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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)

U

University Hospital, Lille

Status and phase

Active, not recruiting
Phase 3

Conditions

Multiple Myeloma

Treatments

Drug: Lenalidomide PO (25mg)
Drug: Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression
Drug: Daratumumab SC in combination with Lenalidomide

Study type

Interventional

Funder types

Other

Identifiers

NCT03993912
2018-003535-30 (EudraCT Number)
2018_16

Details and patient eligibility

About

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

Full 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

Enrollment

294 estimated patients

Sex

All

Ages

65+ years old

Volunteers

No Healthy Volunteers

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.

  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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

294 participants in 2 patient groups

Arm 1: Experimental group
Experimental group
Description:
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
Treatment:
Drug: Daratumumab SC in combination with Lenalidomide
Drug: Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression
Drug: Lenalidomide PO (25mg)
Arm 2: Control group
Sham Comparator group
Description:
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
Treatment:
Drug: Dexamethasone PO (20mg): days 1, 8, 15, 22 of each 28-day cycle, until progression
Drug: Lenalidomide PO (25mg)

Trial contacts and locations

23

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Data sourced from clinicaltrials.gov

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