Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
drksid header

  DRKS00007830

Trial Description

start of 1:1-Block title

Title

A Phase 3 Study Comparing Daratumumab, Lenalidomide, and Dexamethasone (DRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High Dose Therapy

end of 1:1-Block title
start of 1:1-Block acronym

Trial Acronym

[---]*

end of 1:1-Block acronym
start of 1:1-Block url

URL of the Trial

[---]*

end of 1:1-Block url
start of 1:1-Block public summary

Brief Summary in Lay Language

The purpose of this study is to compare the efficacy of daratumumab in combination with
lenalidomide and dexamethasone to that of lenalidomide and dexamethasone in terms of
progression-free survival (PFS) in participants with newly diagnosed multiple myeloma (a
blood cancer of plasma cells) who are not candidates for high dose chemotherapy (treatment
of disease, usually cancer, by chemical agents) and autologous stem cell transplant (ASCT).

end of 1:1-Block public summary
start of 1:1-Block scientific synopsis

Brief Summary in Scientific Language

This is a Phase 3, randomized (study drug assigned by chance), open-label (participants and
researchers are aware about the treatment, participants are receiving), active-controlled
(study in which the experimental treatment or procedure is compared to a standard treatment
or procedure), parallel-group (each group of participants will be treated at the same time),
and multicenter (when more than one hospital or medical school team work on a medical
research study) study in participants with newly diagnosed multiple myeloma and who are not
candidates for high dose chemotherapy and ASCT. All the eligible participants will be
randomly assigned to receive either daratumumab in combination with lenalidomide and
dexamethasone (DRd) or lenalidomide and dexamethasone (Rd). Daratumumab (16 milligram per
kilogram [mg/kg]) will be administered weekly for first 8 weeks (Cycles 1 to 2) of treatment
and then every other week for 16 weeks (Cycles 3 to 6), then every 4 weeks (from Cycle 7 and
beyond) until progression of disease or unacceptable toxicity. Lenalidomide will be
administered at a dose of 25 mg orally on Days 1 through 21 of each 28-day cycle, and
dexamethasone will be administered at a dose of 40 mg once a week for both treatment arms.
Participants in the DRd arm will receive lenalidomide/dexamethasone for a maximum of 2 years
(participants will continue to receive dexamethasone as a premedication for daratumumab
administration even after the lenalidomide/dexamethasone treatment is discontinued); those
in the Rd arm will continue lenalidomide/dexamethasone until disease progression or
unacceptable toxicity.The study consists of 3 phases: Screening Phase (within 21 days prior
to the first dose administration on Day 1), Treatment Phase (Day 1 up to discontinuation of
all study treatment), and Follow-up Phase (from discontinuation of all study treatment up to
death, lost to follow up, consent withdrawal, or study end, whichever occurs first). The
maximum duration of study will be 5 years after last participant is randomized. Efficacy
will primarily be evaluated by PFS. Participants' safety will be monitored throughout the
study.

end of 1:1-Block scientific synopsis
start of 1:1-Block forwarded Data

Do you plan to share individual participant data with other researchers?

[---]*

end of 1:1-Block forwarded Data
start of 1:1-Block forwarded Data Content

Description IPD sharing plan:

[---]*

end of 1:1-Block forwarded Data Content
start of 1:1-Block organizational data

Organizational Data

  •   DRKS00007830
  •   2015/10/21
  •   2014/08/11
  •   no
  •   [---]*
  •   [---]*
end of 1:1-Block organizational data
start of 1:n-Block secondary IDs

Secondary IDs

  •   2014-002273-11 
  •   NCT02252172  (ClinicalTrials.gov)
  •   CR104762  (Janssen Research & Development, LLC)
  •   54767414MMY3008 
  •   2014-002273-11 
end of 1:n-Block secondary IDs
start of 1:N-Block indications

Health Condition or Problem studied

  •   Multiple Myeloma
  •   C90.0 -  Multiple myeloma
end of 1:N-Block indications
start of 1:N-Block interventions

Interventions/Observational Groups

  •   Drug: Daratumumab
  •   Drug: Lenalidomide
  •   Drug: Dexamethasone
  •   Drug: Lenalidomide
  •   Drug: Dexamethasone
end of 1:N-Block interventions
start of 1:1-Block design

Characteristics

  •   Interventional
  •   [---]*
  •   Randomized controlled trial
  •   Open (masking not used)
  •   [---]*
  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   III
  •   [---]*
end of 1:1-Block design
start of 1:1-Block primary endpoint

Primary Outcome

- Progression-Free Survival (PFS) Time; time frame: From baseline for the duration of disease follow-up, with an expected average of 40 months; The PFS is defined as time from date of randomization to either progressive disease (PD), or death, whichever occurs first. PD will be determined according to International Myeloma Working Group (IMWG) criteria.

end of 1:1-Block primary endpoint
start of 1:1-Block secondary endpoint

Secondary Outcome

- Time to Disease Progression (TTP); time frame: From baseline for the duration of disease follow-up, with an expected average of 40 months; The TTP is defined as time from date of randomization to date of first documented evidence of PD, as defined by IMWG criteria.
- Percentage of Participants With Stringent Complete Response (sCR); time frame: From baseline for the duration of disease follow-up, with an expected average of 40 months; Percentage of participants with sCR, as defined by the IMWG criteria, will be reported.
- Percentage of Participants With Complete response (CR); time frame: From baseline for the duration of disease follow-up, with an expected average of 40 months; Percentage of participants with CR, as defined by the IMWG criteria, will be reported.
- Progression-Free Survival on Next Line of Therapy (PFS2); time frame: From baseline for the duration of disease follow-up, with an expected average of 40 months; The PFS2 is defined as time from randomization to progression on next line of treatment or death, whichever occur first. Disease progression will be based on Investigator judgment.
- Percentage of Participants With Negative Minimal Residual Disease (MRD); time frame: From baseline up to 18 months after confirmed CR, with an expected average of 24 months; The MRD assessment will be done by next-generation sequencing (NGS) in both blood and bone marrow aspirate in participants who achieve CR/sCR, at 6, 12 and 18 months after confirmed CR.
- Time To Next Treatment; time frame: From baseline for the duration of disease follow-up, with an expected average of 40 months; Time to next treatment is defined as the time from randomization to the start of next-line treatment.
- Percentage of Participants With Overall Response (OR); time frame: From baseline for the duration of disease follow-up, with an expected average of 40 months; Overall response (OR) is defined as achieving CR or partial response (PR), according to the IMWG criteria.
- Percentage of Participants With Very Good Partial Response (VGPR) or Better Response; time frame: From baseline for the duration of disease follow-up, with an expected average of 40 months; Percentage of participants with VGPR or better response (who achieve VGPR and CR [including a sCR]) according to IMWG criteria will be reported.
- Duration of Response (DR); time frame: From baseline for the duration of disease follow-up, with an expected average of 40 months; The DR is time from date of initial documentation of response (CR or PR) to date of first documented PD, as defined by IMWG criteria.
- Overall Survival (OS) Time; time frame: Baseline up to 5 years after last participant is randomized; The OS is the time from date of randomization to date of participant's death.
- European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score; time frame: From baseline up to 16 weeks after disease progression, with an expected average of 44 months; The EORTC QLQ-C30 includes 30 items resulting in 5 functional scales (physical, role, cognitive, emotional, and social), 1 global health status scale, 3 symptom scales (fatigue, pain, nausea/vomiting) and 6 single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties).
- Euro Quality of Life (EQ-5D-5L) Health State Profile Utility Score; time frame: From baseline up to 16 weeks after disease progression, with an expected average of 44 months; Participant rated questionnaire to assess health-related quality of life in terms of a single utility score. EQ-5D-5L assesses level of current health by assessing 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression plus a visual analog scale rating "health today".

end of 1:1-Block secondary endpoint
start of 1:n-Block recruitment countries

Countries of Recruitment

  •   United States
  •   Australia
  •   Austria
  •   Canada
  •   Denmark
  •   France
  •   Germany
  •   Ireland
  •   Israel
  •   Netherlands
  •   New Zealand
  •   Sweden
  •   United Kingdom
end of 1:n-Block recruitment countries
start of 1:n-Block recruitment locations

Locations of Recruitment

  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
  •  
end of 1:n-Block recruitment locations
start of 1:1-Block recruitment

Recruitment

  •   [---]*
  •   2015/02/27
  •   730
  •   Multicenter trial
  •   International
end of 1:1-Block recruitment
start of 1:1-Block inclusion criteria

Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
end of 1:1-Block inclusion criteria
start of 1:1-Block inclusion criteria add

Additional Inclusion Criteria

- Participant must have documented multiple myeloma and measurable disease defined as:
1) monoclonal plasma cells in the bone marrow greater than or equal to (>=) 10
percent (%) or presence of a biopsy proven plasmacytoma; 2) measurable disease as
defined by any of the following: (a) immunoglobulin (Ig) G myeloma (serum monoclonal
paraprotein [M-protein] level >=1.0 gram/deciliter [g/dL] or urine M-protein level
>=200 milligram[mg]/24 hours[hrs]; or (b) IgA, IgM, IgD, or IgE multiple myeloma
(serum M-protein level >=0.5 g/dL or urine M-protein level >=200 mg/24 hrs); or (c)
light chain multiple myeloma (serum immunoglobulin free light chain >=10 mg/dL and
abnormal serum immunoglobulin kappa lambda free light chain ratio)

- Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status
score of 0, 1, or 2

- Participants who are newly diagnosed and not considered for high-dose chemotherapy
due to: being age >=65 years; or participants less than (<) 65 years with presence of
important comorbid condition(s) likely to have a negative impact on tolerability of
high dose chemotherapy with stem cell transplantation. Sponsor review and approval of
participants below 65 years of age is required before randomization

- Women of childbearing potential must commit to either abstain continuously from
sexual intercourse or to use 2 methods of reliable birth control simultaneously as
deemed appropriate by the Investigator. Contraception must begin 4 weeks prior to
dosing

- Man, who is sexually active with a woman of child-bearing potential and has not had a
vasectomy, must agree to use an adequate contraception method as deemed appropriate
by the Investigator, and must also agree to not donate sperm during the study and for
4 weeks after last dose of lenalidomide and 4 months after last dose of daratumumab

end of 1:1-Block inclusion criteria add
start of 1:1-Block exclusion criteria

Exclusion Criteria

- Participant has a diagnosis of primary amyloidosis, monoclonal gammopathy of
undetermined significance (presence of serum M-protein <3 g/dL; absence of lytic bone
lesions, anemia, hypercalcemia, and renal insufficiency related to the M-protein), or
smoldering multiple myeloma (asymptomatic multiple myeloma with absence of related
organ or tissue impairment end organ damage)

- Participant has a diagnosis of Waldenström'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 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 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 5 years)

- 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 a maximum 4 days) of corticosteroids before treatment

- Participant has had radiation therapy within 14 days of randomization

- Participant has known chronic obstructive pulmonary disease (COPD) (defined as a
forced expiratory volume in 1 second [FEV1] <60% of predicted normal), persistent
asthma, or a history of asthma within the last 2 years (intermittent asthma is
allowed). Participants with known or suspected COPD or asthma must have a FEV1 test
during Screening

- Participant is known to be seropositive for history of human immunodeficiency virus
(HIV) or known to have active hepatitis B or hepatitis C

end of 1:1-Block exclusion criteria
start of 1:n-Block addresses

Addresses

  • start of 1:1-Block address primary-sponsor
    • Janssen Research & Development, LLC
    end of 1:1-Block address primary-sponsor
    start of 1:1-Block address contact primary-sponsor
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact primary-sponsor
  • start of 1:1-Block address scientific-contact
    • Janssen Research & Development, LLC
    • Janssen Research & Development, LLC Clinical Trial 
    end of 1:1-Block address scientific-contact
    start of 1:1-Block address contact scientific-contact
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact scientific-contact
  • start of 1:1-Block address public-contact
    • Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: 
    end of 1:1-Block address public-contact
    start of 1:1-Block address contact public-contact
    end of 1:1-Block address contact public-contact
end of 1:n-Block addresses
start of 1:n-Block material support

Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
    end of 1:1-Block address materialSupport
    start of 1:1-Block address contact materialSupport
    •   [---]*
    •   [---]*
    •   [---]*
    •   [---]*
    end of 1:1-Block address contact materialSupport
end of 1:n-Block material support
start of 1:1-Block state

Status

  •   Recruiting ongoing
  •   [---]*
end of 1:1-Block state
start of 1:n-Block publications

Trial Publications, Results and other Documents

end of 1:n-Block publications
The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   2
  •   2015/08/05
* This entry means the parameter is not applicable or has not been set.