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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06577025




Registration number
NCT06577025
Ethics application status
Date submitted
27/08/2024
Date registered
29/08/2024
Date last updated
26/10/2024

Titles & IDs
Public title
A Study of Different Sequences of Cilta-cel, Talquetamab in Combination With Daratumumab and Teclistamab in Combination With Daratumumab Following Induction With Daratumumab, Bortezomib, Lenalidomide and Dexamethasone in Participants With Standard-risk Newly Diagnosed Multiple Myeloma
Scientific title
A Phase 2, Open-label Study to Evaluate the Efficacy and Safety of Different Sequences of Ciltacabtagene Autoleucel (Cilta-cel), Talquetamab SC in Combination With Daratumumab SC (Tal-D) and Teclistamab SC in Combination With Daratumumab SC (Tec-D) Following Induction With Daratumumab, Bortezomib, Lenalidomide and Dexamethasone (DVRd) in Participants With Standard-risk Newly Diagnosed Multiple Myeloma
Secondary ID [1] 0 0
2023-505792-71-00
Secondary ID [2] 0 0
54767414MMY2093
Universal Trial Number (UTN)
Trial acronym
aMMbition
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cilta-cel
Treatment: Drugs - Talquetamab
Treatment: Drugs - Daratumumab
Treatment: Drugs - Teclistamab
Treatment: Drugs - Bortezomib
Treatment: Drugs - Lenalidomide
Treatment: Drugs - Dexamethasone
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Fludarabine

Experimental: Cohort A: DVRd Induction + Tal-D Consolidation + Cilta-cel - Participants will undergo apheresis followed by 4 cycles of DVRd induction (each cycle is of 28 days) and cilta-cel will be generated from the participants' T-cells selected from the apheresis product. Upon completion of cilta-cel production, product release, and completion of induction, participants will begin consolidation with 4 cycles of Tal-D (each cycle is of 28 days), followed by a conditioning regimen (cyclophosphamide and fludarabine daily for 3 days); cilta-cel will be administered 5 to 7 days after the start of the conditioning regimen.

Experimental: Cohort B: DVRd Induction + Cilta-cel + Tal-D and Tec-D Consolidation - Participants will undergo apheresis followed by 4 cycles of DVRd induction and Cilta-cel will be generated from the participants' T-cells selected from the apheresis product. Upon completion of cilta-cel production, product release and completion of induction, participants will begin consolidation with a conditioning regimen (cyclophosphamide and fludarabine daily for 3 days) with infusion of cilta-cel 5 to 7 days after the start of the conditioning regimen. Following cilta-cel infusion, alternating cycles of Tal-D (Cycle 1, 3, 5, and 7) and Tec-D (Cycle 2, 4, 6, and 8) will be started, no earlier than Day 84 and no later than Day 168 post cilta-cel infusion. Each cycle of Tal-D and Tec-D is 84 days which includes an extended treatment-free interval.


Treatment: Drugs: Cilta-cel
Cilta-cel infusion will be administered intravenously.

Treatment: Drugs: Talquetamab
Talquetamab will be administered subcutaneously.

Treatment: Drugs: Daratumumab
Daratumumab will be administered subcutaneously as a part of DVRd induction and Tal-D and Tec-D consolidation.

Treatment: Drugs: Teclistamab
Teclistamab will be administered subcutaneously.

Treatment: Drugs: Bortezomib
Bortezomib will be administered subcutaneously as a part of induction.

Treatment: Drugs: Lenalidomide
Lenalidomide will be administered orally as a part of induction.

Treatment: Drugs: Dexamethasone
Dexamethasone will be administered orally as a part of induction.

Treatment: Drugs: Cyclophosphamide
Cyclophosphamide will be administered intravenously as a part of conditioning regimen.

Treatment: Drugs: Fludarabine
Fludarabine will be administered intravenously as a part of conditioning regimen.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of Response with Curative Potential
Timepoint [1] 0 0
Up to 5 years
Primary outcome [2] 0 0
Progression Free Survival (PFS) Rate at 3-Year
Timepoint [2] 0 0
At 3-year
Primary outcome [3] 0 0
PFS Rate at 5-Year
Timepoint [3] 0 0
At 5-year
Secondary outcome [1] 0 0
Overall response rate (ORR; Partial response [PR] or better)
Timepoint [1] 0 0
Up to 5 years
Secondary outcome [2] 0 0
CR or Better Rate
Timepoint [2] 0 0
Up to 5 years
Secondary outcome [3] 0 0
Very Good Partial Response (VGPR) or Better Rate
Timepoint [3] 0 0
Up to 5 years
Secondary outcome [4] 0 0
Duration of Response (DOR)
Timepoint [4] 0 0
Up to 5 years
Secondary outcome [5] 0 0
Time to First Response (TTR)
Timepoint [5] 0 0
Up to 5 years
Secondary outcome [6] 0 0
Duration of CR or Better Response
Timepoint [6] 0 0
Up to 5 years
Secondary outcome [7] 0 0
Time to First CR or Better Response
Timepoint [7] 0 0
Up to 5 years
Secondary outcome [8] 0 0
PFS on next line therapy (PFS2)
Timepoint [8] 0 0
Up to 5 years
Secondary outcome [9] 0 0
Overall Survival (OS)
Timepoint [9] 0 0
Up to 5 years
Secondary outcome [10] 0 0
MRD-negative CR Rate
Timepoint [10] 0 0
Up to 5 years
Secondary outcome [11] 0 0
Number of Participants with Treatment-emergent Adverse Events (TEAEs) by Severity
Timepoint [11] 0 0
Up to 5 years
Secondary outcome [12] 0 0
Change from baseline in Health-related quality of life (HRQoL) (symptoms and functioning) using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 item instrument (EORTC-QLQ-C30)
Timepoint [12] 0 0
Up to 5 years

Eligibility
Key inclusion criteria
* Participants with documented new diagnosis of multiple myeloma (MM) according to international myeloma working group (IMWG) diagnostic criteria
* Participants must have standard-risk MM (stage I and II) based on revised International Staging System (R-ISS)
* Participants must be considered fit (score equals to [=] 0) or intermediate-fit (score=1) according to IMWG Frailty Index assessment (based on the Charlson Comorbidity Index, the Katz Activity of Daily Living and the Lawson Instrumental Activities of Daily Living)
* Measurable disease defined as: Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) or urine M-protein level >= 200 milligrams per 24 hours (mg/24 hours); Light chain MM without measurable disease in the serum or the urine: Serum immunoglobulin free light chain >=10 milligrams per deciliter (mg/dL) and abnormal serum immunoglobulin kappa lambda free light chain ratio
* Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any ongoing myelodysplastic syndrome or B-cell malignancy (other than MM). Any history of malignancy, other than MM, which is considered at high risk of recurrence requiring systemic therapy
* Peripheral neuropathy or neuropathic pain of Grade >= 2, as defined by National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
* Known active or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of MM
* Stroke or seizure within 6 months of signing the informed consent form (ICF)
* Plasma cell leukemia at the time of screening (>= 5 percent [%] circulating plasma cells in peripheral blood smears), Waldenstrom macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes(POEMS) syndrome, or primary amyloid light chain amyloidosis with associated organ dysfunction
* Presence of high-risk disease features: (a) Cytogenetic high risk lesions by MM fluorescence in situ hybridization (FISH) including deletion 17p (del[17p])/, t(4;14), t(14;16), amplification 1q (amp[1q21]) (>= 4 copies); (b) Presence of 1 or more extramedullary plasmacytomas
* Seropositive for human immunodeficiency virus (HIV)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/08/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/07/2030
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Iowa
Country [3] 0 0
Brazil
State/province [3] 0 0
Sao Paulo

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Janssen Research & Development, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the rate of response (how effectively treatment is working) with signs of potential cure at 5 years after the start of induction treatment. This is defined as a composite of sustained (at least 2 years) minimal residual disease (MRD) negativity with complete response/stringent complete response (CR/sCR) and a positron emission tomography/computed tomography (PET/CT) scan that does not show any signs of cancer at 5 years. MRD negativity and CR/sCR is defined as no detectable signs of remaining cancer cells after the treatment. This study will also characterize how well the treatments administered work in the study through progression-free survival (PFS). PFS is defined as the length of time during and after the treatment of a disease, that a participant lives with the disease, but it does not get worse.
Trial website
https://clinicaltrials.gov/study/NCT06577025
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical Trial
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Study Contact
Address 0 0
Country 0 0
Phone 0 0
844-434-4210
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT06577025