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

Phase 1

• Conditions: Multiple myeloma; MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-002273-11-DE
• Lead Sponsor: Janssen-Cilag International N.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-05-04
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 730

Inclusion Criteria

1. Subject must be at least 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place).
2.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 measurabl. Measurable disease, as assessed by central laboratory, defined by any of the following:
- immunoglobulin (Ig) G myeloma (serum monoclonal paraprotein
[Mprotein] level >=1.0 gram/deciliter [g/dL] or urine Mprotein level
>=200 milligram[mg]/24 hours[hrs]; or
- IgA, IgM, IgD, or IgE multiple myeloma (serum Mprotein level >=0.5
g/dL or urine Mprotein level >=200 mg/24 hrs); or - 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)
3.Newly diagnosed and not considered candidate for high-dose chemotherapy with SCT due to:
? Being age =65 years, OR
? In subjects <65 years: 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 subjects under 65 years of age is required before randomization.
4.Subject must have an ECOG performance status score of 0, 1, or 2
5.Subject must have pretreatment clinical laboratory values meeting the following criteria during the Screening Phase:
a) hemoglobin ?7.5 g/dL (?? mM/L; prior red blood cell [RBC]
transfusion or recombinant human erythropoietin use is permitted);
b) absolute neutrophil count ?1.0 x 109/L (granulocyte colony
stimulating factor [GCSF] use is permitted);
c) platelet count ?70 x 109/L for subjects in whom <50% of bone
marrow nucleated cells are plasma cells; otherwise platelet count >50 × 109/L (transfusions are not permitted to achieve this minimum platelet count);
d) aspartate aminotransferase (AST) =2.5 x upper limit of normal (ULN);
e) alanine aminotransferase (ALT) =2.5 x ULN;
f) total bilirubin =2.0 x ULN, except in subjects with congenital
bilirubinemia, such as Gilbert syndrome (direct bilirubin =2.0 x ULN);
g) Creatinine clearance =30 mL/min (for lenalidomide dose adjustment for subjects with creatinine clearance 30-50 mL/min. Creatinine clearance can be calculated using the Cockcroft-Gault formula; or for subjects with over- or underweight, creatinine clearance may be measured from a 24-hours urine collection using the formula
h) corrected serum calcium =14 mg/dL (=3.5 mM/L); or free ionized
calcium =6.5 mg/dL (=1.6 mM/L)
6. Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for subjects participating in clinical studies. 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 [IUD], hormonal [progesterone-only birth control pills or injections or partner's vasectomy) and one additional effective contraceptive method (male latex or synthetic condom, diaphragm, or cervical cap). Contraception must begin 4 weeks prior to dosing and must continue for 3 months after the last dose of daratumumab. Reliable contraception is indi

Exclusion Criteria

1.Subject has a diagnosis of primary amyloidosis, monoclonal
gammopathy of undetermined significance, or smoldering multiple
myeloma. Monoclonal gammopathy of undetermined significance is
defined by presence of serum M-protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the Mprotein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less. Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage
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, with the exception of an emergency use of a short course
(equivalent of dexamethasone 40 mg/day for 4 days) of corticosteroids before treatment.
4. Subject 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)
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.a) Subject has known chronic obstructive pulmonary disease (COPD) with a Forced Expiratory Volume in 1 second (FEV1) <50% of predicted normal. Note that FEV1 testing is required for subjects suspected of having COPD and subjects must be excluded if FEV1 <50% of predicted normal.
8.b) Subject has had known moderate or severe persistent asthma
within the last 2 years or currently has uncontrolled asthma of any
classification (Note that subjects who currently have controlled
intermittent asthma or controlled mild persistent asthma are allowed in the study).
9. Subject 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-RNA quantitation positive).
10. Subject has any concurrent medical or psychiatric condition or
disease (eg, 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.
11. 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 (eg, unstable angina, congestive heart failure, New York Heart Association Class III-IV
? uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 4 Grade = 3) or clinically significant ECG abnormalities
? screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia's formula (QTcF) >470 msec
12. Subject has known allergies, hypersensitivity, or intolerance to
corticoste

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified