Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 27 November 2023
• Main ID: NCT02990338
• Date of registration: 04/12/2016
• Prospective Registration: Yes
• Primary sponsor: Sanofi
• Public title: Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients ICARIA-MM
• Scientific title: A Phase 3 Randomized, Open-label, Multicenter Study Comparing Isatuximab (SAR650984) in Combination With Pomalidomide and Low-Dose Dexamethasone Versus Pomalidomide and Low-Dose Dexamethasone in Patients With Refractory or Relapsed and Refractory Multiple Myeloma
• Date of first enrolment: December 22, 2016
• Target sample size: 307
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02990338
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Australia, Belgium, Canada, Czechia, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, New Zealand, Norway, Poland, Portugal, Russian Federation, Slovakia, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Sciences & Operations
• Affiliation: Sanofi

Key inclusion & exclusion criteria

Inclusion criteria :

- Age superior or equal to 18 years or country's legal age of majority if the legal age
was superior to 18 years old.

- Participants had a documented diagnosis of multiple myeloma with evidence of
measurable disease i.e. serum M protein superior or equal to 0.5 grams per decilitre
(g/dL) measured using serum protein immunoelectrophoresis and or urine M protein
superior or equal to 200 mg per 24 hours measured using urine protein
immunoelectrophoresis.

- Participants had received at least 2 prior lines of anti-myeloma therapy, which must
include at least 2 consecutive cycles of lenalidomide and a proteasome inhibitor
(bortezomib, carfilzomib or ixazomib) given alone or in combination.

- Participants had failed treatment with lenalidomide and a proteasome inhibitor
(bortezomib, carfilzomib, or ixazomib) alone or in combination (Intolerant,
progression within 6 months after reaching Partial Response or better).

- Participants had progressed on or within 60 days after end of previous therapy before
to study entry, i.e., refractory to the last line of treatment.

Exclusion criteria:

- Primary refractory multiple myeloma defined as participants who had never achieved at
least a minimal response (MR) with any treatment during the disease course.

- Free Light Chain measurable disease only.

- Prior therapy with pomalidomide.

- Any anti-myeloma drug treatment within 14 days before randomization, including
dexamethasone.

- Eastern Cooperative Oncology Group performance status superior to 2.

- Platelets inferior to 75 000 cells per microliter (mcL) if inferior to 50% of bone
marrow (BM) nucleated cells are plasma cells, and inferior to 30 000 cells per mcL if
superior or equal to 50% of BM nucleated cells are plasma cells. Platelet transfusion
was not allowed within three days before the screening visit.

- Absolute neutrophil count inferior to 1000 per mcL (1*10^9/L).

- Creatinine clearance inferior to 30 mL per minute (Modification of Diet in Renal
Disease [MDRD] Formula).

- Total bilirubin superior to 2*ULN (Upper Limit of Normal).

- Corrected serum calcium superior to 14 milligrams per deciliter (mg/dL) (superior to
3.5 millimoles per liter (mmol/L).

- Aspartate aminotransferase (AST) and/or Alanine Aminotransferase (ALT) superior to
3*ULN.

- Hypersensitivity to immunomodulatory drugs (IMiDs) (thalidomide or lenalidomide)
defined as any hypersensitivity reaction leading to stop IMiDs within the 2 first
cycles or toxicity, which does meet intolerance definition.

- Hypersensitivity to dexamethasone, sucrose histidine (as base and hydrochloride salt),
and polysorbate 80 or any of the components of study therapy that are not amenable to
premedication with steroids, or H2 blockers that would prohibit further treatment with
these agents.

- Significant cardiac dysfunction; myocardial infarction within 12 months; unstable,
poorly controlled angina pectoris.

- Pregnant or breastfeeding woman or female who intends to become pregnant during the
participation in the study.

- Male participants who disagreed to practice true abstinence or disagreed to use a
condom during sexual contact with a pregnant female or a female of childbearing
potential while participating in the study, during dose interruptions and at least 3
or 5 months following study treatment discontinuation, even if he had undergone a
successful vasectomy.

- All participants who disagreed to refrain from donating blood while on study treatment
and for 4 weeks after discontinuation from this study treatment.

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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Plasma Cell Myeloma

Intervention(s)

Drug: Dexamethasone

Drug: Isatuximab

Drug: Pomalidomide

Primary Outcome(s)

Progression Free Survival (PFS) [Time Frame: From the date of randomization to the date of first documentation of progression, or the date of death from any cause, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration: 76.7 weeks)]

Secondary Outcome(s)

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Disease Symptoms Domain Score [Time Frame: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)]

Progression Free Survival in High Risk Cytogenetic Population [Time Frame: From the date of randomization to the date of first documentation of progression, or the date of death from any cause, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)]

Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health State Utility Index Value [Time Frame: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)]

Overall Response Rate (ORR): Percentage of Participants With Disease Response as Per Independent Response Committee (IRC) [Time Frame: From the date of randomization to the date of first documentation of progression or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)]

Clinical Benefit Rate (CBR): Percentage of Participants With Clinical Benefit as Per Independent Response Committee [Time Frame: From the date of randomization to the date of first documentation of progression, death, initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)]

Number of Participants With Anti-drug Antibodies (ADA) [Time Frame: From randomization up to 60 days after last dose of study drug (maximum duration 76.7 weeks)]

Time to Best Response (TTBR) as Per Independent Response Committee [Time Frame: From the date of randomization to date of first occurrence of IRC determined best overall response or data cut-off whichever comes first (maximum duration 76.7 weeks)]

Percentage of Participants With Best Overall Response (BOR) as Per Independent Response Committee [Time Frame: From the date of randomization until disease progression, or death, initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)]

Time to Progression (TTP) as Per Independent Response Committee [Time Frame: From the date of randomization to the date of first documentation of progression, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)]

Pharmacokinetic Parameter: Accumulation Ratio of Isatuximab at Concentration at the End of Infusion (CEOI) [Time Frame: End of infusion on Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 4 Day 1]

Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS) [Time Frame: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)]

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 30 Items (EORTC QLQ-C30): Global Health Status (GHS)/Quality of Life (QOL) Score [Time Frame: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)]

Pharmacokinetics (PK) Parameter: Plasma Concentration of Isatuximab at End of Infusion (CEOI) [Time Frame: End of infusion on Cycle(C)1 Day(D)1 and Cycle1 Day 15; Cycle 2 Day 1; and Cycle 4 Day 1]

PK Parameter: Accumulation Ratio of Isatuximab at Trough Concentration (Ctrough) [Time Frame: Pre-infusion on Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 4 Day 1]

Time to First Response (TT1R) as Per Independent Response Committee [Time Frame: From the date of randomization to the date of first IRC determined response, or death or data cut-off whichever comes first (maximum duration 76.7 weeks)]

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Time Frame: From randomization up to 30 days after last dose of study drug (maximum duration up to 241.6 weeks for Pd arm and 245.6 weeks for IPd arm)]

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Side Effects of Treatment Domain Score [Time Frame: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)]

Duration of Response (DOR) as Per Independent Response Committee [Time Frame: From the date of the first IRC determined response to the date of first IRC progression or death, whichever occurred first (maximum duration 76.7 weeks)]

Overall Survival (OS): Final Analysis [Time Frame: From the date of randomization to date of death from any cause or data cut-off date, whichever was earlier (maximum duration 245.6 weeks)]

Number of Participants With Minimal Residual Disease (MRD) [Time Frame: Up to 76.7 weeks]

Percentage of Participants With Very Good Partial Response (VGPR) or Better as Per Independent Response Committee [Time Frame: From the date of randomization to the date of first documentation of progression, death, initiation of further anti-myeloma treatment, or data cut-off whichever comes first (maximum duration 76.7 weeks)]

Pharmacokinetic Parameter: Plasma Concentration of Isatuximab at 1 Hour After End of Infusion (CEOI+1 Hour) [Time Frame: Cycle 1:1 hour after End of Infusion on Day 1; Cycle 4:1 hour after End of Infusion on Day 1]

PK Parameter: Plasma Concentration of Isatuximab at Ctrough [Time Frame: Pre-infusion on C1D1, C1D8, C1D15, C1D22, C2D1, C2D15, C3D1, C3D15, C4D1, C4D15, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1; End of treatment (EOT [30 days after last drug administration])]

Secondary ID(s)

U1111-1180-6262

2016-003097-41

EFC14335

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 06/12/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02990338