Phase 3 Randomized Trial of Ciltacabtagene Autoleucel vs. Pomalidomide, Bortezomib, and Dexamethasone or Daratumumab, Pomalidomide, and Dexamethasone in Relapsed Lenalidomide-Refractory Multiple Myeloma
- Trial ID
- 2023-506588-32-00
- Protocol
- 68284528MMY3002
- Sponsor
- Janssen Cilag International
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 3 randomized study is to compare the **efficacy** of cilta-cel, a chimeric antigen receptor T cell (CAR-T) therapy directed against BCMA, with standard therapy regimens, either Pomalidomide, Bortezomib, and Dexamethasone (PVd) or Daratumumab, Pomalidomide, and Dexamethasone (DPd), in subjects with relapsed and lenalidomide-refractory **multiple myeloma**. This comparison is clinically relevant as it aims to determine the potential superiority of cilta-cel in improving patient outcomes in a population with limited treatment options due to resistance to lenalidomide.
Participants
The clinical trial involves a total of **164 participants** diagnosed with **Relapsed and Lenalidomide-Refractory Multiple Myeloma**. The study population includes both male and female subjects, aged 18 years and older, who have a documented diagnosis of multiple myeloma according to the International Myeloma Working Group (IMWG) diagnostic criteria. Participants have received 1 to 3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), and must be refractory to lenalidomide. The trial population was selected based on specific inclusion criteria, such as having an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1, and meeting clinical laboratory values as specified in the protocol. The study also considers vulnerable populations. Lifestyle factors such as diet and physical activity are not specified in the available data. The selection process ensures that participants have measurable disease at screening and have shown disease progression by IMWG criteria within a defined timeframe relative to their last treatment regimen.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy of **cilta-cel** compared to standard therapies in patients with **relapsed and lenalidomide-refractory multiple myeloma**. The trial will involve two arms: one receiving the investigational product, **cilta-cel**, and the other receiving standard therapy, either **pomalidomide**, **bortezomib**, and **dexamethasone** (PVd) or **daratumumab**, **pomalidomide**, and **dexamethasone** (DPd). The primary endpoint is progression-free survival (PFS). The estimated duration of the trial is from June 2020 to June 2027, with participant involvement expected to last up to 78 weeks, depending on the treatment arm and individual response.
Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, documented diagnosis of multiple myeloma, and previous treatment history. Following randomization, participants will attend regular follow-up visits to monitor treatment response and safety. These visits will include assessments of disease progression, laboratory tests, and adverse event monitoring. The end-of-study visit will occur after the completion of the treatment period or upon early termination, which may be due to disease progression, unacceptable toxicity, or withdrawal of consent.
Inclusion criteria require participants to be at least 18 years old, have a documented diagnosis of multiple myeloma, and have received 1 to 3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD). Participants must also be refractory to lenalidomide and have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Conditions for early termination from the study include disease progression, adverse events, or participant withdrawal. The trial aims to provide valuable data on the efficacy and safety of cilta-cel in comparison to standard therapies for this patient population.
Treatment
The clinical trial involves several treatments, including **Pomalidomide**, which is administered in the form of hard capsules. The pharmaceutical form is a capsule, hard, and it is taken orally. The treatment period for Pomalidomide is up to 78 weeks. The product is manufactured by Janssen-Cilag International N.V. and Bristol-Myers Squibb Pharma EEIG, with various dosages available, including 1 mg, 2 mg, 3 mg, and 4 mg hard capsules. The active substance is of chemical origin.
**Dexamethasone** is another treatment used in the trial, available in tablet form. It is administered orally, with a maximum treatment period of 78 weeks for some formulations and up to 4865 days for others. The product is provided by MIBE GmbH Arzneimittel, Aspen Pharma Trading Limited, and Merck Healthcare Germany GmbH. The active substance is chemically derived.
**Bortezomib** is included in the trial as a comparator treatment. It is administered subcutaneously, with a maximum treatment period of 78 weeks. The active substance is of chemical origin.
**Daratumumab** is administered as a solution for injection, subcutaneously, with a maximum treatment period of 78 weeks. The product is manufactured by Janssen-Cilag International NV, and the active substance is a protein of other origin.
**Fludarabine** is used as an auxiliary treatment, administered intravenously. The pharmaceutical form is PHF675, with a maximum treatment period of 3 weeks. The active substance is of chemical origin.
**Cyclophosphamide** is another auxiliary treatment, administered intravenously. The pharmaceutical form is PHF00231MIG, with a maximum treatment period of 3 weeks. The active substance is of chemical origin.
**Ciltacabtagene autoleucel** is the experimental medication in this trial, administered as a dispersion for infusion intravenously. The treatment period is limited to a single administration. The product is manufactured by Janssen-Cilag International NV, and the active substance is a structurally diverse substance used in cell therapy. The clinical trial will utilize clinical material, with potential differences in the lentiviral vector manufacturing process compared to the authorized product.
Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the treatment protocols. The trial aims to compare the efficacy of ciltacabtagene autoleucel with standard therapies, including Pomalidomide, Bortezomib, and Dexamethasone (PVd) or Daratumumab, Pomalidomide, and Dexamethasone (DPd) in subjects with relapsed and lenalidomide-refractory multiple myeloma.
Efficacy
The efficacy of the clinical trial will be assessed primarily through the endpoint of **progression-free survival (PFS)**. This parameter will be used to evaluate the effectiveness of the investigational therapy, JNJ-68284528, a Chimeric Antigen Receptor T cell (CAR-T) therapy directed against BCMA, in comparison to standard therapies, which include Pomalidomide, Bortezomib, and Dexamethasone (PVd) or Daratumumab, Pomalidomide, and Dexamethasone (DPd) in subjects with relapsed and lenalidomide-refractory multiple myeloma.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Be at least 18 years of age.
- Have documented diagnosis of MM as defined by the criteria below:-Multiple myeloma diagnosis according to the IMWG diagnostic criteria -Measurable disease at screening
- Have received 1 to 3 prior lines of therapy including a PI and IMiD. Subject must have undergone at least 1 complete cycle of treatment for each line of therapy, unless PD was the best response to the line of therapy
- Have documented evidence of PD by IMWG criteria based on investigator's determination on or within 6 months of their last regimen.
- Subjects with only 1 prior line of therapy must have progressed within 36 months of a stem cell transplant or if not transplanted, then within 42 months of starting initial therapy.
- Be refractory to lenalidomide per IMWG consensus guidelines in at least one prior line of therapy.
- Have an ECOG Performance Status score of 0 or 1
- Have clinical laboratory values as specified in the protocol. For additional information see section 5.1 of the protocol
Exclusion Criteria
- Prior treatment with CAR-T therapy directed at any target.
- Any previous therapy that is targeted to BCMA.
- Ongoing toxicity from previous anticancer therapy that has not resolved to baseline levels or to Grade 1 or less; except for alopecia.
- Subjects with ongoing peripheral neuropathy may be limited to DPd as standard therapy or bridging therapy
- Was vaccinated with live attenuated vaccines within 6 weeks prior to randomization
- Subject received any antitumor therapy as specified in the protocol, prior to randomization
- Active malignancies other than the disease being treated under study. Refer to the protocol for allowed exceptions.
- Plasma cell leukemia at the time of screening, Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary AL amyloidosis.
- Contraindications or life-threatening allergies, hypersensitivity, or intolerance to cilta-cel or its excipients, including dimethylsulfoxide, or to fludarabine, cyclophosphamide, tocilizumab, pomalidomide, dexamethasone.- Subjects with contraindications or life-threatening allergies, hypersensitivity, or intolerance to daratumumab will not be permitted to receive DPd as standard therapy or bridging therapy; however, subjects may receive PVd as standard therapy or bridging therapy. Likewise, subjects with contraindications or life-threatening allergies, hypersensitivity, or intolerance to bortezomib will not be permitted to receive PVd as standard therapy or bridging therapy; but may receive DPd as standard therapy or bridging therapy.
- Stroke or seizure within 6 months of signing ICF.
- Received either of the following:-An allogenic stem cell transplant within 6 months before apheresis. Subjects who received an allogeneic transplant must have stopped all immunosuppressive medications for 6 weeks without signs of graftversus-host disease. Subjects with active graft-versus-host disease are excluded.-An autologous stem cell transplantation ≤ 12 weeks before apheresis.
- Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of MM. For additional information, see section 5.2 of the protocol
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 30 Jun 2020 | 15 |
 Denmark | Not Recruiting | 30 Jun 2020 | 4 |
 France | Not Recruiting | 30 Jun 2020 | 34 |
 Germany | Not Recruiting | 30 Jun 2020 | 11 |
 Greece | Not Recruiting | 30 Jun 2020 | 1 |
 Italy | Not Recruiting | 30 Jun 2020 | 33 |
 The Netherlands | Not Recruiting | 30 Jun 2020 | — |
 Poland | Not Recruiting | 30 Jun 2020 | 24 |
 Spain | Not Recruiting | 30 Jun 2020 | 82 |
 Sweden | Not Recruiting | 30 Jun 2020 | 6 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Pomalidomide | Comparator | CAPSULE, HARD | ORAL USE | 0 | 78 | PRD11001952 |
Imnovid 3 mg hard capsules | Comparator | HARD CAPSULES | ORAL USE | 0 | 78 | PRD9260806 |
Imnovid 1 mg hard capsules | Comparator | HARD CAPSULES | ORAL USE | 0 | 78 | PRD9260804 |
Imnovid 2 mg hard capsules | Comparator | HARD CAPSULES | ORAL USE | 0 | 78 | PRD9260805 |
Imnovid 4 mg hard capsules | Comparator | HARD CAPSULES | ORAL USE | 0 | 78 | PRD9260808 |
Pomalidomide | Comparator | CAPSULE, HARD | ORAL USE | 0 | 78 | PRD11001955 |
Pomalidomide | Comparator | CAPSULE, HARD | ORAL USE | 0 | 78 | PRD11001953 |
DARZALEX 1800 mg solution for injection | Comparator | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 0 | 78 | PRD8157846 |
Imnovid 3 mg hard capsules | Comparator | HARD CAPSULES | ORAL USE | 0 | 78 | PRD9260813 |
BORTEZOMIB | Comparator | PHF00231MIG | SUBCUTANEOUS USE | 0 | 78 | SCP13241261 |