Relapsed Refractory Multiple Myeloma
Conditions
Brief summary
To characterize safety associated with the use of Kyprolis under the locally approved label.
Detailed description
Kyprolis® (K; carfilzomib) was approved in India on 17 January 2017 as a prescription medication in combination with dexamethasone (Kd) or with lenalidomide (Revlimid®) plus dexamethasone (KRd) for the treatment of patients with relapsed or refractory multiple myeloma (RRMM) following 1 to 3 prior lines of therapy. This non-comparative, interventional phase 4 study is designed to fulfil the post-marketing requirement to assess safety, tolerability, and efficacy of Kyprolis on Indian subjects with RRMM as per the locally approved label.
Interventions
DRUGDrug: Carfilzomib + Dexamethasone
Drug: Carfilzomib + Dexamethasone * Carfilzomib will be administered as a 30-minute infusion. * Dexamethasone will be taken by mouth or intravenously.
DRUGDrug: Carfilzomib + Lenalidomide + Dexamethasone
Drug: Carfilzomib + Lenalidomide + Dexamethasone * Carfilzomib will be administered as a 10 minute infusion. * Lenalidomide will be taken orally. * Dexamethasone will be taken by mouth or intravenously.
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documented RRMM after last treatment. Refractory is defined as meeting 1 or more of the following: Nonresponsive to most recent therapy (stable disease \[SD\] or progressive disease \[PD\]) while on treatment, or Disease progression within 60 days of discontinuation from the most recent therapy. * Eligible to receive Kyprolis per the locally approved label. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. * Adequate hepatic function within 28 days prior to enrollment: bilirubin \< 1.5 times the upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 times the ULN. * Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9 /L within 28 days prior to enrollment. (Screening ANC should be independent of granulocyte- and granulocyte macrophage-colony stimulating factor support for at least 1 week and of pegylated granulocyte stimulating factor for ≥ 2 weeks). * Hemoglobin ≥ 80 g/L within 28 days prior to enrollment. Subjects should not have received red blood cell (RBC) transfusions for at least 7 days prior to obtaining the screening hemoglobin. * Platelet count ≥ 75 x 10\^9/L (≥ 50 x 10\^9/L if myeloma involvement in the bone marrow is ≥ 50%) within 28 days prior to enrollment. Subjects should not have received platelet transfusions for at least 7 days prior to obtaining the screening platelet count. * Adequate renal function within 28 days prior to enrollment (either measured or calculated using a standard formula such as the Cockcroft and Gault): calculated or measured creatinine clearance (CrCl) of ≥ 50 mL/min for subjects receiving KRd; calculated or measured CrCl of ≥ 15 mL/min for subjects receiving Kd. * Left ventricular ejection fraction ≥ 40% as assessed by transthoracic echocardiogram (TTE) or multigated acquisition scan (MUGA). * Females of childbearing potential (FCBP) must have a negative serum pregnancy test within the 10 to 14 days prior to enrollment and a negative urine pregnancy test within the 24 hours prior to day 1 of each cycle prior to dosing. * Subject or legally acceptable representative has provided informed consent/assent prior to initiation of any study specific activities/procedures.
Exclusion criteria
* Waldenström macroglobulinemia. * Plasma cell leukemia (\> 2.0 x 10\^9/L circulating plasma cells by standard differentials). * POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) * Myelodysplastic síndrome. * Primary amyloidosis (subjects with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all other criteria are met). * History of other malignancy within the past 5 years, with the following exception\[s\]: Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. Adequately treated cervical carcinoma in situ without evidence of disease. Adequately treated breast ductal carcinoma in situ without evidence of disease. Prostatic intraepithelial neoplasia without evidence of prostate cáncer. Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ. * Known immediate or delayed hypersensitivity reaction to Captisol (a cyclodextrin derivative used to solubilize Kyprolis). * Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs. * Intolerance to hydration. * Active congestive heart failure (New York Heart Association \[NYHA\] Class III to IV), symptomatic ischemia, uncontrolled arrhythmias, clinically significant echocardiogram (ECHO) abnormalities, screening ECG with corrected QT interval (QTc) of \> 470 msec, pericardial disease, or myocardial infarction within 4 months prior to enrollment. * Infiltrative pulmonary disease and/or known pulmonary hypertension. * Active infection within 14 days prior to enrollment requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents. Such infections must be fully resolved prior to initiating study treatment. * Pleural effusions requiring thoracentesis within 14 days prior to enrollment. * Ascites requiring paracentesis within 14 days prior to enrollment. * Uncontrolled hypertension, defined as an average systolic blood pressure \> 159 mmHg or diastolic \> 99 mm/Hg despite optimal treatment (measured following European Society of Hypertension/European Society of Cardiology \[ESH/ESC\] 2013 guidelines. * Active hepatitis B virus (HBV) infection. Subjects with positive hepatitis B surface antigen (HBsAg) or core antibody (anti-HBc) that achieve sustained virologic response with antiviral therapy directed at hepatitis B are allowed. Subjects with known history or resolved infection (negative for HBsAg but positive for antibodies to surface antigen, and/or core antigen) must be screened with HBV DNA levels. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (hepatitis B surface antibody \[anti-HBs\] positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA. * Known human immunodeficiency virus (HIV) infection, hepatitis C infection (subjects with hepatitis C that achieve a sustained virologic response following antiviral therapy are allowed). * Ongoing graft-versus-host disease. * Subjects with grade 3 or worse neuropathy within 14 days prior to enrollment. * Antitumor therapy (eg, chemotherapy, immunotherapy, antibody therapy) or investigational agent within 28 days before enrollment or not recovered from any acute toxicity. * Subjects on immunosuppressive therapy for graft versus host disease, even if it has resolved. * Glucocorticoid therapy within 14 days before first dose that exceeds a cumulative dose of 160 mg or dexamethasone or equivalent dose of other corticosteroids. * Focal radiation therapy within 7 days before enrollment. Radiation therapy to an extended field involving significant volume of bone marrow within 28 days prior to enrollment (ie, prior radiation must have been to less than 30% of the bone marrow). * Autologous stem cell transplant less than 100 days prior to enrollment. * Prior treatment with Kyprolis (carfilzomib). * Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study. Other investigational procedures while participating in this study are excluded. * Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment, during any breaks (interruptions) in the treatment, and for an additional 30 days after the last dose of Kyprolis. Females of childbearing potential should only be included in the study after a confirmed menstrual period and a negative highly sensitive urine or serum pregnancy test. * Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment, during any breaks (interruptions) in the treatment, and for an additional 30 days after the last dose of Kyprolis. NOTE: Female subjects of childbearing potential being treated with lenalidomide must agree to use 2 methods of contraception for at least 28 days before starting treatment, during treatment, during any breaks (interruptions) in the treatment, and for an additional 30 days after the last dose of treatment. • Male subjects with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 90 days after the last dose of Kyprolis. NOTE: Male subjects being treated with lenalidomide must agree to use a male condom with spermicide even if they have undergone a successful vasectomy. * Male subjects with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 90 days after the last dose of Kyprolis. * Male subjects unwilling to abstain from donating sperm during treatment and for an additional 90 days after the last dose of Kyprolis. * Subject likely to not be available to complete all protocol required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge. * History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. * Active hepatitis B virus (HBV) infection. Subjects with positive hepatitis B surface antigen (HBsAg) or core antibody (anti-HBc) that achieve sustained virologic response with antiviral therapy directed at hepatitis B are allowed. Subjects with known history or resolved infection (negative for HBsAg but positive for antibodies to surface antigen, and/or core antigen) must be screened with HBV DNA levels. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (hepatitis B surface antibody \[anti-HBs\] positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | From the first dose date of any IP until the end of trial; median (min, max) time on trial was 8.7 (0.1, 37.2) months | A TEAE was any untoward medical occurrence in a clinical trial participant after the first dose of investigational product (IP) irrespective of a causal relationship with the IP. TEAEs were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.03. Any clinically significant laboratory changes over time were recorded as TEAEs. |
| Number of Participants Who Experienced Serious TEAEs | From the first dose date of any IP until the end of trial; median (min, max) time on trial was 8.7 (0.1, 37.2) months | A serious TEAE was any untoward medical occurrence in a clinical trial participant after first dose of IP irrespective of a causal relationship with the IP(s), that resulted in death, was immediately life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or another medically important serious event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) as Per International Myeloma Working Group-Uniform Response Criteria (IMWG-URC) | From enrollment until the end of trial or death date, whichever occurred earlier; median (min, max) time on trial was 8.7 (0.1, 37.2) months | PFS was defined as the time from first dose of IP until the earliest date of disease progression (PD) or death due to any cause. PD was per IMWG-URC, with progression assessments at intervals as per local standard of care. PD: increase of 25% from lowest response value in serum M-component and/or urine M-component and/or only in participants without measurable serum and urine M protein levels: the difference between involved and uninvolved free light chain (FLC) levels and/or only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow (BM) plasma cell percentage; definite development of new bone lesions or soft tissue plasmacytomas; development of hypercalcemia. Medians were estimated using the Kaplan-Meier method. Corresponding 95% confidence intervals (CIs) were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. |
| Overall Response Rate (ORR) as Per IMWG-URC | From the first dose date of any IP until the end of trial; median (min, max) time on trial was 8.7 (0.1, 37.2) months | ORR was defined as the percentage of participants for whom the best overall response was a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) as determined by the IMWG-URC. CR: negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, \< 5% plasma cells in bone marrow (BM). sCR: CR and normal serum free light chain ratio and no clonal cells in BM by immunohistochemistry. VGPR: Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level \< 100 mg/24-hours). PR: ≥ 50% reduction of serum M-protein and reduction in 24-hours urinary M-protein by ≥ 90% or to \< 200 mg/24-hours. The ORR 95% CIs were estimated using the Clopper-Pearson method. |
| Clinical Benefit Rate (CBR) as Per IMWG-URC | From the first dose date of any IP until the end of trial; median (min, max) time on trial was 8.7 (0.1, 37.2) months | CBR was defined as the percentage of participants with either the best overall response of sCR, CR, VGPR, PR, and minimal response (MR) as determined by the IMWG-URC. CR: negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, \< 5% plasma cells in BM. sCR: CR and normal serum free light chain ratio and no clonal cells in BM by immunohistochemistry. VGPR: Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level \< 100 mg/24-hours). PR: ≥ 50% reduction of serum M-protein and reduction in 24-hours urinary M-protein by ≥ 90% or to \< 200 mg/24-hours. MR: ≥ 25% but ≤ 49% reduction of serum M-protein and reduction in 24-hour urinary M-protein by 50% to 89%. The CBR 95% CIs were estimated using the Clopper-Pearson method. |
| Time to Response (TTR) as Per IMWG-URC | From the first dose date of any IP until the end of trial; median (min, max) time on trial was 8.7 (0.1, 37.2) months | TTR was defined as the time from first dose date to the earliest date when confirmed sCR, CR, VGPR, or PR was first achieved. CR: negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, \< 5% plasma cells in BM. sCR: CR and normal serum free light chain ratio and no clonal cells in BM by immunohistochemistry. VGPR: Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level \< 100 mg/24-hours). PR: ≥ 50% reduction of serum M-protein and reduction in 24-hours urinary M-protein by ≥ 90% or to \< 200 mg/24-hours. Medians were estimated using the Kaplan-Meier method. |
| Duration of Response (DOR) as Per IMWG-URC | From enrollment until the end of trial or death date, whichever occurred earlier; median (min, max) time on trial was 8.7 (0.1, 37.2) months | DOR was defined as the time from first evidence of PR or better as per IMWG-URC to the earliest of PD or death due to any cause for participants with a best response of PR or better. PD: increase of 25% from lowest response value in serum M-component and/or urine M-component and/or only in participants without measurable serum and urine M protein levels: the difference between involved and uninvolved FLC levels and/or only in participants without measurable serum and urine M-protein levels and without measurable disease by FLC levels, bone marrow plasma cell percentage; definite development of new bone lesions or soft tissue plasmacytomas; development of hypercalcemia. Medians were estimated using the Kaplan-Meier method. Corresponding 95% CIs were estimated using the method by Klein and Moeschberger (1997) with log-log transformation. |
Countries
India
Contacts
STUDY_DIRECTORMD
Amgen
Participant flow
Recruitment details
101 participants were enrolled at 15 centers in India between September 2019 and June 2025.
Pre-assignment details
Screening assessments were conducted within 28 days before enrollment into the trial.
Participants by arm
| Arm | Count |
|---|---|
| Carfilzomib, Lenalidomide and Dexamethasone (KRd) Participants with relapsed or refractory multiple myeloma received a triplet combination of KRd.
Carfilzomib was administered as a 10-minute intravenous (IV) infusion on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day treatment cycles. The starting dose of carfilzomib was 20 mg/m\^2 on Days 1 and 2, and if tolerated, escalated to a target dose of 27 mg/m\^2 starting on Day 8 of cycle 1 and thereafter. From cycle 13, the Day 8 and Day 9 doses of carfilzomib were omitted. After cycle 18, carfilzomib was discontinued.
Lenalidomide 25 mg was taken orally on Days 1 to 21 and dexamethasone 40 mg by mouth or IV infusion on Days 1, 8, 15, and 22 of repeated 28-day treatment cycles. | 49 |
| Carfilzomib and Dexamethasone (Kd) Participants with relapsed or refractory multiple myeloma received a doublet combination of Kd.
Carfilzomib was administered as a 30-minute IV infusion on Days 1, 2, 8, 9, 15, and 16 of repeated 28-day treatment cycles. The starting dose of carfilzomib was 20 mg/m\^2 on Days 1 and 2, and if tolerated, was escalated to a target dose of 56 mg/m\^2 starting on Day 8 of cycle 1 and thereafter.
Dexamethasone 20 mg was taken by mouth or intravenously on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. | 52 |
| Total | 101 |
Baseline characteristics
| Characteristic | Carfilzomib and Dexamethasone (Kd) | Total | Carfilzomib, Lenalidomide and Dexamethasone (KRd) |
|---|---|---|---|
| Age, Continuous | 61.9 years STANDARD_DEVIATION 9.9 | 59.6 years STANDARD_DEVIATION 9.3 | 57.2 years STANDARD_DEVIATION 8.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 101 Participants | 49 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 52 Participants | 101 Participants | 49 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 15 Participants | 32 Participants | 17 Participants |
| Sex: Female, Male Male | 37 Participants | 69 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 49 | 2 / 52 |
| other Total, other adverse events | 45 / 49 | 42 / 52 |
| serious Total, serious adverse events | 11 / 49 | 20 / 52 |
Outcome results
Primary
Number of Participants Who Experienced Serious TEAEs
A serious TEAE is any untoward medical occurrence in a clinical study participant after first dose irrespective of a causal relationship with the study treatment(s) that resulted in death, was immediately life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or another medically important serious event.
Time frame: From the first dose date of any study drug until the end of study or cutoff date, whichever occurred earlier (median [min, max] time on treatment was 43.14 [4.4, 73.4] weeks for the KRd group and 28.79 [0.3, 107.3] weeks for the Kd group)
Population: Measured in the safety analysis set, which included all enrolled participants who received at least one dose of the investigational product(s).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Carfilzomib, Lenalidomide and Dexamethasone (KRd) | Number of Participants Who Experienced Serious TEAEs | 12 Participants |
| Carfilzomib and Dexamethasone (Kd) | Number of Participants Who Experienced Serious TEAEs | 19 Participants |
Primary
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
A TEAE is any untoward medical occurrence in a clinical study participant after first dose irrespective of a causal relationship with the study treatment(s). TEAEs were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.4.03. Any clinically significant laboratory changes over time were recorded as TEAEs.
Time frame: From the first dose date of any study drug until the end of study or cutoff date, whichever occurred earlier (median [min, max] time on treatment was 43.14 [4.4, 73.4] weeks for the KRd group and 28.79 [0.3, 107.3] weeks for the Kd group)
Population: Measured in the safety analysis set, which included all enrolled participants who received at least one dose of the investigational product(s).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Carfilzomib, Lenalidomide and Dexamethasone (KRd) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | 46 Participants |
| Carfilzomib and Dexamethasone (Kd) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | 43 Participants |