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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 6, 2019
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).


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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
Actual Primary Completion Date : November 22, 2018
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.


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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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Locations
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United States, Florida
Investigational Site Number 8400002
Plantation, Florida, United States, 33324
United States, Massachusetts
Investigational Site Number 8400006
Boston, Massachusetts, United States, 02215
Australia
Investigational Site Number 0360005
Melbourne, Australia, 3000
Investigational Site Number 0360002
Prahran, Australia, 3004
Investigational Site Number 0360006
Richmond, Australia, 3121
Investigational Site Number 0360004
St Leonards, Australia, 2065
Investigational Site Number 0360001
Waratah, Australia, 2298
Belgium
Investigational Site Number 0560003
Antwerpen, Belgium, 2060
Investigational Site Number 0560002
Brussel, Belgium, 1090
Investigational Site Number 0560004
Gent, Belgium, 9000
Investigational Site Number 0560001
Leuven, Belgium, 3000
Canada
Investigational Site Number 1240001
Montreal, Canada, H1T 2M4
Investigational Site Number 1240004
Montreal, Canada, H4A 3J1
Investigational Site Number 1240005
Sherbrooke, Canada, J1H 5N4
Czechia
Investigational Site Number 2030005
Brno, Czechia, 62500
Investigational Site Number 2030004
Hradec Kralove, Czechia, 50005
Investigational Site Number 2030001
Olomouc, Czechia, 77900
Investigational Site Number 2030002
Ostrava - Poruba, Czechia, 70852
Investigational Site Number 2030003
Praha 2, Czechia, 12808
Denmark
Investigational Site Number 2080002
Ålborg, Denmark, 9100
France
Investigational Site Number 2500021
Bayonne, France, 64100
Investigational Site Number 2500008
Caen, France, 14033
Investigational Site Number 2500009
Dijon, France, 21000
Investigational Site Number 2500017
Grenoble, France, 38043
Investigational Site Number 2500013
La Roche Sur Yon, France, 85925
Investigational Site Number 2500003
Lille, France, 59037
Investigational Site Number 2500023
Limoges, France, 87042
Investigational Site Number 2500019
Montpellier Cedex, France, 34295
Investigational Site Number 2500002
Nantes Cedex 01, France, 44093
Investigational Site Number 2500015
Paris, France, 75005
Investigational Site Number 2500016
Paris, France, 75743
Investigational Site Number 2500005
Pessac, France, 33600
Investigational Site Number 2500004
Pierre Benite, France, 69495
Investigational Site Number 2500007
Poitiers, France, 86000
Investigational Site Number 2500025
Reims, France, 51092
Investigational Site Number 2500014
Rennes, France, 35033
Investigational Site Number 2500001
Toulouse Cedex 9, France, 31059
Investigational Site Number 2500012
Tours, France, 37044
Investigational Site Number 2500018
Vandoeuvre-Les-Nancy, France, 54500
Germany
Investigational Site Number 2760001
Leipzig, Germany, 04103
Greece
Investigational Site Number 3000002
Athens, Greece, 106 76
Investigational Site Number 3000005
Athens, Greece, 11527
Investigational Site Number 3000001
Athens, Greece, 11528
Investigational Site Number 3000004
Patra, Greece, 26504
Investigational Site Number 3000003
Thessaloniki, Greece, 57010
Hungary
Investigational Site Number 3480001
Budapest, Hungary, 1083
Investigational Site Number 3480003
Budapest, Hungary, 1097
Investigational Site Number 3480002
Debrecen, Hungary, 4032
Italy
Investigational Site Number 3800001
Bologna, Italy, 40138
Investigational Site Number 3800010
Catania, Italy, 95123
Investigational Site Number 3800009
Firenze, Italy, 50134
Investigational Site Number 3800008
Genova, Italy, 16132
Investigational Site Number 3800007
Milano, Italy, 20132
Investigational Site Number 3800002
Milano, Italy, 20133
Investigational Site Number 3800006
Padova, Italy, 35128
Investigational Site Number 3800004
Terni, Italy, 05100
Investigational Site Number 3800003
Torino, Italy, 10126
Japan
Investigational Site Number 3920006
Kyoto-Shi, Japan
Investigational Site Number 3920001
Nagoya-Shi, Japan
Investigational Site Number 3920003
Okayama-Shi, Japan
Investigational Site Number 3920004
Sapporo-Shi, Japan
Investigational Site Number 3920005
Shibukawa-Shi, Japan
Investigational Site Number 3920002
Shibuya-Ku, Japan
Investigational Site Number 3920007
Sunto-Gun, Japan
Investigational Site Number 3920008
Suwa-Shi, Japan
Korea, Republic of
Investigational Site Number 4100007
Hwasun-Gun, Korea, Republic of, 58128
Investigational Site Number 4100006
Incheon, Korea, Republic of, 21565
Investigational Site Number 4100001
Seoul, Korea, Republic of, 03080
Investigational Site Number 4100002
Seoul, Korea, Republic of, 06351
Investigational Site Number 4100005
Seoul, Korea, Republic of, 06591
New Zealand
Investigational Site Number 5540002
Auckland, New Zealand, 2025
Investigational Site Number 5540004
Dunedin, New Zealand, 9016
Investigational Site Number 5540003
Hamilton, New Zealand, 3204
Investigational Site Number 5540001
Takapuna, New Zealand, 1309
Norway
Investigational Site Number 5780001
Oslo, Norway, 0342
Poland
Investigational Site Number 6160002
Chorzow, Poland, 41-500
Investigational Site Number 6160005
Krakow, Poland, 31-501
Investigational Site Number 6160003
Lublin, Poland, 20-081
Investigational Site Number 6160001
Warszawa, Poland, 02-776
Portugal
Investigational Site Number 6200004
Coimbra, Portugal, 3000-075
Investigational Site Number 6200002
Lisboa, Portugal, 1070
Investigational Site Number 6200001
Porto, Portugal, 4200
Russian Federation
Investigational Site Number 6430004
Moscow, Russian Federation, 125167
Investigational Site Number 6430001
Moscow, Russian Federation, 125284
Investigational Site Number 6430002
Moscow, Russian Federation, 129301
Slovakia
Investigational Site Number 7030001
Bratislava, Slovakia, 83310
Spain
Investigational Site Number 7240001
Barcelona, Spain, 08035
Investigational Site Number 7240003
Madrid, Spain, 28006
Investigational Site Number 7240002
Pamplona, Spain, 31008
Investigational Site Number 7240004
Salamanca, Spain, 37007
Investigational Site Number 7240006
Santander, Spain, 39008
Investigational Site Number 7240005
Santiago De Compostela, Spain, 15706
Sweden
Investigational Site Number 7520004
Luleå, Sweden, 97180
Investigational Site Number 7520005
Uddevalla, Sweden, 451 80
Taiwan
Investigational Site Number 1580004
Kaohsiung, Taiwan, 833
Investigational Site Number 1580002
Taichung, Taiwan, 40447
Investigational Site Number 1580001
Taipei, Taiwan, 100
Investigational Site Number 1580003
Taoyuan, Taiwan, 333
Turkey
Investigational Site Number 7920001
Ankara, Turkey
Investigational Site Number 7920002
Antalya, Turkey
Investigational Site Number 7920005
Istanbul, Turkey, 34010
Investigational Site Number 7920003
Istanbul, Turkey, 34390
Investigational Site Number 7920004
Istanbul, Turkey
Investigational Site Number 7920006
İstanbul, Turkey
Investigational Site Number 7920008
Izmir, Turkey, 35040
Investigational Site Number 7920010
Izmir, Turkey, 35340
Investigational Site Number 7920009
Kayseri, Turkey, 38039
Investigational Site Number 7920007
Kocaeli, Turkey, 41400
United Kingdom
Investigational Site Number 8260002
London, United Kingdom, EC1A 7BE
Investigational Site Number 8260003
London, United Kingdom, SE1 9RT
Investigational Site Number 8260001
London, United Kingdom, WC1E 6BT
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

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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 6, 2019
Last Verified: June 2019
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:
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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
Thalidomide
Dexamethasone
Dexamethasone acetate
Pomalidomide
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