E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed and lenalidomide-refractory multiple myeloma (MM) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028228 |
E.1.2 | Term | Multiple myeloma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy of cilta-cel with standard therapy, either PVd or DPd |
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E.2.2 | Secondary objectives of the trial |
1.To further compare the efficacy of cilta-cel with standard therapy, either PVd or DPd 2. To assess the safety profile of cilta-cel 3. To characterize the pharmacokinetics and pharmacodynamics of cilta-cel 4. To assess the immunogenicity of cilta-cel 5. To evaluate the impact of cilta-cel treatment on the health-related quality of life of subjects compared with standard therapy, either PVd or DPd |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Be at least 18 years of age. 2. Criterion modified per Amendment 2 2.1 Have documented diagnosis of MM as defined by the criteria below: -Multiple myeloma diagnosis according to the IMWG diagnostic criteria -Measurable disease at screening as defined by any of the following: -Serum monoclonal paraprotein (M-protein) level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or -Light chain MM without measurable M-protein in the serum or the urine: Serum free light chain ≥10 mg/dL and abnormal serum free light chain ratio. 3. 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 4. Have documented evidence of PD by IMWG criteria based on investigator’s determination on or within 6 months of their last regimen. 5. 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. 6. Be refractory to lenalidomide per IMWG consensus guidelines (failure to achieve minimal response or progression on or within 60 days of completing lenalidomide therapy). Progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion. For subjects with more than 1 prior line of therapy, there is no requirement to be lenalidomide refractory to the most recent line of prior therapy. However, subjects must be refractory to lenalidomide in at least one prior line. 7. Have an ECOG Performance Status score of 0 or 1 8. Have clinical laboratory values as specified in the protocol.
For additional information see section 5.1 of the protocol |
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E.4 | Principal exclusion criteria |
1.Prior treatment with CAR-T therapy directed at any target. 2. Any previous therapy that is targeted to BCMA. 3. Ongoing toxicity from previous anticancer therapy that has not resolved to baseline levels or to Grade 1 or less; except for alopecia. 4. Subjects with Grade 1 peripheral neuropathy with pain or Grade 2 or higher peripheral neuropathy will not be permitted to receive PVd as standard therapy or bridging therapy; however, subject may receive DPd as standard therapy or bridging therapy. 5. Criterion modified per Amendment 2 5.1. Was vaccinated with live attenuated vaccines within 6 weeks prior to randomization 6. Subject received any antitumor therapy as specified in the protocol, prior to randomization 7. Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. Refer to the protocol for allowed exceptions. 8. 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. 9.1 Contraindications or life-threatening allergies, hypersensitivity, or intolerance to JNJ 68284528 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. 10. Stroke or seizure within 6 months of signing ICF. 11. 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 graft-versus-host disease. Subjects with active graft-versus-host disease are excluded. -An autologous stem cell transplantation ≤ 12 weeks before apheresis. 12. 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Assessed monthly from randomization until disease progression (PD) or death whichever occurs first (approximately up to 6 years) |
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E.5.2 | Secondary end point(s) |
1. Rate of CR/sCR 2. Overall MRD negative rate 3. Rate of MRD negativity in subjects with CR/sCR at 12 months ±3 months 4. Rate of sustained MRD negative status 5. OS 6. ORR 7. PFS on next line of therapy (PFS2) 8. Incidence and severity of adverse events 9. Pharmacokinetic and pharmacodynamic markers including but not limited, to systemic cytokine concentrations, and markers of CAR-T cells, T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level. 10. Presence of anti-JNJ-68284528 antibodies 11. Change from baseline in health-related quality of life (HRQoL) subscale scores from the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q), EuroQol Five Dimension Questionnaire (EQ-5D-5L), Patient Global Impression of Severity (PGIS), and the Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) items. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Followed until the end of the study (approximately up to 6 years) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenecity and biomarker assessments including immunophenotyping and CyTOF/PBMC (TCR Seq)/Plasma |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Israel |
Japan |
United Kingdom |
United States |
Belgium |
Denmark |
France |
Germany |
Italy |
Netherlands |
Spain |
Sweden |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study is when approximately 250 deaths have occurred in the study. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 26 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 2 |