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Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients (ICARIA-MM)

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ClinicalTrials.gov Identifier: NCT02990338
Recruitment Status : Active, not recruiting
First Posted : December 13, 2016
Last Update Posted : June 28, 2018
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

To demonstrate the benefit of isatuximab in combination with pomalidomide and low-dose dexamethasone in the prolongation of Progression Free Survival (PFS) as compared to pomalidomide and low-dose dexamethasone in patients with refractory or relapsed and refractory multiple myeloma (MM).

Secondary Objectives:

  • To evaluate the Overall Response Rate (ORR) as per International Myeloma Working Group (IMWG) criteria in each arm.
  • To compare the Overall Survival (OS) between the two arms.
  • To evaluate the Time To Progression (TTP) in each arm.
  • To evaluate the Progression Free Survival (PFS) in high risk cytogenetic population in each arm.
  • To evaluate the Duration of Response (DOR) in each arm.
  • To evaluate the safety in both treatment arms.
  • To determine the Pharmacokinetic profile of isatuximab in combination with pomalidomide.
  • To evaluate the immunogenicity of isatuximab.
  • To assess disease-specific and generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility, and health status.

Condition or disease Intervention/treatment Phase
Plasma Cell Myeloma Drug: isatuximab SAR650984 Drug: pomalidomide Drug: dexamethasone Phase 3

Detailed Description:

The duration of the study for the patients will include a period for screening of up to 21 days (or up to 28 days for women who can become pregnant). Patients will continue study treatment until disease progression, unacceptable adverse reaction, patients' wish or other reason of discontinuation.

During follow-up, patients who discontinue the study treatment due to progression of the disease will be followed every 3 months (12 weeks) for survival (or until cut- off date), and patients who discontinue the study treatment prior to documentation of disease progression will be followed-up every 4 weeks until disease progression, and then every 3 months (12 weeks) for survival (or until cut-off date).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Study Start Date : December 22, 2016
Estimated Primary Completion Date : November 23, 2020
Estimated Study Completion Date : November 23, 2020


Arm Intervention/treatment
Experimental: IPd (Isatuximab + Pomalidomide + Dexamethasone)
Isatuximab (intravenous) on Day 1, 8, 15, and 22 of 1st 28-day cycle, then on Day 1 and 15 of subsequent cycles in combination with pomalidomide per os on Day 1 to 21 + dexamethasone IV (intravenous) or per os on Day 1, 8, 15, 22 in 28-day cycles up to disease progression
Drug: isatuximab SAR650984
Pharmaceutical form:solution for infusion Route of administration: intravenous

Drug: pomalidomide
Pharmaceutical form:capsule Route of administration: oral
Other Name: POMALYST IMNOVID

Drug: dexamethasone
Pharmaceutical form:tablets or solution for infusion Route of administration: oral or intravenous

Active Comparator: Pd (Pomalidomide + Dexamethasone)
Pomalidomide per os on Day 1 to 21 + dexamethasone IV (intravenous) or per os on Day 1, 8, 15, 22 in 28-day cycles up to disease progression
Drug: pomalidomide
Pharmaceutical form:capsule Route of administration: oral
Other Name: POMALYST IMNOVID

Drug: dexamethasone
Pharmaceutical form:tablets or solution for infusion Route of administration: oral or intravenous




Primary Outcome Measures :
  1. 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, whichever comes first, assessed approximatively up to 18 months ]

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: From the date of randomization to the date of first documentation of progression, assessed approximately up to 18 months ]
  2. Overall Survival (OS) [ Time Frame: up to 51 months ]
  3. Time to Progression (TTP) [ Time Frame: From the date of randomization to the date of first documentation of progression, assessed approximately up to 18 months ]
  4. 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, whichever comes first, assessed approximately up to 18 months ]
  5. Duration of response [ Time Frame: From the date of randomization to the date of first documentation of progression or the date of death from any cause, whichever comes first, assessed approximately up to 18 months ]
  6. Number of patients with adverse events according to the National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 4.03 grade scaling [ Time Frame: Up to 30 days after last study treatment administration ]
  7. Patient-reported outcome measured with Quality of Life questionnaire EORTC-QLQ-C30 [ Time Frame: Approximately up to 18 months ]
  8. Patient-reported outcome measured with Quality of Life questionnaire MY20 [ Time Frame: Approximately up to 18 months ]
  9. Patient-reported outcome measured with Quality of Life questionnaire EQ-5D-5L [ Time Frame: Approximately up to 18 months ]
  10. Plasma concentrations of isatuximab (IPd Arm) [ Time Frame: Up to 30 days after last study treatment administration ]
  11. Immune response (IPd Arm) : levels of human anti-drug antibodies (ADA) [ Time Frame: Up to 60 days after last study treatment administration, or until test is negative whichever comes last ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Age superior or equal to 18 years or country's legal age of majority if the legal age is superior to 18 years old.
  • Patients must have a documented diagnosis of multiple myeloma with evidence of measurable disease i.e. serum M protein superior or equal to 0.5 g per 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.
  • Patients must have 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.
  • Patients must have failed treatment with lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) alone or in combination.
  • Patients must have 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 patients who have 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 µL if inferior to 50% of bone marrow (BM) nucleated cells are plasma cells, and inferior to 30 000 cells per µL if superior or equal to 50% of BM nucleated cells are plasma cells. Platelet transfusion is not allowed within three days before the screening visit.
  • Absolute neutrophils count inferior to 1000 per μL (1 x 10E9/L). The use of G-CSF is not allowed to reach this level.
  • Creatinine clearance inferior to 30 mL per min (MDRD Formula).
  • Total bilirubin superior to 2 x ULN (Upper Limit of Normal).
  • Corrected serum calcium superior to 14 mg per dL (superior to 3.5 mmol per L).
  • Aspartate aminotransferase (AST) and/or Alanine Aminotransferase (ALT) superior to 3 x ULN.
  • Hypersensitivity to 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 disagree to practice true abstinence or disagree 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 months following study treatment discontinuation, even if he has undergone a successful vasectomy.
  • All patients who disagree to refrain from donating blood while on study treatment and for 4 weeks after discontinuation from this study treatment.

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02990338


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Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02990338     History of Changes
Other Study ID Numbers: EFC14335
2016‐003097‐41 ( EudraCT Number )
U1111-1180-6262 ( Other Identifier: UTN )
First Posted: December 13, 2016    Key Record Dates
Last Update Posted: June 28, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available Sanofi continues to protect the privacy of the participants in clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Pomalidomide
Thalidomide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents