CILTACABTAGENE AUTOLEUCEL for Multiple myeloma

Inclusion criteria

• {"criterion_text":"- 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)\n- 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)\n- 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\n- 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\n- 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 local REMS, whichever is more stringent, as applicable in their region.\n- Cohort E: -Measurable disease at Screening - Documented diagnosis of MM according to IMWG criteria -Labs as specified in the protocol\n- Cohort F: - Documented new diagnosis of multiple myeloma according to IMWG diagnostic criteria. - Multiple myeloma classified as standard risk per International Staging System (ISS) stage I or II disease criteria - Received initial therapy as specified in protocol. Acceptable combinations include: a. daratumumab, bortezomib, lenalidomide and dexamethasone (D-VRd) or b. daratumumab, lenalidomide and dexamethasone (D-Rd) or c. a carfilzomib-based triplet or quadruplet regimen - Patient must have a documented efficacy response of VGPR or better, without Progressive Disease prior to enrollment, as assessed per IMWG 2016 criteria. - ECOG Performance Status grade of 0 or 1. For a full list of inclusion criteria, please refer to the protocol"}

Exclusion criteria

• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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 JNJ68284528 or its excipients, including DMSO (refer to Investigator's Brochure)."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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"}

Primary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Defined by the International Myeloma Working Group (IMWG) criteria using next generation sequencing (NGS) or next generation flow (NGF) at a 10^-5 threshold"}

France

Earliest CTIS Part Ii Submission Date

05-03-2024

Latest Decision Or Authorization Date

05-05-2025

Processing Time Days

426

Number Of Sites

3

Number Of Participants

6

Netherlands

Earliest CTIS Part Ii Submission Date

21-02-2024

Latest Decision Or Authorization Date

01-09-2025

Processing Time Days

558

Number Of Sites

2

Number Of Participants

10

Belgium

Earliest CTIS Part Ii Submission Date

21-02-2024

Latest Decision Or Authorization Date

28-08-2025

Processing Time Days

554

Number Of Sites

2

Number Of Participants

15

Spain

Earliest CTIS Part Ii Submission Date

21-02-2024

Latest Decision Or Authorization Date

02-09-2025

Processing Time Days

559

Number Of Sites

2

Number Of Participants

22

Germany

Earliest CTIS Part Ii Submission Date

21-02-2024

Latest Decision Or Authorization Date

29-08-2025

Processing Time Days

555

Number Of Sites

2

Number Of Participants

3

Primary sponsor

Full Name

Janssen - Cilag International

Organisation Type

Pharmaceutical company

Country Of Registered Address

Belgium

Contract research organisations

Name

Parexel International Corp.

Responsibilities

6

Third parties

• {"country":"Germany","full_name":"Cellex Collection Center GmbH","duties_or_roles":"Central cryopreservation","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Ancillare LP","duties_or_roles":"Provision of ancillary supplies","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"6","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Smithers PDS LLC","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Charles River Laboratories International Inc.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"EPL Pathology Archives LLC","duties_or_roles":"Long term lab samples storage","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Integris Bioservices LLC","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Signant Health LLC","duties_or_roles":"3","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}