great activity and long-term remissions in poor-risk diffuse large B-cell lymphoma (DLBCL) when no other effective treatment options are available. Two CAR T-cell products [axicabtagene ciloleucel (axi-cel) and tisagenlecleucel] have obtained US Food and Drug Administration approval for the treatment of refractory DLBCL after two lines of therapy. A third product, liso-cel, is currently being evaluated in clinical trials and preliminary results appear very promising. CAR T-cell-related toxicity with cytokine-release syndrome and neurotoxicity remain important potential complications of this therapy. Here, we review the s biology, structure, clinical trial results and toxicity of two commercially approved CAR T-cell products and others currently being studied in multicenter clinical trials in B-cell NHLs.
Irinotecan plus carboplatin for patients with carcinoma of unknown primary site. [2023]Carcinoma of unknown primary site (CUP) is rarely encountered in clinical practice and optimal chemotherapy has not yet been established. This phase II study was conducted to evaluate the efficacy and toxicity of combined irinotecan+carboplatin therapy in chemotherapy-naive patients with CUP. Irinotecan was administered at 60 mg m(-2) as a 90-min intravenous infusion on days 1, 8 and 15. Carboplatin was administered at an area-under-the curve of 5 mg ml(-1) min as a 60-min intravenous infusion on day 1. This cycle was repeated every 28 days for up to six cycles. Forty-five patients were enrolled in the study. An intent-to-treat analysis revealed an objective response rate to the treatment of 41.9% (95% confidence interval, 27.0-57.9%). The median time to progression was 4.8 months and the median survival was 12.2 months. The 1- and 2-year survival rates were 44 and 27%, respectively. The most frequent grade 3 or more severe adverse events were leukopaenia (21%), neutropaenia (33%), anaemia (25%) and thrombocytopaenia (20%). Thus, the combination of irinotecan plus carboplatin was found to be active in patients with CUP. Therefore, the regimen may be one of the potentially available chemotherapeutic options for community standard of care in patients with a good performance status.
CAR T-Cell-Associated Neurotoxicity: Current Management and Emerging Treatment Strategies. [2021]Axicabtagene ciloleucel and tisagenlecleucel are 2 chimeric antigen receptor (CAR) T-cell immunotherapies targeting CD19 for the treatment of B-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma. Two commonly recognized complications associated with CAR T-cell therapies are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS can occur in isolation or concomitantly with CRS following CAR T-cell therapy and may be due to disruption of the blood-brain barrier and the effects of elevated cytokine levels on the central nervous system. Presently, the optimum management of ICANS remains elusive, as there lacks consensus guidelines. The objective of this review is to provide a comprehensive summary of ICANS and strategies for prompt identification and management of patients presenting to the intensive care unit with this syndrome.
Phase II study of weekly irinotecan and carboplatin for refractory or relapsed small-cell lung cancer. [2019]We designed a phase II study of weekly irinotecan (CPT-11) and carboplatin for refractory or relapsed small cell lung cancer (SCLC) and assessed the response rate, survival, and toxicity. Twenty-nine patients with refractory or relapsed SCLC were entered onto the trial. The median time off chemotherapy was 3.5 months (range: 0.8-12.9). Patients were treated at 4-week intervals using CPT-11 (50 mg/m(2) intravenously on days 1, 8 and 15) plus carboplatin (AUC = 2 mg/ml min, intravenously on days 1, 8, 15). All patients were assessable for toxicity and survival; 28 patients were assessable for response. There were nine partial responses (PRs). Overall response rate was 31.0% (95% CI: 15.3-50.8%). The median time to progression was 3.5 months. Median survival time was 6.1 months. Major toxicity was myelosuppression. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 52 and 21% of patients, respectively. Grade 3-4 diarrhea was observed in 7%. There was one treatment-related death due to febrile neutropenia and sepsis. This combination of CPT-11 and carboplatin seems to be active second-line regimen with acceptable toxicity against small cell lung cancer.
Combination of irinotecan and platinum for platinum-resistant or refractory recurrent ovarian cancers: A preliminary case series. [2020]Non-platinum single agents are usually used for patients with platinum-resistant recurrent ovarian cancers (ROC). However, the efficacy of these drugs is limited. The aim of the present study was to evaluate the efficacy and adverse events (AE) of combination therapy with irinotecan and platinum (CPT-Pt) for ROC. A total of 28 platinum-resistant or refractory patients with ROC treated with CPT-Pt at the National Defense Medical College Hospital institution between 2002 and 2012 were identified. All patients received taxane and carboplatin (TC) as a first-line treatment and relapsed within 6 months after completion of TC, or progressed during TC therapy. The median age was 59 years (range, 16-78), and median number of CPT-Pt therapy cycles was 5.5 (range, 2-16). The overall response rate was 14%, with a complete response (CR) in 2 patients and partial response (PR) in 2 patients. Stable disease (SD) for >3 months was observed in 15 patients (54%), resulting in a clinical benefit rate (CBR = CR + PR + SD) of 68%. The median progression-free survival and overall survival were 8 and 15 months, respectively. Fifteen cases (68%) developed grade 3/4 hematological AE and 3 cases (11%) developed non-hematological grade 3/4 AE, which were resolved by conservative management or dose reduction. Platinum re-treatment with irinotecan for platinum refractory or resistant ROC may be a candidate in such clinical settings.
[Combined irinotecan (CPT-11) and nedaplatin (254-S) therapy for advanced and/or recurrent cervical cancer]. [2018]We performed combination therapy with irinotecan (CPT-11) plus nedaplatin (254-S) for patients with cervical cancer. A total of 9 patients with cervical cancer (5 patients treated in neoadjuvant setting and 4 patients for recurrent disease) were administered 80 mg/m(2) of 254-Sintravenously on day 1 and 50 mg/m(2) of CPT-11 intravenously on day 1, 8 and 15. Treatment was repeated every 4 weeks. The average number of courses administered was 3.8 (range, 2-6). Grade 3 or 4 adverse events were leukopenia in 4 patients, thrombocytopenia in 1 patient and vomiting in 1 patient. The response rate was 40% in the neoadjuvant setting (2 PRs) and 75% in recurrent disease (3 PRs).
Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. [2021]CAR T-cells are autologous T-cells transduced with a chimeric antigen receptor which targets the modified T-cell against a specified cancer antigen. Anti-CD19 CAR T-cells currently represent transformational therapy for relapsed/refractory aggressive B-cell lymphomas where durable remissions can be induced in patients with previously incurable chemotherapy-refractory disease. Three anti-CD19 CAR T-cells are currently Food and Drug Administration and European Medicines Agency approved or in advanced-stage development: axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. Although all targeting CD19 on the surface of malignant (and healthy) B-cells, these products differ from one another in multiple ways including construct, manufacturing, dose, design of pivotal clinical trials, and toxicity profile. Efficacy and safety data for anti-CD19 CAR T-cell therapy in aggressive B-cell lymphomas will be reviewed, as well as novel CAR T-cell designs and strategies for overcoming treatment resistance.
CD19 chimeric antigen receptor-T cells in B-cell leukemia and lymphoma: current status and perspectives. [2022]The approval of tisagenlecleucel and axicabtagene ciloleucel represents a breakthrough in the field of immune and cellular therapy for hematologic malignancies. These anti-CD19 chimeric antigen receptor-T cells (CAR) proved to be highly effective in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and specific histologic subtypes of B-cell non-Hodgkin lymphomas. This expert review aims to summarize the current available research evidence in this field, with a special focus on the different challenges faced by treating physicians, and we also provide future perspectives.
The promise of CAR T-cell therapy in aggressive B-cell lymphoma. [2021]Relapsed or refractory aggressive B-cell lymphoma has an extremely poor prognosis and efforts to develop novel therapies for these patients have failed for almost four decades until the advent of chimeric antigen receptor (CAR) T-cell therapy. Within the last one year, two anti-CD19 CAR T-cell therapy products, axicabtagene ciloleucel and tisagenlecleucel, were approved by the United States Food and Drug Administration for the treatment of relapsed or refractory large B-cell lymphoma after at least two lines of systemic therapy based on multicenter single-arm phase two clinical trials. Here, we will discuss the different components of the CAR construct and their mechanisms of action, the role of conditioning chemotherapy, the efficacy and toxicity observed with anti-CD19 CAR T-cell therapies in aggressive B-cell lymphomas, and emerging strategies to further improve the safety and efficacy of these highly promising approaches.
Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. [2019]Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.