Multiple Myeloma
Conditions
Brief summary
The purpose of this study is to evaluate how well (efficacy) cilta-cel works when given with a fludarabine-free lymphodepletion regimen (a process of reducing the number of lymphocytes, a type of white blood cell in the body, typically through chemotherapy), or an alternative administration of cilta-cel infusion following a cyclophosphamide and fludarabine lymphodepletion regimen.
Interventions
DRUGCilta-cel
Cilta-cel will be administered as intravenous infusion.
DRUGCyclophosphamide
Cyclophosphamide will be administered as intravenous infusion.
Induction therapy consist of bortezomib, lenalidomide, and dexamethasone (VRd) or daratumumab, lenalidomide, and dexamethasone (DRd) or daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd), will will be administered.
DRUGFludarabine
Fludarabine will be administered as intravenous infusion.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Documented diagnosis of newly diagnosed multiple myeloma (NDMM) according to the most recent international myeloma working group (IMWG) diagnostic criteria and measurable disease at diagnosis (prior to start of any anti-myeloma therapy): Serum monoclonal paraprotein (M-protein) level greater than equal to (\>=)1.0 grams per deciliter (g/dL) or urine M-protein level \>= 200 milligrams (mg)/24 hours; or light chain multiple myeloma in whom the only measurable disease is by serum free light chain (FLC) levels in the serum: involved serum free light chain \>= 10 mg/dL and abnormal serum free light chain ratio * Not considered a candidate for high-dose chemotherapy with stem cell transplantation due to: (a) Advanced age; or (b) Presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with stem cell transplantation; or (c) Participant refusal of high-dose chemotherapy with stem cell transplantation as initial treatment * Participant must have received at least 3 cycles and no more than 5 cycles of induction therapy. Initially, only participants receiving triplet induction therapy with DRd or VRd will be enrolled. Only after sponsor notification, participants receiving quadruplet DVRd induction therapy may be enrolled (screening can commence as early as during Cycle 3 of induction). Participants must have achieved \>= partial response (PR) on the most recent disease assessment to be enrolled * Eastern cooperative oncology group (ECOG) Performance Status score of 0 or 1 * Must be willing and able to adhere to the lifestyle restrictions specified in the protocol
Exclusion criteria
* Frailty index of \>= 2 according to Myeloma Geriatric Assessment score * Known allergies, hypersensitivity, or intolerance to study intervention or its active agents * Grade 2 or higher ongoing non-hematologic toxicity due to induction therapy, with the exception of grade 2 peripheral neuropathy due to bortezomib * Participants who require continuous supplemental oxygen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Minimal Residual Disease (MRD)-negative Complete Response (CR) After Cilta-cel Infusion | At least 12 months after Cilta-cel infusion on Day 1 | Participants in CR or better who achieve MRD-negative status at 12 months after cilta-cel infusion with a sensitivity of 10\^-5, prior to progressive disease (PD) or subsequent anti-myeloma therapy will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall MRD-negative CR Rate | From study start until progressive disease, subsequent therapy or end of study, whichever is earlier (Up to 3 years and 4 months) | Overall MRD-negative CR is defined as the percentage of participants who achieve MRD-negative CR with a sensitivity of 10\^-5 at any time after enrollment but prior to PD or subsequent anti-myeloma therapy. |
| CR or better status | From study start until progressive disease, subsequent therapy or end of study, whichever is earlier (Up to 3 years and 4 months) | CR or better is defined as the percentage of participants who achieve a CR or stringent complete response (sCR) according to the most recent international myeloma working group (IMWG) criteria. |
| Progression Free Survival (PFS) | From study start until progressive disease, subsequent therapy or end of study, whichever is earlier (Up to 3 years and 4 months) | PFS is defined as the time from the date of enrollment to the date of first documented PD, as defined in the most recent IMWG criteria, or death due to any cause, whichever occurs first. |
| Overall Survival (OS) | Up to 3 years and 4 months | OS is measured from the date of enrollment to the date of the participant's death. |
| Number of Participants with Adverse Event (AE) by Severity | Up to 3 years and 4 months | An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death related to adverse event. |
| Number of Participants with Abnormalities in Laboratory Parameters | Up to 3 years and 4 months | Participants with abnormalities in laboratory parameters (hematology, chemistry) will be reported. |
| Levels of Cilta-cel T-Cell Expansion, and Persistence | Up to 3 years and 4 months | Levels of Cilta-cel T cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported. |
| Number of Participants with Anti-Cilta-Cel Antibodies | Up to 3 years and 4 months | The presence of anti-cilta-cel antibodies will be determined from anti-drug antibody samples collected from each participant. |
| Percentage of Participants with Presence of Replication-competent Lentivirus (RCL) | Up to 3 years and 4 months | Percentage of participants with presence of RCL will be reported. |
Countries
Australia, Spain, United States
Contacts
CONTACTStudy Contact
Outcome results
None listed