Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age, Type of Participant, and Disease Characteristic 1. =18 years of age 2. Documented diagnosis of MM according to IMWG diagnostic criteria 3. Measurable disease at Screening as defined by any of the following: • Serum monoclonal paraprotein (M-protein) level =1.0 g/dL or urine M-protein level =200 mg/24 hours; or • Light chain MM in whom only measurable disease is by serum free light chain (FLC) levels: Serum Ig free light chain =10 mg/dL and abnormal serum Ig kappa/lambda FLC ratio. 4. 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. 5. Eastern Cooperative Oncology Group Performance Status grade of 0 or 1 Contraceptive/Barrier Requirements 6. A woman of childbearing potential (WOCBP) must have 2 negative highly sensitive serum or urine pregnancy test (ß-human chorionic gonadotropin) tests prior to starting VRd and must agree to further testing during the study. 7. When a woman is of childbearing potential, the participant must commit either to abstaining continuously from heterosexual intercourse or agree to practice 2 methods of reliable birth control simultaneously, ie, one highly effective method of contraception (failure rate of <1% per year when used consistently and correctly; see examples below) and one other effective method (ie, male latex or synthetic condom, diaphragm, or cervical cap). The participant must agree to remain on both methods of birth control, without interruption, from the time of signing the informed consent or for at least 4 weeks before therapy (whichever is earlier) until at least 4 weeks following the last dose of lenalidomide, 3 months after receiving the last dose of bortezomib, or 1 year after receiving the conditioning regimen (cyclophosphamide and fludarabine) or 1 year after receiving cilta-cel infusion (whichever is later) (Section 10.9). Reliable contraception is indicated even where there has been a history of infertility, unless it is due to hysterectomy. Women of childbearing potential should be referred to a qualified provider of contraceptive methods, if needed. Examples of highly effectivecontraceptives include: • User-independent methods: 1) implantable progestogen-only hormone contraception associated with inhibition of ovulation; 2) intrauterine device; intrauterine hormone releasing system; 3) vasectomized partner. • User-dependent method: progestogen-only hormone contraception associated with inhibition of ovulation (oral or injectable). Estrogen-containing hormonal contraception is contraindicated due to increased risk of thromboembolic events with lenalidomide. • Women of childbearing potential must follow the contraception criteria outlined in the global REVLIMID® (or generic lenalidomide) pregnancy prevention program or equivalent local Risk Evaluation and Mitigation Strategy, whichever is more stringent, as applicable in their region. 8. A man must commit either to abstaining continuously from heterosexual intercourse or a man • Who is sexually active with a WOCBP or a pregnant woman must agree to use a barrier method of contraception (eg, latex or synthetic condom with spermicidal foam/gel/film/cream/suppository), without interruption, from the time of signing the informed consent form (ICF
Exclusion criteria
Exclusion criteria: Medical Condition 1. Frailty index of = 2 according to Myeloma Geriatric Assessment score 2. Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are: • non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured. • skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured. • non-invasive cervical cancer treated within the last 24 months that is considered completely cured. • localized prostate cancer (N0M0): - with a Gleason score of =6, treated within the last 24 months or untreated and under surveillance, - with a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence, or - history of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence. • breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence. • malignancy that is considered cured with minimal risk of recurrence. 3. 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. 4. The following cardiac conditions: • New York Heart Association Stage III or IV congestive heart failure • Myocardial infarction or coronary artery bypass graft =6 months prior to enrollment • History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration • History of severe non-ischemic cardiomyopathy • Screening 12-lead ECG showing a baseline corrected Prolonged corrected QT interval (QTc) >470 msec (for women) and >450 msec (for men), as assessed by 12-lead ECG, except in participants with a pacemaker. • Impaired cardiac function (left ventricular ejection fraction 2.0 x 10^9/L plasma cells by standard differential), Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary amyloid light-chain amyloidosis. 8. Seropositive for human immunodeficiency virus (HIV). 9. Vaccinated with live, attenuated vaccine within 4 weeks prior to first dose of VRd. 10. Hepatitis B infection. In the event the infection status is unclear, quantitative levels are necessary to determine the infection status 11. Hepatitis C infection defined as (anti-hepatitis C virus [HCV] antibody positive or detectable HCV-RNA) or known to have a history of hepatitis C. 12. Participant must not require continuous supplemental oxygen. 13. Contraindications, known life-threatening allergies, hypersensitivity, or intolerance to any of the study treatments including cyclophosphamide or fludarabine (if known) or any of their excipients, including boron, mannitol and dimethyl sulfoxide. 14. Serious underlying medical condition, such as: •
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of bortezomib, lenalidomide, and dexamethasone (VRd) induction followed by a single administration of cilta-cel versus VRd induction followed by lenalidomide and dexamethasone (Rd) maintenance in terms of progression-free survival (PFS);Secondary Objective: 1. To characterize minimal residual disease (MRD) negativity 2. To further compare the efficacy of VRd induction followed by a single administration of cilta-cel versus VRd induction followed by Rd maintenance 3. To characterize the safety of VRd induction followed by a single administration of cilta-cel versus VRd induction followed by Rd maintenance 4. To characterize the pharmacokinetics and pharmacodynamics of cilta-cel 5. To assess the immunogenicity of cilta-cel 6. To determine whether replication competent lentivirus is present in participants that receive cilta-cel 7. To evaluate the patient-reported outcomes (PRO) associated with VRd induction followed by single administration of cilta-cel versus VRd induction followed by Rd maintenance;Primary end point(s): Progression-free survival (PFS) with progression defined by IMWG criteria, or death, whichever occurred first.;Timepoint(s) of evaluation of this end point: From the date of randomization to the date of first documented progressive disease (PD), as defined in the IMWG criteria, or death due to any cause, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Sustained minimal residual disease (MRD) negative complete response (CR), as determined by next generation sequencing (NGS) with sensitivity of 10^-5 and defined by MRD negative CR plus at least 12 months durability of the MRD negative CR status. 2. MRD negative CR at 9 months is defined as the participants who achieve MRD negative status at 9±3 months after the randomization date 3. Overall MRD negative CR 4. Overall survival (OS) 5. CR or better 6. Time to subsequent anti-myeloma therapy 7. PFS on next-line therapy (PFS2) 8. Incidence and severity of AEs, laboratory results and other safety parameters 9. Pharmacokinetic and pharmacodynamic markers by protein, DNA, or RNA analyses, including, but not limited to the depletion of soluble BCMA, systemic inflammatory cytokine concentrations and markers of CAR-T cell expansion (proliferation), and persistence via monitoring CAR-T positive cells and CAR transgene level. 10. Presence of anti-cilta-cel antibodies 11. Presence of replication competent lentivirus. 12. Mean change from baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q), EuroQol Five Dimension Questionnaire (EQ-5D-5L) subscale scores, and the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) items 13. Time to worsening of symptoms, functioning, and overall well-being 14. Proportion of participants with a meaningful improvement in the EORTC QLQ-C30 and MySIm-Q subscale scores using the Patient Global Impression of Severity (PGIS) to calculate the meaningful change threshold ;Timepoint(s) of evaluation of this end point: Followed until the end of the study | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Japan, Korea, Republic of, Netherlands, Norway, Poland, Portugal, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed