Clinical study comparing Bortezomib, Lenalidomide, and Dexamethasone (VRd) followed by Ciltacabtagene autoleucel (Cilta-Cel), a CAR-T cell immunotherapy, with Bortezomib, Lenalidomide, and Dexamethasone (VRd) followed by Lenalidomide and Dexamethasone (Rd) in patients with newly diagnosed Multiple Myeloma (MM), for whom no stem cell transplantation is planned as first-line therapy.
Summary description of the study
This is an open-label, worldwide study to assess whether an induction therapy (Induction) with VRd followed by a single dose of Cilta-Cel compared to VRd induction followed by Rd maintenance therapy shows a benefit in efficacy in patients with newly diagnosed MM for whom no bone marrow transplant is planned as first therapy. Approximately 650 patients (325 per study arm) will be randomly assigned in a 1:1 ratio to either standard therapy with VRd induction and subsequent Rd maintenance therapy (Arm A) or treatment with VRd induction and subsequent single dose of Cilta-Cel (Arm B). For patients in Arm B, a separation of certain blood components is performed to obtain the white blood cells. Cilta-Cel is made from the T-cells (blood cell type of the separated blood cells) of the patient. After the manufacture of Cilta-Cel, patients receive a preparatory treatment of Cyclophosphamide and Fludarabine. After infusion of Cilta-Cel, patients enter a treatment-free observation period that lasts until either progression of MM is confirmed in the laboratory or the next myeloma therapy begins. Cilta-Cel is administered 5 to 7 days after the start of the preparatory treatment. In the first 112 days after the Cilta-Cel administration (post-infusion follow-up period), intensive monitoring of patients regarding safety, pharmacokinetics, biomarkers, and efficacy is conducted. When this post-infusion follow-up period is completed (Day 112), patients enter the post-treatment follow-up period. Subsequently, monitoring of patients regarding efficacy continues. For all patients treated with Cilta-Cel, long-term safety monitoring is conducted as part of a separate clinical trial for up to 15 years after the administration of Cilta-Cel.
(BASEC)
Intervention under investigation
Informed consent
Discussion of medical history
Discussion of medication
Physical examination
Neurological examination
Cardiovascular parameters
Discussion of side effects
Handwriting sample
ECG (Electrocardiogram)
Echocardiogram
Magnetic resonance imaging
Computed tomography (CT scan)
X-ray (Chest)
Urine samples
Blood draw/Blood tests
Bone marrow aspiration (Aspiration or core biopsy)
Tumor tissue biopsy/Extramedullary plasmacytoma (MM outside the bone marrow)
Cerebrospinal fluid analysis
Diary
Questionnaires
(BASEC)
Disease under investigation
Multiple Myeloma
(BASEC)
- Patient must be at least 18 years old. - Multiple Myeloma newly diagnosed. - Patient must not be suitable for high-dose chemotherapy followed by stem cell transplantation. (BASEC)
Exclusion criteria
- Patient must not have another cancer. - The Multiple Myeloma must not affect the patient's brain. - No prior therapy for Multiple Myeloma. (BASEC)
Trial sites
Basel, Bern, St. Gallen
(BASEC)
Sponsor
Sponsor: Janssen-Cilag International N.V. Turnhoutseweg 30 2340 Beerse Belgium Sponsor’s representative in Switzerland: Janssen-Cilag AG Gubelstrasse 34 6300 Zug
(BASEC)
Contact
Contact Person Switzerland
Nina Schnüriger
+41 58 2313434
nschnuri@clutterits.jnj.comJanssen-Cilag AG Gubelstrasse 34 6300 Zug
(BASEC)
General Information
Janssen Research & Development, LLC
(ICTRP)
Scientific Information
Janssen Research & Development, LLC
(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Bern
(BASEC)
Date of authorisation
25.05.2022
(BASEC)
ICTRP Trial ID
NCT04923893 (ICTRP)
Official title (approved by ethics committee)
A Phase 3 Randomized Study Comparing Bortezomib, Lenalidomide and Dexamethasone (VRd) followed by Ciltacabtagene Autoleucel, a Chimeric Antigen Receptor T cell (CAR-T) Therapy Directed Against BCMA versus Bortezomib, Lenalidomide, and Dexamethasone (VRd) followed by Lenalidomide and Dexamethasone (Rd) Therapy in Participants with Newly Diagnosed Multiple Myeloma for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy (BASEC)
Academic title
A Phase 3 Randomized Study Comparing Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by Ciltacabtagene Autoleucel, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against BCMA Versus Bortezomib, Lenalidomide, and Dexamethasone (VRd) Followed by Lenalidomide and Dexamethasone (Rd) Therapy in Participants With Newly Diagnosed Multiple Myeloma for Whom Hematopoietic Stem Cell Transplant is Not Planned as Initial Therapy (ICTRP)
Public title
A Study of Bortezomib, Lenalidomide and Dexamethasone (VRd) Followed by Cilta-cel, a CAR-T Therapy Directed Against BCMA Versus VRd Followed by Lenalidomide and Dexamethasone (Rd) Therapy in Participants With Newly Diagnosed Multiple Myeloma for Whom ASCT is Not Planned as Initial Therapy (ICTRP)
Disease under investigation
Multiple Myeloma (ICTRP)
Intervention under investigation
Drug: BortezomibDrug: DexamethasoneDrug: LenalidomideDrug: Cilta-celDrug: CyclophosphamideDrug: Fludarabine (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Inclusion/Exclusion criteria
Inclusion Criteria:
- Documented diagnosis of multiple myeloma (MM) according to International Myeloma
Working Group (IMWG) diagnostic criteria
- Measurable disease at screening as defined by any of the following: Serum monoclonal
paraprotein (M-protein) level greater than or equal to (>=)1.0 gram per deciliter
(g/dL) or urine M-protein level >=200 milligram (mg)/24 hours or Light chain MM in
whom only measurable disease is by serum free light chain (FLC) levels: Serum
immunoglobin (Ig) free light chain >=10 milligrams per deciliter (mg/dL) and
abnormal serum Ig kappa/lambda FLC ratio
- Eastern Cooperative Oncology Group Performance Status grade of 0 or 1
- Not considered for high-dose chemotherapy with Autologous Stem Cell Transplant
(ASCT) due to: Ineligible due to advanced age or Ineligible due to presence of
comorbid condition(s) likely to have a negative impact on tolerability of high-dose
chemotherapy with ASCT or Deferral of high-dose chemotherapy with ASCT as initial
treatment
- A woman of childbearing potential (WOCBP) must have 2 negative highly sensitive
serum or urine pregnancy tests (beta-human chorionic gonadotropin) prior to starting
Bortezomib, Lenalidomide and Dexamethasone (VRd) and must agree to further testing
during the study.
- Clinical laboratory values meeting the following criteria during the screening
phase: hemoglobin greater than or equal to (>=) 8.0 g/dL (>=5 millimoles per liter
[mmol/L]), recombinant human erythropoietin use is permitted platelets >=75
*10^9/L absolute lymphocyte count >=0.3 *10^9/L absolute neutrophil count (ANC)
>=1.0 10^9/L (prior growth factor support is permitted but must be without support
in the 7 days prior to the laboratory test) aspartate aminotransferase (AST) and
alanine aminotransferase (ALT) less than or equal to (<=) 3.0 * upper limit of
normal (ULN) estimated glomerular filtration rate >=40 milliliter per minute/1.73
meter square (mL/min/1.73 m^2) based upon modified diet in renal disease formula
(MDRD-4) calculation or a 24-hour urine collection total bilirubin <=2.0 * ULN
except in participants with congenital hyperbilirubinemia, such as Gilbert syndrome
(in which case direct bilirubin <=2.0 * ULN is required)
Exclusion Criteria:
- Frailty index of >=2 according to Myeloma Geriatric Assessment score
- Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the
National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Version 5
- Known active, or prior history of central nervous system (CNS) involvement or
clinical signs of meningeal involvement of MM
- Stroke or seizure within 6 months of signing Informed Consent Form (ICF)
- Seropositive for human immunodeficiency virus (HIV)
- Vaccinated with live, attenuated vaccine within 4 weeks prior to first dose of VRd
- Participant must not require continuous supplemental oxygen
- Hepatitis B infection
- Hepatitis C infection
- Prior treatment with chimeric antigen receptor T (CAR-T) therapy directed at any
target
- Any therapy that is targeted to B-cell maturation antigen (BCMA) (ICTRP)
not available
Primary and secondary end points
Progression Free Survival (PFS) (ICTRP)
Sustained Minimal Residual Disease (MRD) Negative CR;MRD Negative CR at 9 Months;Overall MRD Negative CR;Overall Survival (OS);Complete Response or Better;Time to Subsequent Anti-myeloma Therapy;Progression Free Survival on Next-line Therapy (PFS2);Number of Participants with Adverse Events (AEs), Abnormalities in Laboratory Parameters, 12-Lead Electrocardiogram (ECG), Physical Examination, and Vital Signs;Arm B: Systemic Cytokine Concentrations;Arm B: Levels of Chimeric Antigen Receptor T cell (CAR-T) Cell Activation Markers;Arm B: Levels of Soluble B-cell Maturation Antigen (BCMA);Arm B: Levels of Cilta-cel Expansion (proliferation), and Persistence;Arm B: Number of Participants with Anti-cilta-cel Antibodies;Arm B: Number of Participants with Presence of Replication Competent Lentivirus;Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score;Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Score;Change from Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Score;Change from Baseline in Health-Related Quality of Life as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score;Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Items;Time to Worsening of Symptoms, Functioning and Overall Well-being (ICTRP)
Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC (ICTRP)
Secondary trial IDs
68284528MMY3004, 2021-001242-35, 2023-505850-16-00, CR109015 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/study/NCT04923893 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available