Relapsed and lenalidomide-refractory multiple myeloma (MM) MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: JNJ-68284528
Product Code: JNJ-68284528
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: JNJ-68284528
Other descriptive name: J
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be at least 18 years of age. 2. 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 =1.0 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. 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 320 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
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. Was vaccinated with live attenuated vaccines within 4 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of JNJ 68284528 with standard therapy, either PVd or DPd ;Secondary Objective: 1.To further compare the efficacy of JNJ 68284528 with standard therapy, either PVd or DPd 2. To assess the safety profile of JNJ 68284528 3. To characterize the pharmacokinetics and pharmacodynamics of JNJ-68284528 4. To assess the immunogenicity of JNJ 68284528 5. To evaluate the impact of JNJ-68284528 treatment on the health-related quality of life of subjects compared with standard therapy, either PVd or DPd;Primary end point(s): PFS;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) | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Followed until the end of the study (approximately up to 6 years);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. | — |
Countries
Australia, Belgium, Denmark, France, Germany, Israel, Italy, Japan, Netherlands, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed