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Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Participants With Previously Untreated Multiple Myeloma

This study is currently recruiting participants.
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Verified June 2017 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT02252172
First received: August 11, 2014
Last updated: June 20, 2017
Last verified: June 2017
  Purpose
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).

Condition Intervention Phase
Multiple Myeloma Drug: Daratumumab Drug: Lenalidomide Drug: Dexamethasone Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) Time [ Time Frame: From baseline for the duration of disease follow-up, with an expected average of 51 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.


Secondary Outcome Measures:
  • Time to Disease Progression (TTP) [ Time Frame: From baseline for the duration of disease follow-up, with an expected average of 51 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 Complete response (CR) [ Time Frame: From baseline for the duration of disease follow-up, with an expected average of 24 months ]
    Percentage of participants with CR, as defined by the IMWG criteria, will be reported.

  • Minimal Residual Disease (MRD) Negativity Rate [ Time Frame: From baseline to 30 months post C1D1 with an expected average of 24 months ]
    MRD negativity rate, defined as the proportion of participants assessed as MRD negative, at any timepoint after the date of randomization.

  • 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 51 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.

  • Overall Survival (OS) Time [ Time Frame: Baseline up to 7 years after last participant is randomized ]
    The OS is the time from date of randomization to date of participant's death.

  • Percentage of Participants With Stringent Complete Response (sCR) [ Time Frame: From baseline for the duration of disease followup, with an expected average of 24 months ]
    Percentage of participants with sCR, as defined by the IMWG criteria, will be reported.

  • Time To Next Treatment [ Time Frame: From baseline for the duration of disease followup, with an expected average of 51 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 followup, with an expected average of 24 months ]
    Overall response (OR) is defined as achieving CR or partial response (PR) or better, 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 followup, with an expected average of 24 months ]
    Percentage of participants with VGPR or better response (who achieve VGPR and CR [including a sCR]) according to IMWG criteria will be reported.

  • Time to Response [ Time Frame: From baseline for the duration of disease to follow-up, with an expected average of 24 months ]
    Time to response is defined as the time between the randomization and the first efficacy evaluation that the participant has met all criteria for PR or better.

  • Duration of Response (DR) [ Time Frame: From baseline for the duration of disease followup, with an expected average of 51 months ]
    The DR is time from date of initial documentation of response (PR or better) to date of first documented PD, as defined by IMWG criteria.

  • 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 67 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 67 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".


Estimated Enrollment: 730
Actual Study Start Date: February 16, 2015
Estimated Study Completion Date: November 22, 2022
Estimated Primary Completion Date: December 22, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Daratumumab + Lenalidomide + Dexamethasone (DRd)
Participants will receive Daratumumab 16 milligram per kilogram (mg/kg) by intravenous infusion, once a week for 8 weeks, then once every other week for 16 weeks, thereafter once every 4 weeks until documented progression of disease, unacceptable toxicity, or end of study (maximum up to 7 years). Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle, until disease progression or unacceptable toxicity, and Dexamethasone 40 mg orally or intravenously once a week until disease progression or unacceptable toxicity, whichever comes first.
Drug: Daratumumab
Daratumumab will be administered at a dose of 16 milligram per kilogram (mg/kg) by intravenous infusion, once a week for 8 weeks, then once every other week for 16 weeks, thereafter once every 4 weeks until documented progression of disease, unacceptable toxicity, or end of study (maximum up to 7 years).
Other Name: JNJ-54767414
Drug: Lenalidomide
Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle.
Drug: Dexamethasone
Dexamethasone 40 mg orally or intravenously once in a week.
Active Comparator: Lenalidomide and Dexamethasone (Rd)
Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle, until the disease progression or unacceptable toxicity and Dexamethasone 40 mg orally or intravenously once a week until disease progression or unacceptable toxicity, or end of study (maximum up to 7 years).
Drug: Lenalidomide
Lenalidomide 25 mg capsule orally on Day 1 through Day 21 of each 28-day cycle.
Drug: Dexamethasone
Dexamethasone 40 mg orally or intravenously once in a week.

Detailed Description:
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 both treatment arms will continue lenalidomide and dexamethasone until disease progression or unacceptable toxicity. Participants in Arm B (Rd) who had discontinued treatment with Rd at 24 months may re-start treatment. 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 7 years after last participant is randomized. Efficacy will primarily be evaluated by PFS. Participants' safety will be monitored throughout the study.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant must have documented multiple myeloma satisfying the CRAB (calcium elevation, renal insufficiency, anemia and bone abnormalities) criteria, monoclonal plasma cells in the bone marrow greater than or equal to (>=) 10 percent (%) or presence of a biopsy proven plasmacytoma and 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 without measurable disease in serum or urine (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 and must continue for 3 months after the last dose of daratumumab
  • Man, who is sexually active with a woman of child-bearing potential potential must agree to use a latex or synthetic condom, even if he had a successful 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

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 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] <50% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (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) or hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg] or antibodies to hepatitis B surface and core antigens [anti-HBs and anti-HBc, respectively]) or hepatitis C (anti-HCV antibody positive or HCV-ribonucleic acid [RNA] quantitation positive)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02252172

Contacts
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: JNJ.CT@sylogent.com

  Show 266 Study Locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02252172     History of Changes
Other Study ID Numbers: CR104762
54767414MMY3008 ( Other Identifier: Janssen Research & Development, LLC )
2014-002273-11 ( EudraCT Number )
Study First Received: August 11, 2014
Last Updated: June 20, 2017

Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:
Multiple Myeloma
Daratumumab
JNJ-54767414
Lenalidomide
Dexamethasone

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lenalidomide
Thalidomide
Antibodies, Monoclonal
Daratumumab
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents

ClinicalTrials.gov processed this record on June 26, 2017