Isatuximab in Combination With Lenalidomide and Dexamethasone in High-risk Smoldering Multiple Myeloma

  • STATUS
    Recruiting
  • End date
    Oct 20, 2033
  • participants needed
    323
  • sponsor
    Sanofi
Updated on 20 June 2021
bone marrow procedure
dexamethasone
lenalidomide
neutrophil count
smoldering myeloma
bone marrow plasma cells

Summary

Primary Objectives:

  • Safety run-in: To confirm the recommended dose of isatuximab when combined with lenalidomide and dexamethasone in participants with high-risk smoldering multiple myeloma (SMM)
  • Randomized Phase 3: To demonstrate the clinical benefit of isatuximab in combination with lenalidomide and dexamethasone in the prolongation of progression-free survival when compared to lenalidomide and dexamethasone in participants with high-risk SMM

Secondary Objectives:

Safety run-in

  • To assess overall response rate (ORR)
  • To assess duration of response (DOR)
  • To assess minimal residual disease (MRD) negativity in participants achieving very good partial response (VGPR) or complete response (CR)
  • To assess time to diagnostic (SLiM CRAB) progression or death
  • To assess time to first-line treatment for multiple myeloma (MM)
  • To assess the potential immunogenicity of isatuximab
  • Impact of abnormal cytogenetic subtype

Randomized Phase 3 - Key Secondary Objectives:

To compare between the arms

  • MRD negativity
  • Sustained MRD negativity
  • Second progression-free survival (PFS2)
  • Overall survival

Other Secondary Objectives:

To evaluate in both arms

  • CR rate
  • ORR
  • DOR
  • Time to diagnostic (SLiM CRAB) progression
  • Time to first-line treatment for MM
  • Safety and tolerability
  • Pharmacokinetics (PK)
  • Potential of isatuximab immunogenicity
  • Clinical outcome assessments (COAs)

Description

Study duration is expected to be approximately 10 years, including a 28-day screening period, followed by an up to 36-month treatment period, and a follow-up period of approximately 7 years.

Details
Condition Multiple Myeloma, Lymphoproliferative Disorder, Lymphoproliferative disorders, multiple myeloma (mm)
Treatment Dexamethasone, Lenalidomide, isatuximab SAR650984
Clinical Study IdentifierNCT04270409
SponsorSanofi
Last Modified on20 June 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Participants who are diagnosed within 5 years with SMM (per International Myeloma Working Group [IMWG] criteria), defined as serum M-protein 30 g/L or urinary M-protein 500 mg per 24 hour or both, and/or clonal bone marrow plasma cells (BMPCs) 10% to <60%, and absence of myeloma defining events or other related conditions and with high-risk SMM
Participant must be at least 18 years of age inclusive or older
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 or 2
Capable of giving voluntary written informed consent
Absolute neutrophil count (ANC) 1000/L (1 109/L)
Platelets 50,000/L (50 109/L)
Total bilirubin 3 mg/dL (except Gilbert syndrome, in which direct bilirubin should be 5 mg/dL)
Alanine aminotransferase 3 upper limit of normal (ULN), aspartate aminotransferase 3 ULN

Exclusion Criteria

Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement)
Increased calcium levels: Corrected serum calcium >1 mg/dL above the ULN or >11 mg/dL
Renal insufficiency: Determined by glomerular filtration rate (GFR) <40 mL/min/1.73 m (Modification of Diet in Renal Disease [MDRD] Formula) or serum creatinine >2 mg/dL
Anemia (hemoglobin 2 g/dL below lower limit of normal or <10 g/dL or both) transfusion support or concurrent treatment with erythropoietin stimulating agents is not permitted
BMPCs 60%
Serum involved/uninvolved FLC ratio 100
Whole body magnetic resonance imaging (WB-MRI) or positron emission tomography-computed tomography (PET-CT) with more than 1 focal lesion (5 mm in diameter by MRI)
Uncontrolled infection within 28 days prior to randomization in Phase 3 or first study intervention administration in safety run-in
bone lytic lesion of 5mm in size
Clinically significant cardiac disease, including
Myocardial infarction within 6 months with left ventricular dysfunction or uncontrolled ischemic cardiac disease before Cycle 1 Day 1, or 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 (Grade 2 or higher by NCI-CTCAE Version 5.0) or clinically significant electrocardiogram (ECG) abnormalities
Known acquired immunodeficiency syndrome (AIDS)-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment or active hepatitis A (defined as positive hepatitis A antigen or positive IgM). HIV serology at screening will be tested for German participants and any other country where required as per local regulations and serology hepatitis B and C at screening will be tested for all participants
Primary systemic and localized amyloid light-chain (immunoglobulin light chain) amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), standard risk smoldering myeloma, soft tissue plasmacytoma, symptomatic myeloma
Uncontrolled or active HBV infection: Patients with positive HBsAg and/or HBV DNA
Of note
Patient can be eligible if anti-HBc IgG positive (with or without positive
anti-HBs) but HBsAg and HBV DNA are negative. If anti-HBV therapy in relation
with prior infection was started before initiation of IMP, the anti-HBV
Patients with negative HBsAg and positive HBV DNA observed during screening
period will be evaluated by a specialist for start of anti-viral treatment
study treatment could be proposed if HBV DNA becomes negative and all the
other study criteria are still met
therapy and monitoring should continue throughout the study-treatment period
Active HCV infection: positive HCV RNA and negative anti-HCV
Of note
Patients with antiviral therapy for HCV started before initiation of IMP and
positive HCV antibodies are eligible. The antiviral therapy for HCV should
continue throughout the treatment period until seroconversion
Patients with positive anti-HCV and undetectable HCV RNA without antiviral
therapy for HCV are eligible
Malabsorption syndrome or any condition that can significantly impact the absorption of lenalidomide
Any of the following within 3 months prior to randomization (or first study intervention administration in safety run-in cohort): treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event
Received treatment (eg surgery, radiotherapy, medication) for a malignancy within 3 years of randomization (or first study intervention administration in safety run-in cohort)
Prior exposure to approved or investigational treatments for SMM or MM (including but not limited to conventional chemotherapies, immunomodulatory imid drugs, or Proteasome inhibitors); concurrent use of bisphosphonates or receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor denosumab is not permitted; however, prior bisphosphonates or once-a-year intravenous bisphosphonate given for the treatment of osteoporosis is permitted
Ongoing treatment with corticosteroids with a dose >10 mg prednisone or equivalent per day at the time of randomization (or first study intervention administration in safety run-in cohort)
Women of childbearing potential or male participant with women of childbearing potential who do not agree to use a highly effective method of birth control
Vaccination with a live vaccine 4 weeks before the start of the study drug. Seasonal flu vaccines that do not contain live virus are permitted
The above information is not intended to contain all considerations relevant
to a patient's potential participation in a clinical trial
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note