NCT06574126

Ciltacabtagene Autoleucel in High-Risk Smoldering Multiple Myeloma

Phase II Open-Label, Single Arm, Multicenter Study of Ciltacabtagene Autoleucel in High-Risk Smoldering Multiple Myeloma (GEM-CAR-HiRiSMM)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: PETHEMA Foundation · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open-label, single arm, multicenter, interventional study with Dara-VRD followed by cilta-cel in high-risk smoldering multiple myeloma (SMM) patients. The primary objectives of this trial, related with efficafy and safety of the treatment, are i) to evaluate the proportion of high-risk SMM patients with undetectable minimal residual disease (MRD) at 6 months, 12 months, and thereafter every 12 months up to 5 years after cilta-cel administration as well as the sustained undetectable MRD rate in the intent-to-treat (ITT) population; ii) to annotate frequency and severity of adverse events (AE) and serious adverse events (SAE), as well as data from laboratory tests aslo related with safety such as Immunoglobulin (Ig) G levels, complete blood count (CBC) cytopenia adn T-cell populations. Secondary objectives are related with response to therapy and will measure different categories of response and survival.

Detailed description

This is an open-label, single arm, multicenter, interventional study with Dara-VRD followed by cilta-cel in high-risk smoldering multiple myeloma (SMM) patients. JNJ-68284528 (ciltacabtagene autoleucel \[cilta-cel\]) is an autologous chimeric antigen receptor T cell (CAR-T) therapy that targets B-cell maturation antigen (BCMA), a molecule expressed on the surface of mature B-lymphocytes and malignant plasma cells (PCs). Since the immune system is less impaired in early stages of the disease, high-risk SMM would represent the ideal platform to evaluate the potential of Dara-VRD followed by cilta-cel as a curative approach in high-risk SMM. Study participants will be assigned into 2 groups. Participants in Group 1 will receive a maximum of 2 cycles of Dara-VRD induction therapy followed by apheresis and infusion of cilta-cel. Participants in Group 2 will undergo apheresis followed by Dara-VRD induction and cilta-cel infusion. The primary objective is to assess the efficacy and safety of Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (Dara-VRD) followed by cilta-cel in high-risk SMM. The endpoints for the primary objective will be: * To evaluate the proportion of high-risk SMM patients with undetectable minimal residual disease (MRD) at 6 months, 12 months, and thereafter every 12 months up to 5 years after cilta-cel administration as well as the sustained undetectable MRD rate in the intent-to-treat (ITT) population. MRD will be evaluated in the bone marrow by Next Generation Flow and Next Generation Sequencing with sensitivity level of 10-5. * Nature, frequency, severity, and timing of adverse events (AEs), discontinuations due to AEs, and serious adverse events (SAEs). * Selected safety laboratory test: Immunoglobulin (Ig) G levels, complete blood count (CBC) cytopenia, and cluster of differentiation 4 (CD4+) T lymphocytes (T cells). The key secondary objectives are: * To further evaluate the efficacy of Dara-VRD followed by cilta-cel in high-risk SMM patients as measured by ORR as well as different response categories partial response (PR), very good partial response (VGPR), complete response (CR), and stringent CR (sCR), and duration of response (DOR). * To assess the survival (OS) and progression free survival (PFS) of patients with high-risk SMM.

Conditions

• High Risk Smoldering Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Group 1: Dara-VRD followed by apheresis and cilta-cel infusion	In Group 1, 10 eligible participants will undergo a maximum of two 28-day induction cycles with Dara-VRD. Participants in Group 1 are considered enrolled as the date of signing the Informed Consent Form. This will be followed by apheresis according to institutional standards with the collection target and instructions for processing and shipping apheresis product provided in the Cell Therapy Investigational Product Procedures Manual. Cilta-cel will be generated from T cells selected from the apheresis. Participants for whom apheresis or manufacturing fails will be allowed a second attempt of apheresis. Between apheresis and cilta-cel infusion, participants will be allowed to have stem cell collection using GCSF+/-plerixafor. Cilta-cel will be manufactured by transduction of T cells with an LV vector expressing anti-BCMA CAR, followed by T cell expansion.
DRUG	Group 2: Apheresis followed by Dara-VRD and cilta-cel infusion	In Group 2, 10 eligible participants will undergo apheresis first, according to institutional standards with the collection target and instructions for processing and shipping apheresis product provided in the Cell Therapy Investigational Product Procedures Manual. Study enrollment is defined as the date of signing Informed Consent Form. The apheresis will be followed by a maximum of two 28-day induction cycles with DARA-VRD. Cilta-cel will be generated from T cells selected from the apheresis. Participants for whom the apheresis or manufacturing fails will be allowed a second attempt at apheresis. Between apheresis and cilta-cel infusion, participants will be allowed to have stem cell collection using GCSF+/-plerixafor. Cilta-cel will be manufactured by transduction of T cells with an LV vector expressing anti-BCMA CAR, followed by T cell expansion.

Timeline

• Start date: 2024-09-30
• Primary completion: 2032-09-30
• Completion: 2032-09-30
• First posted: 2024-08-27
• Last updated: 2024-10-26

Locations

1 site across 1 country: Spain

Regulatory

• FDA-regulated drug study