A Study of Combination of Daratumumanb and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants with Previously Untreated Multiple Myeloma

• Register: EUCTR
• Last refreshed on: 5 July 2021
• Main ID: EUCTR2014-002272-88-BE
• Date of registration: 16/09/2014
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• Public title: A Study of Combination of Daratumumanb and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants with Previously Untreated Multiple Myeloma
• Scientific title: 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
• Date of first enrolment: 02/12/2014
• Target sample size: 700
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002272-88
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Croatia, Czech Republic, Czechia, Georgia, Germany, Greece, Hungary, Italy, Japan, North Macedonia, Poland, Portugal, Romania, Russian Federation, Serbia, Spain, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International N.V.

• Name: Clinical Registry group
• Affiliation: Janssen-Cilag International N.V.

Key inclusion & exclusion criteria

Inclusion criteria:
- 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
- A woman of childbearing potential must have a negative serum pregnancy test at screening within 14 days prior to randomization

For a full overview of the inclusion criteria, please see the protocol amendment.
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 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 640

Exclusion criteria:
- Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiplemyeloma
- 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
stem cell transplantation (SCT) for multiple myeloma, with the exception of an emergency use of a short course 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 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

For a full overview of the exclusion criteria, please see the protocol amendment.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple myeloma
MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: DARZALEX
Product Name: Daratumumab
Product Code: HuMax-CD38
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DARATUMUMAB
CAS Number: 945721-28-8
Current Sponsor code: JNJ-54767414 (Daratumumab)
Other descriptive name: HUMAX-CD38
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Product Name: Daratumumab co-formulated with recombinant human hyaluronidase (rHuPH20)
Product Code: JNJ-54767414
Pharmaceutical Form: Solution for injection
INN or Proposed INN: DARATUMUMAB
CAS Number: 945721-28-8
Current Sponsor code: JNJ-54767414
Other descriptive name: HuMax-CD38, 3003-005
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 120-

Primary Outcome(s)

Primary end point(s): The primary endpoint is PFS, which is defined as the duration from the date of randomization to either progressive disease or death, whichever comes first. Disease progression will be determined according to the IMWG criteria. For subjects who have not progressed and are alive, data will be censored at the last disease evaluation before the start of any subsequent anti-myeloma therapy. Relapse from CR by positive immunofixation or trace amount of M-protein is not considered to be progressive disease and is not included in the PFS calculation.
As the superiority of daratumumab combined with VMP over VMP alone with respect to PFS was established at the second interim analysis, the interim PFS analysis will serve as the primary PFS analysis, which otherwise was to occur when approximately 360 PFS events had been observed.

Secondary Objective: The secondary objectives are:
? To determine if the addition of daratumumab to VMP will improve clinical outcome as measured by:
? Time to disease progression (TTP)
? CR rate
? Minimal residual disease (MRD) negativity rate
? PFS2 (defined as time from randomization to progression on the next line of therapy or death, whichever comes first)
? Time to next treatment
? Overall response rate (partial response [PR] or better)
? Stringent CR (sCR) rate
? Very good partial response (VGPR) or better rate
? Time to response
? Duration of response
? Overall survival
? To assess patient reported outcomes and heath economic/resource utilization
? To determine the pharmacokinetics and immunogenicity of daratumumab in all subjects and the immunogenicity of recombinant human hyaluronidase PH20(rHuPH20) in subjects receiving daratumumab SC
? To assess the safety and tolerability of daratumumab when administered in combination with VMP
Please see protocol for a full list of objectives.

Main Objective: The primary objective is to determine if the addition of daratumumab to VMP will prolong PFS compared with VMP.

Timepoint(s) of evaluation of this end point: Assess at approximately 41 months from randomization

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - For secondary end points 1-4, 6-9 = Assess at approximately 41 months from randomization
- For secondary end points 5 = Week 58, 84, and 110
- For secondary end points 10 = Assess at approximately 41 months after first patient randomized up to a maximum of 5 years after last participant is dosed

Secondary end point(s): ? Time to disease progression (TTP) is defined as the time from the date of randomization to the date of first documented evidence of PD, as defined in the IMWG criteria. For subjects who have not progressed, data will be censored at the date of the disease evaluation before the start of any subsequent anti-myeloma therapy.
? CR rate, defined as the percentage of subjects achieving CR, as defined by:
- Negative immunofixation of serum and urine, and
- Disappearance of any soft tissue plasmacytomas, and
- <5% PCs in bone marrow
- For those subjects with negative or low SPEP (=0.2 g/L) and suspected daratumumab interference on immunofixation, a reflex assay using anti-idiotype antibody will be utilized to confirm daratumumab interference and rule out false positive immunofixation. Subjects who have confirmed daratumumab interference, but meet all other clinical criteria for CR or sCR, will be considered CR/sCR.
? MRD negativity rate, defined as the proportion of subjects who have negative MRD at any time point after the date of randomization.
? Progression-free Survival on Next line of Therapy (PFS2), defined as the time from randomization to progression on the next line of treatment or death, whichever comes first. Disease progression will be based on investigator judgment. Subjects who are still alive and not yet progressed on the next line of treatment will be censored on the last date of follow-up.
? Time to next treatment, defined as the time from randomization to the start of the next-line treatment.
? Overall response rate (ORR), defined as the proportion of subjects who achieve PR or better, according to the IMWG criteria, during or after the study treatment.
? sCR rate, defined as the percentage of subjects achieving CR in addition to having a normal FLC ratio and an absence of clonal cells in bone marrow by immunohistochemistry, immunofluorescence, 2-4 color flow cytometry.
? Proportion of subjects who achieve VGPR or better, defined as the proportion of subjects achieving VGPR and CR (including sCR) according to the IMWG criteria during or after the study treatment at the time of data cutoff.
? Time to response, defined as the time between randomization and the first efficacy evaluation that the subject has met all criteria for PR or better. For subjects without response, data will be censored either at the date of progressive disease or, in the absence of progressive disease, at the last disease evaluation before the start of subsequent antimyeloma therapy.
? Duration of response, calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria. For subjects who have not progressed, data will be censored at the last disease evaluation before the start of any subsequent antimyeloma therapy.
? OS, measured from the date of randomization to the date of the subject's death. If the subject is alive or the vital status is unknown, then the subject's data will be censored at the date the subject was last known to be alive.
? Impact of D-VMP compared to VMP on patient-reported perception of global health.
? Clinical efficacy of D-VMP in high risk molecular subgroups compared to VMP alone.
? Summary of subject's preference of route of treatment administration.

Secondary ID(s)

2014-002272-88-HU

54767414MMY3007

Source(s) of Monetary Support

Janssen Research & Development, LLC

Ethics review

Status: Approved
Approval date: 02/12/2014
Contact: