Clinical Trials List
Protocol NumberEFC14335
2017-04-01 - 2021-12-31
Phase III
Terminated4
ICD-10C90.00
Multiple myeloma not having achieved remission
A phase 3 randomized, open-label, multicenter study comparing isatuximab in combination with pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with refractory or relapsed and refractory multiple
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Trial Applicant
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Sponsor
Sanofi Taiwan Co., Ltd
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chien-Yuan Chen Division of Hematology & Oncology
- Sheng-chieh Chou Division of Hematology & Oncology
- MING YAO Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Po-Nan Wang Division of Hematology & Oncology
- Ming-Chung Kao Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Audit
None
Co-Principal Investigator
- Li-Yuan Bai Division of Hematology & Oncology
- Chen-Yuan Lin Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
- Che-Hung Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
multiple myeloma
Objectives
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).
Test Drug
Isatuximab
Active Ingredient
isatuximab
Dosage Form
Vial
Dosage
500mg/25ml
Endpoints
The primary endpoint is PFS. Progression free survival is defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) (as determined by the Independent Response Committee [IRC]) or the date of death from any cause, whichever comes first. Response will be determined according to International Myeloma Working Group (IMWG) criteria (1). Progression will be confirmed based on two consecutive assessments.
Inclution Criteria
l 01. Age ≥18 years or country’s legal age of majority if the legal age is >18 years old
l 02. Patients must have a documented diagnosis of multiple myeloma with evidence of measurable disease
- Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis
and/or
- Urine M protein ≥200 mg/24 hours measured using urine
protein immunoelectrophoresis
l 03. 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. Note: An induction treatment followed by autologous stem cell transplantation (ASCT) and consolidation/maintenance is considered as one line of treatment
l 04. Patients must have failed treatment with lenalidomide and
a proteasome inhibitor (bortezomib, carfilzomib or ixazomib) alone or in combination, defined by any of the following (failure to lenalidomide and a proteasome inhibitor can have occurred at any line of therapy):
Progression has occurred while on or within 60 days from end of
the treatment with lenalidomide and/or a proteasome inhibitor
In case of previous response ≥ partial response (PR) to
lenalidomide and/or a proteasome inhibitor, patient must have progressed within 6 months after discontinuation of the treatment
Patients who have developed intolerable toxicity after a minimum of 2 consecutive cycles of a regimen containing lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib or ixazomib) alone or in combination. Intolerance is defined as below:
- For proteasome inhibitor containing regimens: any toxicity leading to discontinuation of a proteasome inhibitor, like ≥G2 peripheral neuropathy or ≥G2 neuropathic pain. Peripheral neuropathy must be ≤G1 before study entry (according to NCI-CTCAE v4.03)
- For lenalidomide containing regimens: any toxicity leading to discontinuation of lenalidomide, like G3 rash. Rash must not have been G4 and other non-hematologic toxicities should not have been G4. All non-hematologic toxicities must be ≤G1 before study entry
l 05. Patients must have progressed on or within 60 days after end of previous therapy before to study entry, ie, refractory to the last line of treatment. This patient population includes the following two categories:
Refractory disease: patients who were refractory to all previous lines of treatment but should have achieved at least a minimal response (MR) in one previous line
Relapsed and refractory disease: patients who were relapsed from at least one previous line of treatment and refractory to the last line of treatment. Patients can be refractory to other previous line/lines of treatment
Note: Patients must have achieved a minimal response (MR) or better to at least one of the previous lines of treatment (ie, primary refractory disease is not eligible)
l 06. Patient has given voluntary written informed consent before performance of any study related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to his/her medical care
l 02. Patients must have a documented diagnosis of multiple myeloma with evidence of measurable disease
- Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis
and/or
- Urine M protein ≥200 mg/24 hours measured using urine
protein immunoelectrophoresis
l 03. 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. Note: An induction treatment followed by autologous stem cell transplantation (ASCT) and consolidation/maintenance is considered as one line of treatment
l 04. Patients must have failed treatment with lenalidomide and
a proteasome inhibitor (bortezomib, carfilzomib or ixazomib) alone or in combination, defined by any of the following (failure to lenalidomide and a proteasome inhibitor can have occurred at any line of therapy):
Progression has occurred while on or within 60 days from end of
the treatment with lenalidomide and/or a proteasome inhibitor
In case of previous response ≥ partial response (PR) to
lenalidomide and/or a proteasome inhibitor, patient must have progressed within 6 months after discontinuation of the treatment
Patients who have developed intolerable toxicity after a minimum of 2 consecutive cycles of a regimen containing lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib or ixazomib) alone or in combination. Intolerance is defined as below:
- For proteasome inhibitor containing regimens: any toxicity leading to discontinuation of a proteasome inhibitor, like ≥G2 peripheral neuropathy or ≥G2 neuropathic pain. Peripheral neuropathy must be ≤G1 before study entry (according to NCI-CTCAE v4.03)
- For lenalidomide containing regimens: any toxicity leading to discontinuation of lenalidomide, like G3 rash. Rash must not have been G4 and other non-hematologic toxicities should not have been G4. All non-hematologic toxicities must be ≤G1 before study entry
l 05. Patients must have progressed on or within 60 days after end of previous therapy before to study entry, ie, refractory to the last line of treatment. This patient population includes the following two categories:
Refractory disease: patients who were refractory to all previous lines of treatment but should have achieved at least a minimal response (MR) in one previous line
Relapsed and refractory disease: patients who were relapsed from at least one previous line of treatment and refractory to the last line of treatment. Patients can be refractory to other previous line/lines of treatment
Note: Patients must have achieved a minimal response (MR) or better to at least one of the previous lines of treatment (ie, primary refractory disease is not eligible)
l 06. Patient has given voluntary written informed consent before performance of any study related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to his/her medical care
Exclusion Criteria
E 01. Primary refractory multiple myeloma defined as: patients who have never achieved at least a MR with any treatment during the disease course
E 02. Free Light Chain measurable disease only
E 03. Patient with prior anti-CD38 monoclonal antibody treatment with progression on or within 60 days after end of anti-CD38 monoclonal antibody treatment or failure to achieve at least MR to treatment (ie, refractory to anti-CD38)
E 04. Prior therapy with pomalidomide
E 05. Any anti-myeloma drug treatment within 14 days before randomization, including dexamethasone
E 06. Prior allogenic hematopoietic stem cell (HSC) transplant with active graft versus host disease (GvHD) (GvHD any grade and/or being under immunosuppressive treatment within the last 2 months)
E 07. Any major procedure within 14 days before the initiation of the study treatment: plasmapheresis, major surgery (kyphoplasty is not considered a major procedure), radiotherapy
E 08. Patient who has received any other investigational drugs or prohibited therapy for this study within 28 days or 5 half-lives from randomization, whichever is longer
E 09. ECOG status >2
E 10. Platelets <75 000 cells/μL if <50% of bone marrow (BM) nucleated cells are plasma cells and, <30 000 cells/μL if ≥50% of BM nucleated cells are plasma cells. Platelet transfusion is not allowed within three days before the screening hematological test
E 11. ANC <1000 μ/L (1 x 109/L). The use of G-CSF is not allowed to reach this level
E 12. Creatinine clearance <30 mL/min (MDRD Formula, see Appendix A)
E 13. Total bilirubin >2 x ULN
E 14. Corrected serum calcium >14 mg/dL (>3.5 mmol/L)
E 15. AST and/or ALT>3 x ULN
E 16. Ongoing toxicity (excluding alopecia and those listed in eligibility criteria) from any prior anti-myeloma therapy >G1 (NCI-CTCAE v4.03)
E 17. 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 (see I 04)
E 18. 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
E 19. Significant cardiac dysfunction; myocardial infarction within 12 months; unstable, poorly controlled angina pectoris
E 20. 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, an in situ malignancy, or low risk prostate cancer after curative therapy
E 21. Known to be HIV+ or to have hepatitis A, B or C active infection
E 22. Malabsorption syndrome or any condition that can significantly impact the absorption of pomalidomide
E 23. Active primary amyloid-light (AL) amyloidosis (evidence of end organ damage or receiving treatment for amyloidosis)
E 24. Concomitant plasma cell leukemia
E 25. Unable or unwilling to undergo to thromboprophylaxis
E 26. Daily requirement for corticosteroids (equivalent to ≥10 mg/day of prednisone) for more than 7 days (except for inhalation corticosteroids)
E 27. Pregnant or breastfeeding female or female who intends to become pregnant during the participation in the study. Females of childbearing potential (FCBP) unwilling to prevent pregnancy by the use of 2 reliable methods of contraception for ≥4 weeks before the start of study treatment, during treatment (including dose interruptions), and up to 3 or 5 months following the last dose of study treatment for Pd and IPd respectively, and/or who are unwilling or unable to be tested for pregnancy before study treatment initiation (2 negative tests), weekly during 1st month of treatment and then prior each treatment cycle administration or every 2 weeks in case or irregular menstrual cycles up to 3 or 5 months following the last dose of study treatment for Pd and IPd respectively
E 28. Male participants who disagree to practice true abstinence or disagree to use a condom during sexual contact with a pregnant female or a FCBP while participating in the study, during dose interruptions and at least 3 or 5 months following study treatment discontinuation for Pd and IPd respectively, even if has undergone a successful vasectomy
Note 1: a FCBP is a female who: 1) has achieved menarche at some time point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months)
Note 2: True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
E 29. All patients who disagree to refrain from donating blood while on study treatment and for 4 weeks after discontinuation from this study treatment
E 30. All patients who do not agree to keep study treatment for their personal use only
E 31. Any country-related specific regulation that would prevent the patient from entering the study
E 32. Any severe acute or chronic medical condition which could impair the ability of the patient to participate in the study or interfere with interpretation of study results (eg, systemic infection unless specific anti-infective therapy is employed) or patient unable to comply with the study procedures
E 02. Free Light Chain measurable disease only
E 03. Patient with prior anti-CD38 monoclonal antibody treatment with progression on or within 60 days after end of anti-CD38 monoclonal antibody treatment or failure to achieve at least MR to treatment (ie, refractory to anti-CD38)
E 04. Prior therapy with pomalidomide
E 05. Any anti-myeloma drug treatment within 14 days before randomization, including dexamethasone
E 06. Prior allogenic hematopoietic stem cell (HSC) transplant with active graft versus host disease (GvHD) (GvHD any grade and/or being under immunosuppressive treatment within the last 2 months)
E 07. Any major procedure within 14 days before the initiation of the study treatment: plasmapheresis, major surgery (kyphoplasty is not considered a major procedure), radiotherapy
E 08. Patient who has received any other investigational drugs or prohibited therapy for this study within 28 days or 5 half-lives from randomization, whichever is longer
E 09. ECOG status >2
E 10. Platelets <75 000 cells/μL if <50% of bone marrow (BM) nucleated cells are plasma cells and, <30 000 cells/μL if ≥50% of BM nucleated cells are plasma cells. Platelet transfusion is not allowed within three days before the screening hematological test
E 11. ANC <1000 μ/L (1 x 109/L). The use of G-CSF is not allowed to reach this level
E 12. Creatinine clearance <30 mL/min (MDRD Formula, see Appendix A)
E 13. Total bilirubin >2 x ULN
E 14. Corrected serum calcium >14 mg/dL (>3.5 mmol/L)
E 15. AST and/or ALT>3 x ULN
E 16. Ongoing toxicity (excluding alopecia and those listed in eligibility criteria) from any prior anti-myeloma therapy >G1 (NCI-CTCAE v4.03)
E 17. 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 (see I 04)
E 18. 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
E 19. Significant cardiac dysfunction; myocardial infarction within 12 months; unstable, poorly controlled angina pectoris
E 20. 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, an in situ malignancy, or low risk prostate cancer after curative therapy
E 21. Known to be HIV+ or to have hepatitis A, B or C active infection
E 22. Malabsorption syndrome or any condition that can significantly impact the absorption of pomalidomide
E 23. Active primary amyloid-light (AL) amyloidosis (evidence of end organ damage or receiving treatment for amyloidosis)
E 24. Concomitant plasma cell leukemia
E 25. Unable or unwilling to undergo to thromboprophylaxis
E 26. Daily requirement for corticosteroids (equivalent to ≥10 mg/day of prednisone) for more than 7 days (except for inhalation corticosteroids)
E 27. Pregnant or breastfeeding female or female who intends to become pregnant during the participation in the study. Females of childbearing potential (FCBP) unwilling to prevent pregnancy by the use of 2 reliable methods of contraception for ≥4 weeks before the start of study treatment, during treatment (including dose interruptions), and up to 3 or 5 months following the last dose of study treatment for Pd and IPd respectively, and/or who are unwilling or unable to be tested for pregnancy before study treatment initiation (2 negative tests), weekly during 1st month of treatment and then prior each treatment cycle administration or every 2 weeks in case or irregular menstrual cycles up to 3 or 5 months following the last dose of study treatment for Pd and IPd respectively
E 28. Male participants who disagree to practice true abstinence or disagree to use a condom during sexual contact with a pregnant female or a FCBP while participating in the study, during dose interruptions and at least 3 or 5 months following study treatment discontinuation for Pd and IPd respectively, even if has undergone a successful vasectomy
Note 1: a FCBP is a female who: 1) has achieved menarche at some time point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months)
Note 2: True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
E 29. All patients who disagree to refrain from donating blood while on study treatment and for 4 weeks after discontinuation from this study treatment
E 30. All patients who do not agree to keep study treatment for their personal use only
E 31. Any country-related specific regulation that would prevent the patient from entering the study
E 32. Any severe acute or chronic medical condition which could impair the ability of the patient to participate in the study or interfere with interpretation of study results (eg, systemic infection unless specific anti-infective therapy is employed) or patient unable to comply with the study procedures
The Estimated Number of Participants
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Taiwan
8 participants
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Global
300 participants
