A Study Comparing Daratumumab, Lenalidomide, and Dexamethasone with Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma
- Conditions
- Multiple myelomaMedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2013-005525-23-BE
- Lead Sponsor
- Janssen-Cilag International N.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 560
1. Subject must be at least 18 years of age.
2. Subject must have documented multiple myeloma as defined by the
criteria below:
? Monoclonal plasma cells in the bone marrow =10% at some point in their disease history or presence of a biopsy proven plasmacytoma.
? Measurable disease as defined by any of the following:
- IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level =1.0 g/dL or urine M-protein level =200 mg/24 hours; or
- IgA, IgD, IgE, IgM multiple myeloma: serum M-protein level =0.5 g/dL or urine M-protein level =200 mg/24 hours; or
- Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain =10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.
3. Subject must have received at least 1 prior line of therapy for multiple myeloma (refer to
Attachment 1).
4. Subject must have achieved a response (PR or better based on investigator's determination of response by the IMWG criteria) to at least one prior regimen (refer to Attachment 1).
5. Subject must have documented evidence of progressive disease (PD) based on investigator's determination of response by the IMWG criteria on or after their last regimen.
6. Subject must have an ECOG Performance Status score of 0, 1, or 2 (refer to Attachment 2).
7. For subjects experiencing toxicities resulting from previous therapy (including peripheral neuropathy), the toxicities must have resolved or stabilized to =Grade 1.
8. Women of childbearing potential must commit to either abstain continuously from heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously. This includes one highly effective form of contraception (tubal ligation, intrauterine device [IUD], hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants] or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin 4 weeks prior to dosing. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy.
9. A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at Screening, first within 10 to 14 days prior to dosing and the second within 24 hours prior to dosing. For requirements during the Treatment Phase, please see Section 4.3.
10. Each subject (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Subjects must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, as referenced in the ICF.
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 280
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 280
1. Subject has received daratumumab or other anti-CD38 therapies previously
2. Subject's disease shows evidence of refractoriness or intolerance to lenalidomide. If previously treated with a lenalidomide-containing regimen, the subject is excluded if he or she:
? Discontinued due to any adverse event related to prior lenalidomide treatment (history of thromboembolism due to lenalidomide is allowed if subject is anticoagulated per the American Society of Clinical Oncology [ASCO] 2013 guideline) (Lyman 2013)26,or
?If, at any time point, the subject was refractory to any dose of lenalidomide. Refractory to lenalidomide is defined either:
-Subjects whose disease progresses within 60 days after the last dose of lenalidomide;or
-Subjects whose disease is nonresponsive while on lenalidomide. Nonresponsive disease is defined as either failure to achieve at least an MR or development of PD while on lenalidomide
3.Subject has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives of the treatment, whichever is longer, before the date of randomization.The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day
for a maximum 4 days) before treatment. A list of anti-myeloma treatments with the corresponding pharmacokinetic half-lives is provided in the Site Investigational Product Procedures Manual (SIPPM).
4.Subject has received ASCT within 12 weeks before the date of randomization,or the subject has previously received an allogenic stem
cell transplant (regardless of timing)
5.Subjects planning to undergo a stem cell transplant prior to progression of disease on this study,ie, these subjects should not be enrolled in order to reduce disease burden prior to transplant
6.Subject has a history of malignancy (other than multiple myeloma) within 5 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 5 years)
7. Subject has known meningeal involvement of multiple myeloma
8.Subject has either of the following:
a) Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 is <50% of predicted normal
b) Known moderate or severe persistent asthma, within the past 2 years (see Attachment 9), uncontrolled asthma of any classification. Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate in the study
9.Subject is known to be seropositive for human immunodeficiency virus (HIV), known to have hepatitis B surface antigen positivity, or known to
have a history of hepatitis C.
10. Subject has any concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study.
11.Subject has clinically significant cardiac disease,including:
?Myocardial infarction within 6 months before Cycle1,Day1,or unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstab
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