Clinical Trials List
Protocol Number54767414MMY3003
2014-07-01 - 2023-10-25
Phase III
Terminated4
ICD-10C90.02
Multiple myeloma in relapse
ICD-9203.01
Multiple myeloma, in remission
ICD-9203.00
Multiple myeloma, without mention of remission
Phase 3 Study Comparing Daratumumab, Lenalidomide, and Dexamethasone (DRd) vs Lenalidomide and Dexamethasone (Rd) in Subjects With Relapsed or Refractory Multiple Myeloma
-
Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
-
Sponsor
Janssen Research & Development
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chien-Yuan Chen Division of Hematology & Oncology
- MING YAO Division of Hematology & Oncology
- Sheng-chieh Chou Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Ming-Chung Kao Division of Hematology & Oncology
- Po-Nan Wang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Wei-Pang Chung Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Completed
Co-Principal Investigator
- Ming-Yu Lien Division of Hematology & Oncology
- Chen-Yuan Lin Division of Hematology & Oncology
- Ching-Chan Lin Division of Hematology & Oncology
- Li-Yuan Bai Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
7 Stop recruiting
Condition/Disease
Relapsed or Refractory Multiple Myeloma
Objectives
The primary objective is to compare the efficacy of daratumumab when combined with lenalidomide and
dexamethasone (DRd) to that of lenalidomide and dexamethasone (Rd), in terms of progression-free
survival (PFS) in subjects with relapsed or refractory multiple myeloma
Test Drug
Daratumumab
Active Ingredient
Daratumumab
Dosage Form
5ml/vial
Dosage
20
Endpoints
Primary Endpoint
The primary endpoint is PFS, which is defined as the duration from the date of randomization to
either progressive disease, according to the IMWG criteria (Durie 200611, Rajkumar 201131), or
death, whichever occurs first. For subjects who have not progressed and are alive, data will be
censored at the last disease evaluation before the start of any subsequent anti-myeloma therapy.
Relapse from CR by positive immunofixation or trace amount of M-protein is not considered to
be progressive disease and is not included in the PFS calculation.
The primary analysis data cutoff date will occur once the targeted number of PFS events (295) is
reached. At that time, for subjects without disease progression, disease assessments will continue
but will be performed according to the standard of care.
Secondary Endpoints
The secondary efficacy endpoints include:
• Time to disease progression, defined as the time from the date of randomization to the date
of first documented evidence of PD, as defined in the IMWG criteria. For subjects who have
not progressed, data will be censored at the date of the disease evaluation before the start of
any subsequent anti-myeloma therapy.
• Overall response rate, defined as the proportion of subjects who achieve CR or PR according
to the IMWG criteria, during or after the study treatment.
• Proportion of subjects who achieve VGPR or better, defined as the proportion of subjects
achieving VGPR and CR (including sCR) according to the IMWG criteria during or after the
study treatment at the time of data cutoff.
• Time to response, defined as the time between the date of randomization and the first
efficacy evaluation that the subject has met all criteria for CR or PR. For subjects without
response (CR/PR), data will be censored either at the date of progressive disease or, in the
absence of progressive disease, at the last disease evaluation before the start of subsequent
anti-myeloma therapy.
• Duration of response will be calculated from the date of initial documentation of a response
(CR or PR) to the date of first documented evidence of progressive disease, as defined in the
IMWG criteria. For subjects who have not progressed, data will be censored at the last
disease evaluation before the start of any subsequent anti-myeloma therapy.
• Overall survival is measured from the date of randomization to the date of the subject’s
death. If the subject is alive or the vital status is unknown, then the subject’s data will be
censored at the date the subject was last known to be alive.
The primary endpoint is PFS, which is defined as the duration from the date of randomization to
either progressive disease, according to the IMWG criteria (Durie 200611, Rajkumar 201131), or
death, whichever occurs first. For subjects who have not progressed and are alive, data will be
censored at the last disease evaluation before the start of any subsequent anti-myeloma therapy.
Relapse from CR by positive immunofixation or trace amount of M-protein is not considered to
be progressive disease and is not included in the PFS calculation.
The primary analysis data cutoff date will occur once the targeted number of PFS events (295) is
reached. At that time, for subjects without disease progression, disease assessments will continue
but will be performed according to the standard of care.
Secondary Endpoints
The secondary efficacy endpoints include:
• Time to disease progression, defined as the time from the date of randomization to the date
of first documented evidence of PD, as defined in the IMWG criteria. For subjects who have
not progressed, data will be censored at the date of the disease evaluation before the start of
any subsequent anti-myeloma therapy.
• Overall response rate, defined as the proportion of subjects who achieve CR or PR according
to the IMWG criteria, during or after the study treatment.
• Proportion of subjects who achieve VGPR or better, defined as the proportion of subjects
achieving VGPR and CR (including sCR) according to the IMWG criteria during or after the
study treatment at the time of data cutoff.
• Time to response, defined as the time between the date of randomization and the first
efficacy evaluation that the subject has met all criteria for CR or PR. For subjects without
response (CR/PR), data will be censored either at the date of progressive disease or, in the
absence of progressive disease, at the last disease evaluation before the start of subsequent
anti-myeloma therapy.
• Duration of response will be calculated from the date of initial documentation of a response
(CR or PR) to the date of first documented evidence of progressive disease, as defined in the
IMWG criteria. For subjects who have not progressed, data will be censored at the last
disease evaluation before the start of any subsequent anti-myeloma therapy.
• Overall survival is measured from the date of randomization to the date of the subject’s
death. If the subject is alive or the vital status is unknown, then the subject’s data will be
censored at the date the subject was last known to be alive.
Inclution Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study.
1. Subject must be at least 18 years of age.
2. Subject must have documented multiple myeloma as defined by the criteria below:
• Monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven
plasmacytoma.
• Measurable disease as defined by any of the following:
- Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein
level ≥200 mg/24 hours; or
- IgA multiple myeloma: serum M-protein level ≥0.5 g/dL or urine M-protein level
≥200 mg/24 hours; or
- Light chain multiple myeloma: Serum immunoglobulin free light chain ≥10 mg/dL
and abnormal serum immunoglobulin kappa lambda free light chain ratio.
3. Subject must have received at least 1 prior line of therapy for multiple myeloma (refer to
Attachment 1).
4. Subject must have achieved a response (PR or better) to at least one prior regimen (refer to
Attachment 1).
5. Subject must have documented evidence of progressive disease (PD) as defined by the
IMWG criteria on or after their last regimen.
6. Subject must have an ECOG Performance Status score of 0, 1, or 2 (refer to Attachment 2).
7. For subjects experiencing toxicities resulting from previous therapy (including peripheral
neuropathy), the toxicities must have resolved or stabilized to ≤Grade 1.
8. Women of childbearing potential must commit to either abstain continuously from
heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously.
This includes one highly effective form of contraception (tubal ligation, intrauterine device
[IUD], hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants]
or partner’s vasectomy) and one additional effective contraceptive method (male latex or
synthetic condom, diaphragm, or cervical cap). Contraception must begin 4 weeks prior to
dosing. Reliable contraception is indicated even where there has been a history of infertility,
unless due to hysterectomy.
9. A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at
Screening, first within 10 to 14 days prior to dosing and the second within 24 hours prior to
dosing. For requirements during the Treatment Phase, please see Section 4.3.
10. Each subject (or their legally acceptable representative) must sign an informed consent form
(ICF) indicating that he or she understands the purpose of and procedures required for the
study and are willing to participate in the study. Subjects must be willing and able to adhere
to the prohibitions and restrictions specified in this protocol, as referenced in the ICF.
1. Subject must be at least 18 years of age.
2. Subject must have documented multiple myeloma as defined by the criteria below:
• Monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven
plasmacytoma.
• Measurable disease as defined by any of the following:
- Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein
level ≥200 mg/24 hours; or
- IgA multiple myeloma: serum M-protein level ≥0.5 g/dL or urine M-protein level
≥200 mg/24 hours; or
- Light chain multiple myeloma: Serum immunoglobulin free light chain ≥10 mg/dL
and abnormal serum immunoglobulin kappa lambda free light chain ratio.
3. Subject must have received at least 1 prior line of therapy for multiple myeloma (refer to
Attachment 1).
4. Subject must have achieved a response (PR or better) to at least one prior regimen (refer to
Attachment 1).
5. Subject must have documented evidence of progressive disease (PD) as defined by the
IMWG criteria on or after their last regimen.
6. Subject must have an ECOG Performance Status score of 0, 1, or 2 (refer to Attachment 2).
7. For subjects experiencing toxicities resulting from previous therapy (including peripheral
neuropathy), the toxicities must have resolved or stabilized to ≤Grade 1.
8. Women of childbearing potential must commit to either abstain continuously from
heterosexual sexual intercourse or to use 2 methods of reliable birth control simultaneously.
This includes one highly effective form of contraception (tubal ligation, intrauterine device
[IUD], hormonal [birth control pills, injections, hormonal patches, vaginal rings or implants]
or partner’s vasectomy) and one additional effective contraceptive method (male latex or
synthetic condom, diaphragm, or cervical cap). Contraception must begin 4 weeks prior to
dosing. Reliable contraception is indicated even where there has been a history of infertility,
unless due to hysterectomy.
9. A woman of childbearing potential must have 2 negative serum or urine pregnancy tests at
Screening, first within 10 to 14 days prior to dosing and the second within 24 hours prior to
dosing. For requirements during the Treatment Phase, please see Section 4.3.
10. Each subject (or their legally acceptable representative) must sign an informed consent form
(ICF) indicating that he or she understands the purpose of and procedures required for the
study and are willing to participate in the study. Subjects must be willing and able to adhere
to the prohibitions and restrictions specified in this protocol, as referenced in the ICF.
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating
in the study.
1. Subject has received daratumumab or other anti-CD38 therapies previously.
2. Subject’s disease shows evidence of refractoriness or intolerance to lenalidomide. If
previously treated with a lenalidomide-containing regimen, the subject is excluded if he or
she:
• Discontinued due to any adverse event related to prior lenalidomide treatment, or
• If, at any time point, the subject was refractory to any dose of lenalidomide. Refractory
to lenalidomide is defined either:
o Subjects whose disease progresses within 60 days of lenalidomide; or
o Subjects whose disease is nonresponsive while on lenalidomide. Nonresponsive
disease is defined as either failure to achieve at least an MR or development of PD
while on lenalidomide.
3. Subject has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives
of the treatment, whichever is longer, before the date of randomization. This includes
subjects who have received a cumulative dose of corticosteroid greater than or equal to the
equivalence of 140 mg prednisone or a single dose of corticosteroid greater than or equal to
the equivalence of 40 mg/day dexamethasone within the 2-week period before Cycle 1,
Day 1. A list of anti-myeloma treatments with the corresponding pharmacokinetic half-lives
is provided in the Site Investigational Product Procedures Manual (IPPM).
4. Subject has received ASCT within 12 weeks before the date of randomization, or the subject
has previously received an allogenic stem cell transplant (regardless of timing).
5. Subjects planning to undergo a stem cell transplant prior to progression of disease on this
study, ie, these subjects should not be enrolled in order to reduce disease burden prior to
transplant.
6. Subject has a history of malignancy (other than multiple myeloma) within 3 years before the
date of randomization (exceptions are squamous and basal cell carcinomas of the skin and
carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with
concurrence with the sponsor's medical monitor, is considered cured with minimal risk of
recurrence within 3 years).
7. Subject has known meningeal involvement of multiple myeloma.
8. Subject has known chronic obstructive pulmonary disease (COPD) (defined as a forced
expiratory volume in 1 second (FEV1) <60% of predicted normal), asthma, or a history of
asthma within the last 2 years. Subjects with known or suspected COPD must have a forced
expiratory volume (FEV) test during Screening.
9. Subject is known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B
(defined by a positive test for hepatitis B surface antigen [HBsAg] or antibodies to hepatitis
B surface and core antigens [anti-HBs and anti-HBc, respectively]) or hepatitis C (anti-HCV
antibody positive or HCV-RNA quantitation positive).
10. Subject has any concurrent medical condition or disease (eg, active systemic infection) that
is likely to interfere with study procedures or results, or that in the opinion of the
investigator would constitute a hazard for participating in this study.
11. Subject has clinically significant cardiac disease, including:
• Myocardial infarction within 6 months before Cycle 1, Day 1, or unstable or
uncontrolled disease/condition related to or affecting cardiac function (eg, unstable
angina, congestive heart failure, New York Heart Association Class III-IV)
• Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE]
Version 4 Grade 2 or higher) or clinically significant ECG abnormalities.
• Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia’s
formula (QTcF) >500 msec.
12. Subject has any of the following laboratory test results during the Screening Phase:
• Absolute neutrophil count ≤1.0 × 109
/L;
• Hemoglobin level ≤7.5 g/dL (≤5 mmol/L) (it is not permissible to transfuse a subject to
reach this level);
• Platelet count <75 × 109
/L for subjects in whom <50% of bone marrow nucleated cells
are plasma cells; otherwise platelet count <50 × 109
/L (it is not permissible to transfuse a
subject to reach this level);
• Alanine aminotransferase level ≥2.5 times the upper limit of normal (ULN);
• Alkaline phosphatase level ≥2.5 × ULN;
• Total bilirubin level ≥2 × ULN, (except for Gilbert Syndrome: direct bilirubin 2 ×
ULN);
• Creatinine clearance ≤30 mL/min (for lenalidomide dose adjustment for subjects with
creatinine clearance 30-60 mL/min, please see Section 6.5). Calculated creatinine
clearance may be calculated using the Cockcroft-Gault formula provided in
Attachment 3;
• Potassium level <3.0 mEq/L; or
• Corrected serum calcium >14.0 mg/dL (3.5 mmol/L).
13. Subject has known allergies, hypersensitivity, or intolerance to monoclonal antibodies or
human proteins, or their excipients (refer to IB Daratumumab 201315), or known sensitivity
to mammalian-derived products.
14. Subject has plasma cell leukemia (>2.0 × 109
/L circulating plasma cells by standard
differential) or Waldenström’s macroglobulinemia or POEMS syndrome (polyneuropathy,
organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis.
15. Subject is known or suspected of not being able to comply with the study protocol
(eg, because of alcoholism, drug dependency, or psychological disorder) or the subject has
any condition for which, in the opinion of the investigator, participation would not be in the
best interest of the subject (eg, compromise their well-being) or that could prevent, limit, or
confound the protocol-specified assessments.
16. Subject is a woman who is pregnant or breastfeeding or planning to become pregnant while
enrolled in this study or within 4 weeks after the last dose of lenalidomide and within
6 months after the last dose of daratumumab.
17. Subject has received an investigational drug (including investigational vaccines) or used an
invasive investigational medical device within 4 weeks before randomization (except for
investigational anti-myeloma agents, which cannot be taken within 2 weeks prior to
randomization, as described in exclusion criterion #3).
18. Subject has had major surgery within 2 weeks before randomization, or will not have fully
recovered from surgery, or has surgery planned during the time the subject is expected to
participate in the study or within 2 weeks after the last dose of study treatment.
Note: subjects with planned surgical procedures to be conducted under local anesthesia may
participate.
in the study.
1. Subject has received daratumumab or other anti-CD38 therapies previously.
2. Subject’s disease shows evidence of refractoriness or intolerance to lenalidomide. If
previously treated with a lenalidomide-containing regimen, the subject is excluded if he or
she:
• Discontinued due to any adverse event related to prior lenalidomide treatment, or
• If, at any time point, the subject was refractory to any dose of lenalidomide. Refractory
to lenalidomide is defined either:
o Subjects whose disease progresses within 60 days of lenalidomide; or
o Subjects whose disease is nonresponsive while on lenalidomide. Nonresponsive
disease is defined as either failure to achieve at least an MR or development of PD
while on lenalidomide.
3. Subject has received anti-myeloma treatment within 2 weeks or 5 pharmacokinetic half-lives
of the treatment, whichever is longer, before the date of randomization. This includes
subjects who have received a cumulative dose of corticosteroid greater than or equal to the
equivalence of 140 mg prednisone or a single dose of corticosteroid greater than or equal to
the equivalence of 40 mg/day dexamethasone within the 2-week period before Cycle 1,
Day 1. A list of anti-myeloma treatments with the corresponding pharmacokinetic half-lives
is provided in the Site Investigational Product Procedures Manual (IPPM).
4. Subject has received ASCT within 12 weeks before the date of randomization, or the subject
has previously received an allogenic stem cell transplant (regardless of timing).
5. Subjects planning to undergo a stem cell transplant prior to progression of disease on this
study, ie, these subjects should not be enrolled in order to reduce disease burden prior to
transplant.
6. Subject has a history of malignancy (other than multiple myeloma) within 3 years before the
date of randomization (exceptions are squamous and basal cell carcinomas of the skin and
carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with
concurrence with the sponsor's medical monitor, is considered cured with minimal risk of
recurrence within 3 years).
7. Subject has known meningeal involvement of multiple myeloma.
8. Subject has known chronic obstructive pulmonary disease (COPD) (defined as a forced
expiratory volume in 1 second (FEV1) <60% of predicted normal), asthma, or a history of
asthma within the last 2 years. Subjects with known or suspected COPD must have a forced
expiratory volume (FEV) test during Screening.
9. Subject is known to be seropositive for human immunodeficiency virus (HIV) or hepatitis B
(defined by a positive test for hepatitis B surface antigen [HBsAg] or antibodies to hepatitis
B surface and core antigens [anti-HBs and anti-HBc, respectively]) or hepatitis C (anti-HCV
antibody positive or HCV-RNA quantitation positive).
10. Subject has any concurrent medical condition or disease (eg, active systemic infection) that
is likely to interfere with study procedures or results, or that in the opinion of the
investigator would constitute a hazard for participating in this study.
11. Subject has clinically significant cardiac disease, including:
• Myocardial infarction within 6 months before Cycle 1, Day 1, or unstable or
uncontrolled disease/condition related to or affecting cardiac function (eg, unstable
angina, congestive heart failure, New York Heart Association Class III-IV)
• Cardiac arrhythmia (Common Terminology Criteria for Adverse Events [CTCAE]
Version 4 Grade 2 or higher) or clinically significant ECG abnormalities.
• Screening 12-lead ECG showing a baseline QT interval as corrected by Fridericia’s
formula (QTcF) >500 msec.
12. Subject has any of the following laboratory test results during the Screening Phase:
• Absolute neutrophil count ≤1.0 × 109
/L;
• Hemoglobin level ≤7.5 g/dL (≤5 mmol/L) (it is not permissible to transfuse a subject to
reach this level);
• Platelet count <75 × 109
/L for subjects in whom <50% of bone marrow nucleated cells
are plasma cells; otherwise platelet count <50 × 109
/L (it is not permissible to transfuse a
subject to reach this level);
• Alanine aminotransferase level ≥2.5 times the upper limit of normal (ULN);
• Alkaline phosphatase level ≥2.5 × ULN;
• Total bilirubin level ≥2 × ULN, (except for Gilbert Syndrome: direct bilirubin 2 ×
ULN);
• Creatinine clearance ≤30 mL/min (for lenalidomide dose adjustment for subjects with
creatinine clearance 30-60 mL/min, please see Section 6.5). Calculated creatinine
clearance may be calculated using the Cockcroft-Gault formula provided in
Attachment 3;
• Potassium level <3.0 mEq/L; or
• Corrected serum calcium >14.0 mg/dL (3.5 mmol/L).
13. Subject has known allergies, hypersensitivity, or intolerance to monoclonal antibodies or
human proteins, or their excipients (refer to IB Daratumumab 201315), or known sensitivity
to mammalian-derived products.
14. Subject has plasma cell leukemia (>2.0 × 109
/L circulating plasma cells by standard
differential) or Waldenström’s macroglobulinemia or POEMS syndrome (polyneuropathy,
organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis.
15. Subject is known or suspected of not being able to comply with the study protocol
(eg, because of alcoholism, drug dependency, or psychological disorder) or the subject has
any condition for which, in the opinion of the investigator, participation would not be in the
best interest of the subject (eg, compromise their well-being) or that could prevent, limit, or
confound the protocol-specified assessments.
16. Subject is a woman who is pregnant or breastfeeding or planning to become pregnant while
enrolled in this study or within 4 weeks after the last dose of lenalidomide and within
6 months after the last dose of daratumumab.
17. Subject has received an investigational drug (including investigational vaccines) or used an
invasive investigational medical device within 4 weeks before randomization (except for
investigational anti-myeloma agents, which cannot be taken within 2 weeks prior to
randomization, as described in exclusion criterion #3).
18. Subject has had major surgery within 2 weeks before randomization, or will not have fully
recovered from surgery, or has surgery planned during the time the subject is expected to
participate in the study or within 2 weeks after the last dose of study treatment.
Note: subjects with planned surgical procedures to be conducted under local anesthesia may
participate.
The Estimated Number of Participants
-
Taiwan
20 participants
-
Global
560 participants
