SC Versus IV Isatuximab in Combination With Pomalidomide and Dexamethasone in RRMM (IRAKLIA)

Sanofi

Status and phase: Active, not recruiting; Phase 3

Conditions: Plasma Cell Myeloma Recurrent

Treatments: Drug: Montelukast; Drug: Dexamethasone; Drug: Methylprednisolone; Drug: Isatuximab IV; Drug: Isatuximab SC; Drug: Diphenhydramine; Drug: Paracetamol / Acetaminophen; Drug: Pomalidomide

Study type: Interventional

Funder types: Industry

Identifiers

NCT05405166

2021-002485-41 (EudraCT Number)

2023-508869-32 (Registry Identifier)

U1111-1261-5846 (Registry Identifier)

EFC15951

Details and patient eligibility

About

This is a randomized, multicenter, Phase 3, open-label study evaluating subcutaneous (SC) vs intravenous (IV) administration of isatuximab in combination with pomalidomide and dexamethasone (Pd) in RRMM patients (study participants) who have received at least 1 prior line of therapy including lenalidomide and a proteasome inhibitor (PI). Eligible participants will be randomized 1:1 into 1 of 2 study arms:

Arm SC: Isatuximab SC + Pd

Arm IV: Isatuximab IV + Pd

Participants will be allowed to continue therapy until disease progression, unacceptable adverse events (AEs), participant request to discontinue therapy or any other reason, whichever comes first.

Full description

Two study arms will be treated in 4-week cycles until disease progression, unacceptable adverse events (AEs), participant request to discontinue therapy or any other reason, whichever comes first.

Enrollment: 531 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants with multiple myeloma who have received at least one prior line of anti-myeloma therapy, which must include lenalidomide and a proteasome inhibitor given alone or in combination.
• Measurable serum M-protein (≥ 0.5 g/dL) and/or urine M-protein (≥ 200 mg/24 hours) and/or serum free light chain (FLC) assay (Involved FLC assay ≥10 mg/dL and abnormal serum FLC ratio (<0.26 or >1.65)).

Exclusion criteria

• Primary refractory multiple myeloma participants
• Participants with prior anti-CD38 treatment: (a) administered less than 9 months before randomization or, (b) intolerant to the anti-CD38 previously received
• Prior therapy with pomalidomide
• Participants with inadequate biological tests.
• Significant cardiac dysfunction
• Participants diagnosed or treated for another malignancy within 3 years prior to randomization with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, and in situ malignancy, or low risk prostate cancer after curative therapy
• Concomitant plasma cell leukemia
• Active primary amyloid light -chain amyloidosis
• Known acquired immunodeficiency syndrome (AIDS)-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment
• Know active Hepatitis A infection. Current active or chronic hepatitis B (HBV) or hepatitis C (HCV) infection. Participants with chronic HBV or HCV disease that is controlled under antiviral therapy are allowed.
• Women of childbearing potential or male participant with women of childbearing potential who do not agree to use highly effective method of birth control

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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531 participants in 2 patient groups

Isatuximab Subcutaneous (SC)

Experimental group

Description:

Isatuximab dose will be administered SC weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days in duration. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication.

Treatment:

Drug: Pomalidomide

Drug: Paracetamol / Acetaminophen

Drug: Diphenhydramine

Drug: Dexamethasone

Drug: Isatuximab SC

Drug: Methylprednisolone

Drug: Montelukast

Drug: Dexamethasone

Isatuximab Intravenous (IV)

Active Comparator group

Description:

Isatuximab dose will be administered via IV infusion weekly for 4 weeks during Cycle 1 (Days 1, 8, 15, and 22) and Day 1 and 15 of subsequent cycles. Each cycle will be 28 days. Pomalidomide dose will be taken orally on Day 1 to Day 21 of each cycle at the time that is the most convenient for the participants prior to or after isatuximab administration, preferably at the same time every day. Dexamethasone will be taken orally on Day 1, 8, 15 and 22 (to be repeated every 28 days). Participants may receive other treatments as background treatment and/or rescue medication.

Treatment:

Drug: Pomalidomide

Drug: Paracetamol / Acetaminophen

Drug: Diphenhydramine

Drug: Dexamethasone

Drug: Methylprednisolone

Drug: Isatuximab IV

Drug: Montelukast

Drug: Dexamethasone