CAR-T Therapy for Multiple Myeloma
(CARTITUDE-2 Trial)
Recruiting in Palo Alto (17 mi)
+49 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Janssen Research & Development, LLC
Must not be taking: Corticosteroids, BCMA-targeted, CAR-T
Disqualifiers: Active infections, Autoimmune, CNS involvement, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?This trial is testing a treatment called JNJ-68284528. It aims to help patients who still have small amounts of cancer cells after their initial treatment. The treatment works by finding and killing these leftover cancer cells to prevent the disease from coming back.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop taking your current medications. However, it mentions that ongoing toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less, which might imply adjustments to your current treatment. It's best to discuss your specific medications with the trial coordinators.
What data supports the effectiveness of the treatment Carvykti (cilta-cel) for multiple myeloma?
In a study, Carvykti (cilta-cel) showed a 100% overall response rate in patients with relapsed or refractory multiple myeloma, with 87.5% achieving a very good partial response or better. This suggests that the treatment is highly effective for this condition.
12345Is CAR-T therapy (cilta-cel) safe for humans?
Cilta-cel, a CAR-T therapy for multiple myeloma, has shown a generally tolerable safety profile, with most side effects being manageable. Common side effects include cytokine release syndrome (a reaction that can cause fever and low blood pressure) and other adverse events, but serious neurotoxicity was not reported in the studies.
15678How is the treatment JNJ-68284528 (Carvykti) different from other treatments for multiple myeloma?
JNJ-68284528 (Carvykti) is a unique treatment for multiple myeloma because it uses CAR-T cell therapy, where a patient's own T cells are modified to target and kill cancer cells. This approach is different from traditional treatments like chemotherapy or stem cell transplants, as it specifically targets the B cell maturation antigen (BCMA) on myeloma cells, offering a promising option for patients with relapsed or refractory multiple myeloma.
3491011Eligibility Criteria
This trial is for multiple myeloma patients with varying treatment histories. Some must have tried specific therapies and be refractory to lenalidomide, while others may be newly diagnosed or ineligible for certain treatments due to age or comorbidities. Participants need a measurable level of disease and should be in good physical condition (ECOG grade 0-1).Inclusion Criteria
I've had 1-3 treatments for my condition, including specific therapies, and one didn't work as expected.
I have newly diagnosed multiple myeloma and have undergone 4 to 8 cycles of initial treatment.
I am not a candidate for high-dose chemotherapy with stem cell transplant due to age, health issues, or personal choice.
+10 more
Exclusion Criteria
My multiple myeloma has affected or previously affected my brain or spinal cord.
You have a serious medical condition such as active infection needing strong antibiotics, uncontrolled fungal infection, active autoimmune disease, recent history of autoimmune disease, dementia, Parkinson's disease, or other brain disorders.
I have no active cancers except for certain treated or low-risk cases.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Lymphodepletion
Participants undergo lymphodepletion prior to receiving JNJ-68284528 infusion
1 week
Treatment
Participants receive a single infusion of JNJ-68284528, with some cohorts receiving additional treatments such as lenalidomide
1 day for infusion, followed by monitoring
Follow-up
Participants are monitored for safety, effectiveness, and MRD status after treatment
Up to 2 years and 6 months
Open-label extension (optional)
Participants may continue to be monitored or receive additional treatment based on their response and MRD status
Long-term
Participant Groups
The study tests JNJ-68284528, a CAR-T therapy targeting BCMA, alongside other drugs like dexamethasone, lenalidomide, daratumumab, and bortezomib. It aims to assess the rate at which participants achieve minimal residual disease negativity.
1Treatment groups
Experimental Treatment
Group I: JNJ-68284528Experimental Treatment5 Interventions
Single group assignment-Post lymphodepletion, JNJ-68284528 single infusion given to Part A participants: Cohort A(Progressive disease post 1-3 prior lines of therapy), Cohort B(Early relapse post front-line), Cohort C(Relapsed/refractory multiple myeloma post PI, IMiD,anti-CD38,anti-BCMA therapy), Cohort D(Less than CR post ASCT front-line therapy, some participants will receive JNJ-68284528 then lenalidomide), Cohort F(Newly diagnosed multiple myeloma \[NDMM\], standard risk \[International Staging System Stage I/II\] and post initial therapy); Cohort E(NDMM,transplant not planned,high risk disease) will first receive quadruplet induction regimen of daratumumab,bortezomib,lenalidomide and dexamethasone(D-VRd) then lymphodepletion and JNJ-68284528 then consolidation regimen of lenalidomide. Part B:Cohort G(NDMM,transplant not planned) will receive daratumumab, lenalidomide and dexamethasone followed by cilta-cel; Cohort H(NDMM,transplant-eligible) will receive D-VRd followed by cilta-cel.
JNJ-68284528 is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Carvykti for:
- Relapsed or refractory multiple myeloma after one or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide
🇪🇺 Approved in European Union as Carvykti for:
- Relapsed and refractory multiple myeloma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Kansas Cancer CenterWestwood, KS
Norton Cancer InstituteLouisville, KY
University of PennsylvaniaPhiladelphia, PA
Yale University School Of MedicineNew Haven, CT
More Trial Locations
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Who Is Running the Clinical Trial?
Janssen Research & Development, LLCLead Sponsor
References
Cilta-cel OK'd for Multiple Myeloma. [2022]The FDA has approved ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell therapy targeting BCMA, as a fifth-line option for patients with relapsed/refractory multiple myeloma. Cilta-cel is the second agent in its class to get a regulatory thumbs-up in less than a year.
Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy. [2023]Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior BCMA-TT cohort had a lower overall response rate (74% versus 88%; p = 0.021), median duration of response (7.4 versus 9.6 months; p = 0.03), and median progression-free survival (3.2 months versus 9.0 months; p = 0.0002) compared to the cohort without prior BCMA-TT. All five patients who received a prior anti-BCMA CAR T responded to ide-cel, and survival outcomes were best for this subgroup. In conclusion, treatment with ide-cel yielded meaningful clinical responses in real-world patients exposed to a prior BCMA-TT, though response rates and durability were suboptimal compared to those not treated with a prior BCMA-TT.
Specific Targeting of Multiple Myeloma by Dual Split-signaling Chimeric Antigen Receptor T cells Directed against CD38 and CD138. [2023]The success of B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T cells illustrates the potential of this novel therapy for multiple myeloma. Nonetheless, broadening CAR T-cell therapy beyond BCMA requires inventive strategies as there are only a few multiple myeloma- or plasma cell-specific target antigens. We investigated the feasibility of achieving multiple myeloma specificity by dual-split CD38/CD138 CAR targeting, whereby the stimulatory and costimulatory signals for T-cell activation are split into two separate stimulatory (sCAR) and costimulatory CARs (cCAR).
Phase 2 results of idecabtagene vicleucel (ide-cel, bb2121) in Japanese patients with relapsed and refractory multiple myeloma. [2023]In the phase 2 KarMMa trial, patients with relapsed/refractory multiple myeloma (RRMM) achieved deep and durable responses with idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T cell therapy. Here we report a sub-analysis of the Japanese cohort of KarMMa.
Ciltacabtagene autoleucel in patients with relapsed/refractory multiple myeloma: CARTITUDE-1 (phase 2) Japanese cohort. [2022]Chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen have shown positive responses in patients with multiple myeloma (MM). The phase 2 portion of the CARTITUDE-1 study of ciltacabtagene autoleucel (cilta-cel) included a cohort of Japanese patients with relapsed/refractory MM. Following a conditioning regimen of cyclophosphamide (300 mg/m2 ) and fludarabine (30 mg/m2 ), patients received a single cilta-cel infusion at a target dose of 0.75 × 106 (range, 0.5-1.0 × 106 CAR-positive viable T cells/kg). The primary endpoint was overall response rate (ORR; defined as partial response or better) by International Myeloma Working Group criteria. A key secondary endpoint was the rate of very good partial response (VGPR) or better (defined as VGPR, complete response, stringent complete response). This first analysis was performed at 6 months after the last patient received cilta-cel. Thirteen patients underwent apheresis, nine of whom received cilta-cel infusion. Eight patients who received cilta-cel at the target dose responded, yielding an ORR of 100%. Seven of eight (87.5%) patients achieved a VGPR or better. One additional patient who received a below-target dose of cilta-cel also achieved a best response of VGPR. MRD negativity (10-5 threshold) was achieved in all six evaluable patients. Eight of nine (88.9%) patients who received cilta-cel infusion experienced a grade 3 or 4 adverse event, and eight (88.9%) patients experienced cytokine release syndrome (all grade 1 or 2). No CAR-T cell neurotoxicity was reported. A positive benefit/risk profile for cilta-cel was established for heavily pretreated Japanese patients with relapsed or refractory MM.
Ciltacabtagene autoleucel for the treatment of multiple myeloma. [2023]While treatment options for multiple myeloma (MM) are continuing to expand, this disease remains one characterized by requiring multiple lines of therapy, with generally decreasing effectiveness of each subsequent line. The development of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy has proven an exception to this rule. In the trial that led to approval of the BCMA CAR T-cell therapy ciltacabtagene autoleucel (cilta-cel) by the U.S. Food and Drug Administration (FDA), deep and durable response rates were observed in heavily pretreated patients. In this review we summarize the available clinical trial data for cilta-cel, including discussion on notable adverse events, as well as discuss ongoing studies that are likely to lead to paradigm changes in the management of MM. In addition, we discuss the issues that currently surround the real-world utilization of cilta-cel.
Patient Perceptions Regarding Ciltacabtagene Autoleucel Treatment: Qualitative Evidence From Interviews With Patients With Relapsed/Refractory Multiple Myeloma in the CARTITUDE-1 Study. [2023]Ciltacabtagene autoleucel (cilta-cel), a novel chimeric antigen receptor T (CAR-T) cell therapy, has demonstrated early, deep, and durable clinical responses in heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), and improvements in health-related quality of life (HRQoL) in CARTITUDE-1 (NCT03548207). Patient perspectives on treatment provide context to efficacy outcomes and are an important aspect of therapeutic evaluation.
Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma. [2022]Ciltacabtagene autoleucel (also known as cilta-cel) is a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) on the surface of cancer cells in B cell malignancies, such as multiple myeloma (MM). It is a second-generation CAR that is outfitted with an ectodomain comprising two BCMA-binding single chain variable fragment (ScFv) domains, a transmembrane domain, and an endodomain possessing CD3ζ and 4-1BB. Cilta-cel is an autologous, gene-edited CAR T-cell that is prepared by collecting and modifying the recipient's T-cells to create a patient personalized treatment in the laboratory to be infused back. This CAR T-cell product exceptionally entails CARs with two BCMA-targeting single-domain antibodies that detect two epitopes of BCMA expressed on the malignant cells of MM. Cilta-cel is the current addition to the treatment armamentarium of relapsed or refractory (r/r) MM after its approval by the FDA on February 28, 2022, based on the results of the Phase 1b/2 CARTITUDE-1 study. It was the second approved anti-BCMA CAR T-cell product after idecabtagene vicleucel (ide-cel) to treat myeloma patients. It induces early, deep, and long-lasting responses with a tolerable safety profile in r/r MM. Cilta-cel-treated myeloma patients may potentially experience adverse effects ranging from mild to life-threatening, but they are mostly manageable toxicities. Besides, it has a consistent safety profile upon a longer follow-up of patients. Cilta-cel generally outperforms ide cel in terms of efficacy in MM, but shows comparable adverse events. This review highlights the current updates on cilta-cel efficacy, adverse events, comparison with ide-cel, and its future direction in the treatment of MM.
Chimeric antigen receptor T cell therapy for multiple myeloma. [2020]Chimeric antigen receptor (CAR) T cell therapy is a new cancer immunotherapy targeting cancer-specific cell surface antigen. CD19-CAR T cells have been already shown to be very effective to B cell leukemia/lymphoma. Now, many researchers are developing CAR T cells for multiple myeloma. CAR T cells targeting B cell maturation antigen (BCMA) showed promising efficacy in early phase clinical trials. We have recently reported that CAR T cells targeting the activated integrin β7 can selectively eradicate MM cells including CD19+ clonotypic B cells and are preparing a clinical trial.
Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma. [2020]Multiple myeloma (MM), considered an incurable hematological malignancy, is characterized by its clonal evolution of malignant plasma cells. Although the application of autologous stem cell transplantation (ASCT) and the introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have doubled the median overall survival to eight years, relapsed and refractory diseases are still frequent events in the course of MM. To achieve a durable and deep remission, immunotherapy modalities have been developed for relapsed/refractory multiple myeloma (RRMM). Among these approaches, chimeric antigen receptor (CAR) T-cell therapy is the most promising star, based on the results of previous success in B-cell neoplasms. In this immunotherapy, autologous T cells are engineered to express an artificial receptor which targets a tumor-associated antigen and initiates the T-cell killing procedure. Tisagenlecleucel and Axicabtagene, targeting the CD19 antigen, are the two pacesetters of CAR T-cell products. They were approved by the US Food and Drug Administration (FDA) in 2017 for the treatment of acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). Their development enabled unparalleled efficacy in combating hematopoietic neoplasms. In this review article, we summarize six promising candidate antigens in MM that can be targeted by CARs and discuss some noteworthy studies of the safety profile of current CAR T-cell therapy.
Chimeric antigen receptor T cell therapies for multiple myeloma. [2020]Multiple myeloma (MM) is the second most common hematologic malignancy and remains incurable despite the advent of numerous new drugs such as proteasome inhibitors (PIs), immunomodulatory agents (IMiDs), and monoclonal antibodies. There is an unmet need to develop novel therapies for refractory/relapsed MM. In the past few years, chimeric antigen receptor (CAR)-modified T cell therapy for MM has shown promising efficacy in preclinical and clinical studies. Furthermore, the toxicities of CAR-T cell therapy are manageable. This article summarizes recent developments of CAR-T therapy in MM, focusing on promising targets, new technologies, and new research areas. Additionally, a comprehensive overview of antigen selection is presented along with preliminary results and future directions of CAR-T therapy development.