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Trial record 1 of 1 for:    NCT03993912
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Compare Lenalidomide and Subcutaneous Daratumumab vs Lenalidomide and Dexamethasone in Frail Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High Dose Therapy (IFM2017_03)

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ClinicalTrials.gov Identifier: NCT03993912
Recruitment Status : Recruiting
First Posted : June 21, 2019
Last Update Posted : December 4, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Lille

Tracking Information
First Submitted Date  ICMJE May 27, 2019
First Posted Date  ICMJE June 21, 2019
Last Update Posted Date December 4, 2019
Actual Study Start Date  ICMJE October 17, 2019
Estimated Primary Completion Date October 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2019)
Comparison of the efficacy of Daratumumab SC injection when combined with Lenalidomide (R-Dara SC) vs Lenalidomide and Dexamethasone (Rd): PFS [ Time Frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months ]
The primary objective is to compare the efficacy of Daratumumab SC injection when combined with Lenalidomide (R-Dara SC) to that of Lenalidomide and Dexamethasone (Rd), in terms of PFS in frail subjects with newly diagnosed myeloma who are not candidates for high dose chemotherapy and autologous stem cell transplant.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2019)
  • Time-to-treatment failure [ Time Frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months ]
  • Time-to-next treatment [ Time Frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months ]
  • PFS2 time [ Time Frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months ]
  • Overall survival (OS) time [ Time Frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 84months ]
    Overall survival (OS) time,
  • Complete remission (CR) [ Time Frame: From date of randomization until the date of first documented progression whichever came first, assessed up to 84months ]
    Percentage of participants with CR, as defined by the IMWG criteria, will be reported.
  • Very good partial response (VGPR) or better. [ Time Frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months ]
    VGPR or better, defined as VGPR or CR according to the IMWG criteria during or after the study treatment at the time of data cutoff.
  • Overall response (CR + VGPR + partial response [PR]). [ Time Frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months ]
    Overall response, defined as CR or VGPR or PR, according to the IMWG criteria
  • Occurrence of grade 3 or more side effects. [ Time Frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months ]
    Collecting all AE (grade 3 or more)
  • Safety and tolerability of Daratumumab SC when administered in combination with Revlimid: NCI-CTCAE V5.0. [ Time Frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months ]
    Evaluation of safety data by type, frequency, severity, relation to study drug, according to NCI-CTCAE V5.0.
  • Evaluation of quality of life based on MY20 questionnaires [ Time Frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months ]
    Treatment effects on patient reported outcomes and heath economic/resource utilization.
  • Evaluation of quality of life based on EORTC C30 questionnaires [ Time Frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months ]
    Treatment effects on patient reported outcomes and heath economic/resource utilization.
  • Evaluation of quality of life based on EQ-5D questionnaires [ Time Frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months ]
    Treatment effects on patient reported outcomes and heath economic/resource utilization.
  • Minimal residual disease (MRD) negative rate at 12 months. [ Time Frame: after 12 months of treatment ]
    Proportion of participants assessed as MRD negative
  • Event Free Survival [ Time Frame: From date of randomization until the date of first documented progression or date of toxicity or date of death from any cause, whichever came first, assessed up to 84months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Compare Lenalidomide and Subcutaneous Daratumumab vs Lenalidomide and Dexamethasone in Frail Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High Dose Therapy
Official Title  ICMJE A Phase III Study Comparing Lenalidomide and Subcutaneous Daratumumab (R-Dara SC) vs Lenalidomide and Dexamethasone (Rd) in Frail Subjects With Previously Untreated Multiple Myeloma Who Are Ineligible for High Dose Therapy
Brief Summary 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 team work on a medical research study) study in participants with newly diagnosed multiple myeloma (a blood cancer of plasma cells) and who are not candidates for high dose chemotherapy (treatment of disease, usually cancer, by chemical agents) and autologous stem cell transplant (ASCT). The primary hypothesis of this study is that subcutaneous Daratumumab in combination with Lenalidomide will prolong progression-free survival and likely induce less toxicity as compared with Lenalidomide and dexamethasone, in elderly frail subjects with newly diagnosed Multiple myeloma who are ineligible for high dose chemotherapy and ASCT
Detailed Description The primary hypothesis of this study is that subcutaneous Daratumumab in combination with Lenalidomide will prolong progression-free survival and likely induce less toxicity as compared with Lenalidomide and dexamethasone, in elderly frail subjects with newly diagnosed Multiple myeloma who are ineligible for high dose chemotherapy and ASCT
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Daratumumab SC in combination with Lenalidomide

    Daratumumab SC 1800 mg

    • once every week for 8 weeks
    • then once every other week for 16 weeks
    • thereafter once every 4 weeks, until progression
  • Drug: Lenalidomide PO (25mg)
    Lenalidomide PO (25mg): days 1 through 21 of each 28-day cycle, until progression
  • Drug: Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression
    Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression
Study Arms  ICMJE
  • Experimental: Arm 1: Experimental group

    Daratumumab SC 1800 mg

    • once every week for 8 weeks
    • then once every other week for 16 weeks
    • thereafter once every 4 weeks, until progression Lenalidomide PO (25mg): days 1 through 21 of each 28-day cycle, until progression Dexamethasone PO (20mg): days 1, 8, 15, 22 of a 28-day cycle, for the first 2 cycles, then discontinued
    Interventions:
    • Drug: Daratumumab SC in combination with Lenalidomide
    • Drug: Lenalidomide PO (25mg)
    • Drug: Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression
  • Sham Comparator: Arm 2: Control group
    Lenalidomide PO (25mg): days 1 through 21 of each 28-day cycle, until progression Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression
    Interventions:
    • Drug: Lenalidomide PO (25mg)
    • Drug: Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 20, 2019)
294
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2027
Estimated Primary Completion Date October 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subject must be at least 65 years of age.
  2. Subject must have documented multiple myeloma satisfying the CRAB criteria and measurable disease.
  3. Newly diagnosed and not considered candidate for high-dose chemotherapy with SCT.
  4. Subject must have a Frailty Score ≥ 2
  5. Subject must have within 5 days prior to first drug intake (C1D1) pretreatment clinical laboratory values meeting the following criteria during the Screening Phase:

    • hemoglobin ≥7.5 g/dL
    • absolute neutrophil count ≥1.0 x 109/L
    • platelet count ≥70 x 109/L
    • aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN)
    • alanine aminotransferase (ALT) ≤2.5 x ULN
    • total bilirubin ≤2.0 x ULN
    • creatinine clearance≥30mL/min
  6. Measurable ISS with β2-microglobulin and albumin values for randomization
  7. A man who is sexually active with a woman of childbearing potential must agree to use a latex or synthetic condom, even if they had a successful vasectomy. All men must also not donate sperm during the study, for 4 weeks after the last dose of lenalidomide, and for 4 months after the last dose of daratumumab. Women participating in this study must be postmenopausal.
  8. Each subject 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. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, as referenced in the ICF.
  9. Subjects affiliated with an appropriate social security system.

Exclusion Criteria:

  1. Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma.
  2. Subject 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.
  3. Subject has prior or current systemic therapy or SCT for multiple myeloma
  4. Subject has a history of malignancy (other than multiple myeloma) within 5 years before the date of randomization
  5. Subject has had radiation therapy within 14 days of randomization.
  6. Subject has had plasmapheresis within 28 days of randomization.
  7. Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma.
  8. Subject has known chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume [FEV] in 1 second <60% of predicted normal), persistent asthma, or a history of asthma within the last 2 years (intermittent asthma is allowed).
  9. Subject is known to be seropositive for history of human immunodeficiency virus (HIV)
  10. Seropositive for hepatitis B.
  11. (Known to be) seropositive for hepatitis C
  12. Subject has any concurrent medical or psychiatric condition or 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.
  13. Subject has clinically significant cardiac disease, including:

    • myocardial infarction within 1 year before randomization, or an unstable or uncontrolled disease/condition related to or affecting cardiac function
    • uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities
    • screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec
  14. Subject has known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients
  15. Subject has plasma cell leukemia or POEMS syndrome
  16. Subject is known or suspected of not being able to comply with the study protocol. Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject or that could prevent, limit, or confound the protocol-specified assessments.
  17. Subject has had major surgery within 2 weeks before randomization or has not fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study.
  18. Subject has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 4 weeks before randomization or is currently enrolled in an interventional investigational study.
  19. Refusal to consent or protected by legal regime ( guardianship, trusteeship)
  20. Subject has contraindications to required prophylaxis for deep vein thrombosis and pulmonary embolism
  21. Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Thierry Facon, MD,PhD 3.20.44.57.12 ext +33 thierry.facon@chru-lille.fr
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03993912
Other Study ID Numbers  ICMJE 2018_16
2018-003535-30 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital, Lille
Study Sponsor  ICMJE University Hospital, Lille
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Thierry Facon, MD,PhD University Hospital, Lille
PRS Account University Hospital, Lille
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP