A Randomized Study Comparing Bortezomib, Lenalidomide and Dexamethasone (VRd) followed by Ciltacabtagene Autoleucel versus Bortezomib, Lenalidomide, and Dexamethasone (VRd) followed by Lenalidomide and Dexamethasone (Rd) Therapy in Participants with Newly Diagnosed Multiple Myeloma for Whom Stem Cell Transplant is Not Planned as Initial Therapy
- Conditions
- Multiple MyelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-001242-35-IT
- Lead Sponsor
- JANSSEN CILAG INTERNATIONAL NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 650
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
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 (ß-human chorionic gonadotropin) tests prior to starting VRd. The first test must be within 10 to 14 days prior to the start of VRd. The second pregnancy test will be done within 24 hours prior to the start of VRd. The investigator must verify that the results of these tests are negative prior to starting VRd.
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 from the time of signing the informed consent until at least 1 year after receiving cilta-cel infusion or for at least 4 weeks following the last dose of lenalidomide or for 3 months after receiving the last dose of bortezomib (whichever is later). 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 effective contraceptives 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® pregnancy prevention program or equivalent local Risk
Evaluation and Mitigation Strategy, whichever is more stringent, as applicable in their region.
For additional information see section 5.1 of the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 455
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for t
Any potential participant who meets any of the following criteria will be excluded from participating in the study:
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
• Impaired cardiac function (left ventricular ejection fraction <45%) as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan (performed =8 weeks of apheresis)
5. Known active, or prior history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of MM.
6. Stroke or seizure within 6 months of signing ICF.
7. Plasma cell leukemia at the time of screening (>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.
For additional information see section 5.2 of the protocol.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method