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Trial record 1 of 1 for:    ICARIA-MM | Multiple Myeloma
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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02990338
Recruitment Status : Active, not recruiting
First Posted : December 13, 2016
Results First Posted : December 6, 2019
Last Update Posted : August 12, 2020
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 participants 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 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 Drug: Pomalidomide Drug: Dexamethasone Phase 3

Detailed Description:

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

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 307 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
Actual Study Start Date : December 22, 2016
Actual Primary Completion Date : November 22, 2018
Estimated Study Completion Date : March 2022


Arm Intervention/treatment
Active Comparator: Pd (pomalidomide + dexamethasone)
Participants received pomalidomide 4 milligrams (mg) Per os (PO) on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants greater than or equal to (>=) 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).
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

Experimental: IPd (isatuximab + pomalidomide + dexamethasone)
Participants received isatuximab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Drug: Isatuximab
Pharmaceutical form:solution for infusion Route of administration: intravenous
Other Names:
  • SAR650984
  • Sarclisa

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, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration: 76.7 weeks) ]
    PFS:time from date of randomization to date of first documentation of progressive disease (PD) determined by Independent Response Committee (IRC) or date of death from any cause, whichever comes first. If progression or death was not observed, participant was censored at date of last progression-free tumor assessment prior to study cut-off date. Analysis was performed by Kaplan-Meier method. PD as per International Myeloma Working Group (IMWG) criteria was defined as increase of >=25% from lowest confirmed value in any one of the following criteria: serum M-protein (the absolute increase must be >=0.5gram(g)/dL), serum M-protein increase >=1g/dL if lowest M component was >=5g/dL; urine M-component (absolute increase must be >=200mg/24hour), appearance of new lesion(s),>=50% increase from nadir in sum of the products of the maximal perpendicular diameters of measured lesions (SPD) of >1 lesion, or >=50% increase in the longest diameter of a previous lesion >1 centimeter in short axis.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR): Percentage of Participants With Overall Response [ 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) ]
    ORR:percentage of participants with stringent complete response(sCR), complete response(CR), very good partial response(VGPR), and partial response(PR) as best overall response, assessed by IRC using IMWG criteria. sCR:negative immunofixation on serum and urine,disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates plus normal free light chain(FLC)ratio(0.26-1.65), absence of clonal cells in bone marrow biopsy.CR:negative immunofixation on serum and urine,disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates.VGPR: serum and urine M-protein detectable by immunofixation, not on electrophoresis/,>=90% reduction in serum M-protein plus urine M-protein level <100mg/24h/,>=90% decrease in SPD compared to baseline in soft tissue plasmacytoma. PR: >=50% reduction of serum M-protein and reduction in 24h urinary M-protein by >=90%/<200mg/24h,if present at baseline,>=50% reduction in the size(SPD) of soft tissue plasmacytomas.

  2. Overall Survival (OS) [ Time Frame: From the date of randomization to date of death from any cause or study cut-off date, whichever was earlier (maximum duration 76.7 weeks) ]
    OS was defined as the time from the date of randomization to death from any cause. In the absence of confirmation of death, survival time was censored at the last date participant was known to be alive or at the cut-off date, whichever comes first.

  3. Time to Progression (TTP) [ 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) ]
    TTP was defined as time from randomization to the date of first documentation of PD, as determined by the IRC. As per IMWG criteria, PD was defined for participants with increase of >= 25% from lowest confirmed value in any one of the following criteria: serum M-protein (the absolute increase must be >= 0.5 g/dL), serum M-protein increase >=1 g/dL if the lowest M component was >=5 g/dL; urine M-component (the absolute increase must be >=200 mg/24hour), appearance of new lesion(s), >=50% increase from nadir in SPD of >1 lesion, or >=50% increase in the longest diameter of a previous lesion >1 centimeter in short axis.

  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, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks) ]
    PFS in high risk cytogenetic population was defined as PFS in subgroup of participants carrying high risk cytogenetic changes including del(17p), translocation (t)(4;14) or translocation t(14;16) assessed by fluorescence in situ hybridization (FISH). PFS was defined as the time from date of randomization to date of first documentation of PD (determined by IRC) or date of death from any cause, whichever comes first. PD defined as per IMWG criteria as: increase of >=25% from lowest confirmed value in any one of following criteria: serum M-protein (absolute increase must be >=0.5 g/dL), serum M-protein increase >=1 g/dL if lowest M component was >=5 g/dL; urine M-component (absolute increase must be >=200 mg/24hour), appearance of new lesion(s), >=50% increase from nadir in SPD of >1 lesion, or >=50% increase in the longest diameter of previous lesion >1 centimeter (cm) in short axis.

  5. Duration of Response (DOR) [ 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) ]
    DOR:time from date of first IRC determined response(PR or better) to date of first IRC-PD or death, whichever occurred first.DOR was determined only for participants who had achieved a response of PR or better based on disease assessment by IRC.If progression or death was not observed,participant was censored at date of participants last progression-free tumor assessment prior to initiation of further anti-myeloma treatment(if any)and study cut-off date. PD(IMWG criteria):increase of >=25% from lowest confirmed value in any one of following criteria: serum M-protein (absolute increase must be >=0.5 g/dL), serum M-protein increase >=1g/dL if lowest M component was >=5g/dL;urine M-component (absolute increase must be >=200mg/24 hour),appearance of new lesion(s), >=50% increase from nadir in SPD of >1 lesion,or >=50% increase in the longest diameter of a previous lesion >1 cm in short axis. PR:>=50% reduction of serum M-protein and reduction in 24h urinary M-protein by >=90%/<200mg/24h.

  6. 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 76.7 weeks) ]
    Adverse Event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed, worsened (according to the Investigator opinion), or became serious during the treatment period (time from the first dose of study treatments up to 30 days after last dose of study treatments). An SAE is any untoward medical occurrence that at any dose: results in death, Is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect, is a medically important event.

  7. 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 ]
    CEOI was defined as the plasma concentration at end of infusion.

  8. 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 ]
    Accumulation Ratio was defined as the ratio of CEOI of Cycle 2 Day 1 versus Cycle 1 Day 1 and Cycle 4 Day 1 versus Cycle 1 Day 1, where CEOI was the plasma concentration at the end of infusion.

  9. 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 ]
    CEOI+1 hour was defined as the plasma concentration of isatuximab at 1 hour after end of infusion.

  10. 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]) ]
    Trough Concentration (Ctrough) is the concentration prior to study drug administration.

  11. 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 ]
    Accumulation Ratio was defined as the ratio of Ctrough of Cycle 2 Day 1 versus Cycle 1 Day 8 and Cycle 4 Day 1 versus Cycle 1 Day 8, where Ctrough is the concentration prior to study drug administration.

  12. 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) ]
    ADA were categorized as: pre-existing, treatment induced and treatment boosted response. Pre-existing ADA was defined as ADA that were present in samples drawn during the pretreatment period (i.e., before the first isatuximab administration). Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period in participants without preexisting ADA, including participants without pretreatment samples. Treatment boosted ADA was defined as pre-existing ADA that increased at least 2 titer steps between pre-treatment and post-treatment.

  13. 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) ]
    EORTC-Quality of Life Questionnaire (QLQ)-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. EORTC QLQ-C30 included GHS/ QOL, functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 were a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were a 7-point scale (1/Very Poor to 7/Excellent). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant.

  14. 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) ]
    EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. Disease symptoms domain is one of the four domain scores. Disease symptoms domain score used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0 -100 scale, where higher scores = more symptoms and lower health-related quality of life (HRQL) and lower score = less symptoms and more HRQL

  15. 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) ]
    EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. Side effects of treatment domain is one of the four domain scores. Side effects of treatment domain score used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale, where higher scores = more side effects and lower HRQL and lower scores = less side effects and better HRQL.

  16. 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) ]
    The EQ-5D-5L is a standardized measure of health status that provides a general assessment of health and wellbeing. The EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has a 5-level response: no problems, slight problems, moderate problems, severe problems, and extreme problems. Response options are measured with a 5-point Likert scale (for the 5L version). The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state and lower score indicate worse health state.

  17. 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) ]
    EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state utility index (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.

  18. Percentage of Participants With Best Overall Response (BOR) [ 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) ]
    BOR:best sequential response from start of treatment until disease progression,death, initiation of further anti-myeloma treatment/data cut-off, whichever comes first. Ordering of evaluations from best to worse was: sCR,CR,VGPR,PR, minimal response(MR), stable disease(SD),PD, and not evaluable.CR:negative immunofixation on serum and urine,disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates. sCR:CR as defined previously plus normal FLC ratio (0.26 to 1.65),absence of clonal cells in bone marrow biopsy. VGPR: serum and urine M-protein detectable by immunofixation,>=90% reduction in serum M-protein plus urine M-protein level <100mg/24h,>=90% decrease in SPD compared to baseline in soft tissue plasmacytoma. PR: >=50% reduction of serum M-protein and reduction in 24h urinary M-protein by >=90%/<200mg/24h. MR:>=25% but <=49% reduction in serum M-protein and reduction in 24h urine M-protein by 50-89%. SD: Not meeting criteria for CR,VGPR,PR,MR/PD.

  19. Clinical Benefit Rate (CBR): Percentage of Participants With Clinical Benefit [ 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) ]
    CBR was defined as the percentage of participants achieving a MR or better as BOR. MR was defined as >= 25% but <= 49% reduction in serum M-protein and reduction in 24h urine M-protein by 50-89%, which still exceed 200 mg/24h; if present at baseline, >=50% reduction in size (SPD) of soft tissue plasmacytomas was also required. BOR was defined as the best sequential response, using the IRC's assessment of response, from the start of treatment until disease progression (provided that the progression is subsequently confirmed in case of progression requiring confirmation), death, initiation of further anti-myeloma treatment, or cut-off date, whichever occurs first.

  20. Percentage of Participants With Very Good Partial Response (VGPR) [ 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) ]
    VGPR rate was defined as the percentage of participants achieving a VGPR or better as BOR. VGPR was defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein level <100 mg/24 h or >=90% decrease in the sum of maximal perpendicular diameter compared to baseline in soft tissue plasmacytoma. BOR was defined as the best sequential response (CR), using the IRC's assessment of response, from the start of treatment until disease progression (provided that the progression is subsequently confirmed in case of progression requiring confirmation), death, initiation of further anti-myeloma treatment, or cut-off date, whichever occurs first. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates.

  21. Time to First Response (TT1R) [ 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) ]
    TT1R was defined as the time from randomization to the date of first IRC determined response (PR or better) that is subsequently confirmed. PR was defined as >=50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >=90% or to <200 mg/24 h. In addition to the above listed criteria, if present at baseline, a >=50% reduction in the size (SPD) of soft tissue plasmacytomas was also required.

  22. Time to Best Response (TTBR) [ 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) ]
    TTBR was defined as the time from randomization to the date of first occurrence of IRC determined BOR (PR or better) that was subsequently confirmed. PR was defined as >=50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >=90% or to <200 mg/24 h. In addition to the above listed criteria, if present at baseline, a >=50% reduction in the size (SPD) of soft tissue plasmacytomas was also required. BOR was defined as the best sequential response, using the IRC's assessment of response, from the start of treatment until disease progression (provided that the progression is subsequently confirmed in case of progression requiring confirmation), death, initiation of further anti-myeloma treatment, or cut-off date, whichever occurs first.

  23. Number of Participants With Minimal Residual Disease (MRD) [ Time Frame: Up to 76.7 weeks ]
    MRD was assessed by next-generation sequencing in bone marrow samples from participants who achieved CR, to determine the depth of response at the molecular level. IMWG criteria for CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow aspirates. MRD was classified as positive or negative at the minimum sensitivity of 1 in 10^5 nucleated cells. MRD negativity was defined as the absence of the dominant clonotype sequence(s) identified in the bone marrow aspirate collected at screening. MRD positivity was defined as the presence of the dominant clonotype sequence(s) identified in the bone marrow aspirate collected at screening.



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 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 x 10^9/L).
  • Creatinine clearance inferior to 30 mL per minute (Modification of Diet in Renal Disease [MDRD] Formula).
  • Total bilirubin superior to 2 x 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 x 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.


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


Locations
Show Show 111 study locations
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] June 11, 2019
Statistical Analysis Plan  [PDF] November 7, 2018

Publications:
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02990338    
Other Study ID Numbers: EFC14335
2016-003097-41 ( EudraCT Number )
U1111-1180-6262 ( Other Identifier: UTN )
First Posted: December 13, 2016    Key Record Dates
Results First Posted: December 6, 2019
Last Update Posted: August 12, 2020
Last Verified: August 2020
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
Keywords provided by Sanofi:
Anti-CD38 monoclonal antibody
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
Dexamethasone
Pomalidomide
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
Immunologic Factors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents