Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: ciltacabtagene autoleucel
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 descri
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cohort A: -1-3 prior lines of therapy, including PI and IMiD -Lenalidomide refractory -Anti-CD38 mAb exposure not required -PD per IMWG criteria =6 months of last regimen; confirmation may be either central or local -Prior SCT allowed (allo: >6 months before apheresis; auto: >12 weeks before apheresis) Cohort B: -Frontline therapy with PI and IMiD -Transplant and non-transplant patients -Anti-CD38 mAb exposure not required -PD per IMWG criteria =12 months of: a. Autologous SCT b. Start of initial therapy (non-transplanted patients) Cohort C: -Previously treated with PI, IMiD, anti-CD38 mAb and BCMA-directed therapy (as monotherapy or in combination) a. Irrespective of dose level or response to prior BCMA-directed therapy -PD per IMWG criteria a. =12 months of last line of therapy b. =6 months of prior therapy, and refractory or non-responsive to their most recent line of therapy Cohort A, B, C: Measurable disease at Screening as defined by any of the following: -Serum M-protein =1.0 g/dL or urine M-protein level =200 mg/24 hours; or -Light chain MM without measurable disease in serum or urine: Serum immunoglobulin free light chain =10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio -Central screening lab results required for all study patients: Local laboratory assessments may be used to establish measurable disease at Screening, with local laboratory result =125% of requirements -For subjects with neither serum nor urine measurable disease, baseline positron emission tomography/ computed tomography (PET/CT) or whole body magnetic resonance imaging (MRI) may be used to satisfy the measurable disease criteria. -Lab values as defined in the protocol Cohort D: -Newly diagnosed MM per IMWG with 4 to 8 total cycles of initial therapy, including induction, high-dose therapy and ASCT with or without consolidation a. Previously treated for smoldering myeloma not eligible b. Patient treated with consolidation must have received =2 cycles - Received IMiD or PI or both in combination with steroid as part of induction or consolidation regimen -Tx with alkylating therapy (eg, cyclophosphamide) or mAb during induction/ consolidation permitted -Labs as specified in the protocol -women of childbearing potential must follow the contraception criteria outlined in the local global REVLIMID® pregnancy prevention program or equivalent local Risk Evaluation and Mitigation Strategy (REMS), whichever is more stringent, as applicable in their region. -Men should agree to practice contraception according to and for the time frame specified in the local global REVLIMID® pregnancy prevention program or equivalent localREMS, whichever is more stringent, as applicable in their region. Cohort E: -Measurable disease at Screening as defined by any of the following: -Serum M-protein =1.0 g/dL or urine M-protein level =200 mg/24 hours; or -Light chain MM without measurable disease in serum or urine: Serum immunoglobulin free light chain =10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio For participants that have received 1 cycle of anti-myeloma therapy prior to enrollment, measurable disease must be assessed by local laboratory on the most recent evaluation prior to the start of the anti-myeloma therapy. -Central screening lab results required for all study patients: Local laboratory assessments may be used to establish measurable disease at Screening, with local laboratory result =125% of requirements -Not considered candidate
Exclusion criteria
Exclusion criteria: Key Exclusion criteria (All cohorts): -Antitumor treatment washout prior to apheresis -Toxicity from previous anticancer therapy must have resolved to baseline or =Grade 1 except alopecia or peripheral neuropathy - Serious underlying medical condition, eg: a.Clinically significant cardiac conditions (CHF, MI, LVEF <45%) b. Active / Hx of autoimmune disease within 3 yrs c. Dementia or altered mental status d. Serious viral, bacterial or uncontrolled systemic fungal infection e. Seropositive for HIV f. Clinically significant Hepatitis B or C infection - Cumulative dose of corticosteroids equivalent to =70 mg of prednisone =7 days prior to apheresis - Stroke or seizure =6 months - Pregnant, breast-feeding or planning to become pregnant / father child while enrolled in study and until 1 year after receiving a JNJ-68284528 infusion - Contraindications, known life threatening allergies, hypersensitivity, or intolerance to cyclophosphamide, fludarabine, or JNJ-68284528 or its excipients, including DMSO (refer to Investigator’s Brochure). Cohort D: -Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study and until 1 year after receiving a JNJ-68284528 infusion or for 4 weeks following discontinuation of lenalidomide (whichever is later). -Contraindications, known life threatening allergies, hypersensitivity, or intolerance to cyclophosphamide, fludarabine, lenalidomide, or JNJ-68284528 or its excipients, including DMSO (refer to Investigator’s Brochure). Cohort E: Contraindications, known life threatening allergies, hypersensitivity, or intolerance to boron or mannitol, hyaluronidase, sorbitol, corticosteroids, monoclonal antibodies or human proteins, cyclophosphamide, fludarabine, lenalidomide, daratumumab, bortezomib, dexamethasone, or JNJ-68284528 excipients, including DMSO. -Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study and until: 1 year after receiving a JNJ-68284528 infusion, or for 4 weeks following discontinuation of lenalidomide, or until 3 months after daratumumab (whichever is later). -Plans to father a child while enrolled in this study until: 1 year after receiving a JNJ-68284528 infusion, or for 4 weeks following discontinuation of lenalidomide, or until 3 months after daratumumab (whichever is later). Cohort F: - Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. - Prior therapy, prior to apheresis - Received a cumulative dose of corticosteroids equivalent to =70 mg of prednisone within the 7 days prior to apheresis - Ongoing toxicity from previous anticancer therapy must have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy. - Major surgery within 2 weeks prior to apheresis, or surgery planned after apheresis up to 2 weeks after cilta-cel administration. For a full list of exclusion criteria, please refer to the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the overall minimal residual disease (MRD) negative rate of subjects who receive cilta-cel;Secondary Objective: -To evaluate the efficacy of JNJ-68284528 -To further characterize MRD negativity -To characterize the safety of JNJ-68284528 -To characterize the pharmacokinetics and pharmacodynamics of JNJ-68284528 -To assess the immunogenicity of JNJ-68284528;Primary end point(s): MRD negative rate (10-5 threshold) as defined by the International Myeloma Working Group (IMWG) criteria using next generation sequencing (NGS) or next generation flow (NGF);Timepoint(s) of evaluation of this end point: Approximately at 1 year after the last subject for each individual cohort has received his or her initial dose of JNJ-68284528 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Cohorts A, B, C, and F will each be considered complete after the last subject has had two years of follow-up after the initial dose of JNJ-68284528. Cohort D and Cohort E will be considered complete 2 ½ years after the last subject receives their initial dose of JNJ-68284528 ;Secondary end point(s): -Overall Response Rate (ORR) (partial response [PR] or better) as defined by the IMWG response criteria -VGPR, CR, sCR rate as defined by the IMWG response criteria, clinical benefit rate (CBR; CBR = ORR [sCR + CR + VGPR + PR] + minimal response [MR]) -Duration of response (DOR) and time to response (TTR) -MRD negative rate at 12 months for subjects who achieved a complete response (CR MRD neg 12 month) -Time to MRD negativity, duration of MRD negativity, -MRD negative rate across clinical response groups (CR, stringent complete response [sCR], very good partial response [VGPR]) -Incidence and severity of adverse events, laboratory results, and other safety parameters -Pharmacokinetic and pharmacodynamic markers including but not limited to depletion of soluble BCMA and BCMA expressing cells, systemic inflammatory cytokine concentrations and immune related proteins, and markers of CAR-T cell activation, expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level. -Presence of anti- JNJ-68284528 antibodies | — |
Countries
Belgium, France, Germany, Israel, Netherlands, Saudi Arabia, Singapore, Spain, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed