Resumen

The purpose of this study is to determine if the addition of daratumumab to velcade (bortezomib) melphalan-prednisone (VMP) will prolong progression-free survival (PFS) compared with VMP alone in participants with previously untreated multiple myeloma who are ineligible for high dose chemotherapy and autologous stem cell transplant (ASCT).

Descripción detallada

The study consists of 3 phases: Screening Phase (within 21 days prior to randomization), Treatment Phase (Cycle 1 Day 1 to discontinuation of all study treatment), and Follow-up Phase (from discontinuation of all study treatment up to death, lost to follow up, withdrawal of consent, or the study ends, whichever occurs first). Treatment phase will include 2 treatments (Treatment A: participants will receive Velcade MelphalanPrednisone (VMP) alone and Treatment B: participants will receive daratumumab in combination with VMP).Two interim analyses are planned. The first will be to evaluate safety after a total of approximately 100 participants have been treated for at least 2 cycles or discontinued the study treatment. The second will be to evaluate cumulative interim safety and efficacy data, and will be performed when approximately 216 PFS events have been accumulated. The final OS analysis will occur when approximately 382 deaths have occurred. Efficacy will be primarily measured by comparison of PFS between the two treatment arms. Participants' safety will be monitored throughout the study.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Participant must have documented multiple myeloma satisfying the calcium elevation, renal insufficiency, anemia, and bone abnormalities (CRAB) diagnostic criteria, monoclonal plasma cells in the bone marrow greater than or equal to 10 percent (%) or presence of a biopsy proven plasmacytoma, and measurable secretory disease, as assessed by the central laboratory, and defined in protocol
Participants who are newly diagnosed and not considered candidate for high-dose chemotherapy with stem cell transplantation (SCT) due to: being age \>=65 years, or in participants \<65 years: presence of important comorbid conditions likely to have a negative impact on tolerability of high dose chemotherapy with stem cell transplantation
Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
Meet the clinical laboratory criteria as specified in the protocol
A woman of childbearing potential must have a negative serum pregnancy test at screening within 14 days prior to randomization
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, 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 prior to dosing. Reliable contraception is indicated even where there has been a history of infertility, unless due to hysterectomy or bilateral oophorectomy

Criterios de exclusión

Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma
Participant has a diagnosis of Waldenstrom's disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions
Participant has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids before treatment
Participant has 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 4
Participant 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 malignancy 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)
Participant has had radiation therapy within 14 days of randomization
Participant has had plasmapheresis within 28 days of randomization
Participant has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume in 1 second \[FEV1\] \<50% of predicted normal), known moderate or severe persistent asthma within the last 2 years or currently has uncontrolled asthma of any classification (controlled intermittent asthma or controlled mild persistent asthma is allowed)
Participants with known or suspected COPD must have a FEV1 test during screening
Participant is known to be seropositive for human immunodeficiency virus (HIV), known to have hepatitis B surface antigen positivity, or history of to have a history of hepatitis C
Participant has any concurrent medical or psychiatric condition or disease (example active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results, or that in the opinion of the investigator, would constitute a hazard for participating in this study

Intervenciones

drug

Velcade

Participants will receive velcade 1.3 mg/m\^2, as subcutaneous injection, twice weekly at Weeks 1, 2, 4 and 5 in Cycle 1 followed by once weekly at Weeks 1, 2, 4 and 5 in Cycles 2 to 9.

drug

Melphalan

Participants will receive melphalan 9 mg/m\^2, orally, once daily on Days 1 to 4 of each cycle up to Cycle 9.

drug

Prednisone

Participants will receive prednisone 60 mg/m\^2, orally, once daily, on Days 1 to 4 of each cycle up to Cycle 9.

drug

Daratumumab IV

Participants will receive daratumumab 16 mg/kg as intravenous infusion, once weekly, for 6 weeks in Cycle 1 and then once every 3 weeks, in Cycle 2 to 9 and thereafter, once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study .

drug

Dexamethasone

Participants administered with dexamethasone 20 mg IV or PO is given 1 hour or less prior to daratumumab administration as pre medication and prednisone substitute.

drug

Daratumumab SC

Daratumumab SC will be administered by SC injection at a fixed dose of 1800 mg once every 4 weeks until documented progression, unacceptable toxicity, or until the end of study. Following amendment 7, participants can switch from daratumumab IV to daratumumab SC.

A Phase 3, Randomized, Controlled, Open-label Study of VELCADE (Bortezomib) Melphalan-Prednisone (VMP) Compared to Daratumumab in Combination With VMP (D-VMP), in Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High-dose Therapy

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Velcade

Melphalan

Prednisone

Daratumumab IV

Dexamethasone

Daratumumab SC

Ubicaciones

Patrocinadores