Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants with Relapsed or Refractory Multiple Myeloma

Phase 1

Conditions: Multiple myeloma
MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-000255-85-DE

Lead Sponsor: Janssen-Cilag International N.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 498

Inclusion Criteria

1. Subject must be at least 18 years of age.
2.Subject must have had 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 at Screening 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). NOTE: A line of therapy is defined as
1 or more cycles of a planned treatment program.
4. 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.
5.Subject must have achieved a response (partial response [PR] or better based on investigator's determination of response by the IMWG criteria) to at least 1 prior regimen in the past (refer to Attachment 1).
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 be 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
9. A woman of childbearing potential must have a negative urine or serum pregnancy test at screening within 14 days prior to randomization.
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 192
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 288

Exclusion Criteria

1. Subject has received daratumumab or other anti-CD38 therapies previously.
2.Subject is refractory to VELCADE, or another PI, like ixazomib and carfilzomib (ie, subject had progression of disease while receiving VELCADE therapy or within 60 days of ending VELCADE therapy, or another PI therapy, like ixazomib and carfilzomib).
3. Subject is intolerant to VELCADE (ie, discontinued due to any adverse event while on VELCADE treatment.
4.Subject has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic halflives 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 of 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).
5. 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).
6. 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.
7.Subject has a history of malignancy (other than multiple myeloma) within 3 years before the date of randomization (exceptions are squamous and basal cell carcinomas of the skin and 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 3 years).
8. Subject has known meningeal involvement of multiple myeloma.
9.Subject has peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) most recent version.
10.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 <50% of predicted normal.
b. Known moderate or severe persistent asthma, or a history of asthma within the last 2 years (see Attachment 8), or currently has 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).
11.Subject is known to be seropositive for human immunodeficiency virus (HIV) or known to have hepatitis B surface antigen positivity, or known to have a history of hepatitis C.
12. 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.
13.Subject has clinically significant cardiac disease, including:
? Myocardial infarction within 6 months before date of randomization, or unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV).
? Uncontrolled cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE] [most recent version] Grade 2 or higher) o

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

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