Phase 3 Carfilzomib Study in Patients With Relapsed/Refractory Myeloma
Research type
Research Study
Full title
A Randomized, Open-label, Phase 3 Study Comparing Carfilzomib, Dexamethasone, and Daratumumab to Carfilzomib and Dexamethasone for the Treatment of Patients With Relapsed or Refractory Multiple Myeloma
IRAS ID
222219
Contact name
James Cavet
Contact email
Sponsor organisation
Amgen Ltd
Eudract number
2016-003554-33
Duration of Study in the UK
5 years, 9 months, 3 days
Research summary
Summary of Research
Multiple myeloma, a clonal neoplastic proliferation of plasma cells, is the second most common hematologic malignancy and is responsible for approximately 80000 annual\ndeaths worldwide (1% of cancer deaths). The estimated incidence of multiple myeloma\nin 2012 worldwide was 114000 persons and this represents 0.8% of all cancers.\n\nRelapsed or refractory multiple myeloma treatment has evolved rapidly in recent years.\n\nThe primary objective is to compare carfilzomib, dexamethasone, and\ndaratumumab to carfilzomib and dexamethasone in terms of progression free survival\n(PFS) in patients with multiple myeloma who have relapsed after 1 to 3 prior therapies.\n \nAmong the phase 3 studies in relapsed multiple myeloma, the results achieved with\ncarfilzomib and daratumumab based combinations suggest that these 2 agents are likely\nthe most potent in their respective classes. They both have demonstrated high rates of overall responses and significant increment of Complete response rates (CRRs).\nSubjects will receive the treatment determined by randomization for a maximum of 4 years or until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or death (whichever occurs first). All subjects will be assessed for multiple myeloma disease response according to the IMWG-URC using central laboratory test results every 28 ± 7 days. Disease response assessments will be performed every 28 ± 7 days until confirmed progressive disease (PD).\n\nThe study will be conducted at Hematology services of 124 Hospitals (4 in the UK). \nSummary of Results
This summary shows the main results from one clinical study. The results are only for this study. Other studies may find different results. Researchers and health authorities look at the results of many studies to decide which medicines work best and are safest for patients.
Amgen has committed to make research results available to the public. This summary has been provided as part of that commitment and should not be used for any other purpose. It should not be considered to make a claim for any product or to guide treatment decisions.Clinical Study Results
What does this summary cover?
Some information in this summary may be different from the approved labelling for carfilzomib (also known as Kyprolis). Your healthcare professional should refer to the full prescribing information for proper use of carfilzomib.2. Who Sponsored This Study?
Amgen Inc. One Amgen Center Drive Thousand Oaks, CA 91320-1799 USA Phone (United Kingdom): +44 1223 436441 Amgen Inc. is the sponsor of the study who made carfilzomib, one of the medicines tested in the study. Johnson & Johnson is a collaborator of Amgen for this study. Johnson & Johnson made daratumumab, one of the medicines tested in the study. Amgen would like to thank everyone who participated in this study and feels it is important to share the results of this study.3. General Information About the Clinical Study • This study took place in Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, France, Greece, Hungary, Japan, Poland, Romania, Russia, South Korea, Spain, Taiwan, Turkey, United Kingdom, and United States.
• The study began in June 2017 and ended in April 2022.
• The study was completed as planned.
Multiple myeloma is a cancer that begins in the plasma cells, which are a type of white blood cell in the bone marrow. Patients can be treated for multiple myeloma. However, multiple myeloma can come back after treatment.
Where and when was the study done?Why was the study done?
Carfilzomib is a type of treatment known as a proteasome inhibitor. Carfilzomib may prevent the breakdown of abnormal proteins in cells, causing these cells to die. Cancer cells are more sensitive to these effects than normal cells. Carfilzomib is currently approved in some countries for the treatment of adults with relapsed (the disease came back after improving with a previous treatment) or refractory (a previous treatment was not able to control the disease) multiple myeloma.
Carfilzomib is given in combination with other medicines that are approved for multiple myeloma, such as dexamethasone (a corticosteroid medicine).
Daratumumab is a type of drug called a monoclonal antibody (MAB). It works by targeting a certain protein (called CD38) on multiple myeloma cells. By doing this, daratumumab directly kills the multiple myeloma cells, and allows your immune system to destroy them. Daratumumab is currently approved in some countries for the treatment of adults with multiple myeloma.
This was a phase 3 study, the late stage of the development process of medicines for humans before they are approved for general use and after the medicines have been tested for safety and effectiveness in earlier phases. The main purpose of this study was to compare treatment with carfilzomib in combination with dexamethasone and daratumumab to treatment with carfilzomib with dexamethasone alone in patients with multiple myeloma.4. Who Was Included in This Study?
This study included 466 adults with relapsed or refractory multiple myeloma; 198 participants (42%, or about 42 out of 100) were women and 268 participants (58%, or about 58 out of 100) were men. They ranged in age from 29 to 84 years, with an average age of about 63 years.Who took part in the study?
This study took place at 102 study centers across 19 countries. The numbers of participants in each country are listed below:
• Australia: 60 participants
• Austria: 3 participants
• Belgium: 5 participants
• Bulgaria: 21 participants
• Canada: 17 participants
• Czech Republic: 28 participants
• France: 22 participants
• Greece: 43 participants
• Hungary: 16 participants
• Japan: 31 participants
• Poland: 48 participants
• Romania: 32 participants
• Russia: 36 participants
• South Korea: 24 participants
• Spain: 22 participants
• Taiwan: 8 participants
• Turkey: 27 participants
• United Kingdom: 7 participants
• United States: 16 participants
Participants were examined by a study doctor and chosen to be in the study if they met certain study requirements. Some of the key requirements included that they:
• were 18 years of age or older
• were diagnosed with multiple myeloma that came back after treatment or that no longer responded to previous treatment • had received at least 1 but no more than 3 previous treatments for multiple myeloma before entering the study • had multiple myeloma that could be accurately measured by the study doctor
55. Which Medicines Were Studied?
Participants agreed to be put into a treatment group by chance (“randomized”). This is like flipping a coin or drawing numbers out of a hat.
• 312 participants were randomized to receive carfilzomib in combination with dexamethasone and daratumumab. Participants had a 2 in 3 chance of being put into this treatment group. Four participants in this group did not receive any study treatment. The other 308 participants in this group received at least 1 dose of study treatment.
• 154 participants were randomized to receive carfilzomib and dexamethasone alone. Participants had a 1 in 3 chance of being put into this treatment group. One participant in this group did not receive any study treatment. The other 153 participants in this group received at least 1 dose of study treatment.
This was an open-label study, which means that both the participants and the study doctors knew which treatments the participants received.
Participants were checked by the study doctor about every 28 days to see if their disease was getting better or worse, or staying the same. Participants could continue to receive study treatment for up to 4 years, or until their multiple myeloma worsened, they had unacceptable side effects, they died, or they left the study for another reason.6. What Were the Side Effects?
All medicines can cause side effects, or unwanted medical problems that may happen when you take a medicine. In this study, doctors reported all the medical problems participants had. Doctors believed some of the problems could have been caused by the study medicine(s). These possible side effects are listed below.What is a side effect?
The table below shows how many participants had side effects while on study treatment and within 30 days after their last dose of study treatment. Side Effects During the Study Carfilzomib and Dexamethasone Group (153 participants) Carfilzomib, Dexamethasone, and Daratumumab Group (308 participants) How many participants had serious side effects?
34 participants (22%)
102 participants (33%) How many participants had non-serious side effects? 124 participants (81%) 260 participants (84%) How many participants died from side effects?
0 participants (0%)
5 participants (2%) How many participants stopped taking carfilzomib because of side effects? 22 participants (14%) 69 participants (22%) How many participants stopped taking dexamethasone because of side effects?
24 participants (16%)
30 participants (10%) How many participants stopped taking daratumumab because of side effects? Not applicable 18 participants (6%) If a participant had to stay in the hospital or died because of a side effect, the doctor reported that the side effect was serious.
The table below shows the serious side effects that occurred in at least 2% of participants (or about 2 out of 100).What side effects were seen?
Serious Side Effects During the Study Serious side effect Carfilzomib and Dexamethasone Group (153 participants) Carfilzomib, Dexamethasone, and Daratumumab Group (308 participants) Heart failure (when the heart does not pump blood as well as it should)
4 participants (3%)
2 participants (less than 1%) Lung infection (pneumonia) 6 participants (4%) 20 participants (7%) Fever
2 participants (1%)
8 participants (3%)
The table below shows the non-serious side effects that occurred in at least 10% of participants (or about 10 out of 100). Non-serious Side Effects During the Study Non-serious side effect Carfilzomib and Dexamethasone Group (153 participants) Carfilzomib, Dexamethasone, and Daratumumab Group (308 participants) Low number of red blood cells
26 participants (17%)
62 participants (20%) Loose stools 7 participants (5%) 54 participants (18%) Difficulty breathing
26 participants (17%)
51 participants (17%) Tiredness 20 participants (13%) 51 participants (17%) High blood pressure
40 participants (26%)
93 participants (30%) Difficulty falling and/or staying sleep 18 participants (12%) 57 participants (19%) Nausea
9 participants (6%)
39 participants (13%) Low number of neutrophils, a type of white blood cell 7 participants (5%) 36 participants (12%) Low number of blood platelets
33 participants (22%)
105 participants (34%)This section only shows the most often reported side effects considered by the study doctor as related to study medicine. No single clinical study can give a complete picture of the benefits and risks of a medicine. Information about other side effects may be available at the websites listed at the end of this summary.
7. What Were the Overall Results of the Study?
• To answer this question, the researchers looked at median progression-free survival, which is estimated as the length of time that half of the participants are expected to survive without their multiple myeloma getting worse.
• In the carfilzomib and dexamethasone treatment group, the median progression-free survival was 15.3 months.
• In the carfilzomib, dexamethasone, and daratumumab treatment group, the median progression-free survival was 27.4 months.
• These results were not likely due to chance.
• The study was completed as planned.
• More results may be available at the websites listed at the end of this summary.
How long did participants who received carfilzomib in combination with dexamethasone and daratumumab survive without their multiple myeloma getting worse, compared to participants who received carfilzomib plus dexamethasone alone?8. How Has This Study Helped Participants and Researchers?
What else is important to know about these results?
These results are only for this clinical study, which looked at a sample of 466 people with multiple myeloma. Not all participants in the study had the same results. The results for any single participant could have been better or worse than the results for their group. Other studies may find different results. These results do not predict how a study medicine may work in a single person. This research may help future participants and families by helping doctors understand more about carfilzomib in combination with other medicines used to treat multiple myeloma.9. Are There Plans for Further Studies?
If more clinical studies are done, they may be listed on public websites, such as those below. Search for the study medicine names carfilzomib (Kyprolis) and daratumumab (Darzalex) on the websites below.10. Where Can I Find More Information About This Study?
To find out more about this study, check these websites: • https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrialsregister.eu%2F&data=05%7C01%7Cgmsouth.rec%40hra.nhs.uk%7C45c27637c07d4f27e98708db941b4ac3%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638266617159121303%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=nnn9oyc62MrjB9OE%2FqP5Dh27bCm%2BOziQcnZr1XBfqnY%3D&reserved=0. Use the study identifier 2016-003554-33.
• https://gbr01.safelinks.protection.outlook.com/?url=http%3A%2F%2Fwww.clinicaltrials.gov%2F&data=05%7C01%7Cgmsouth.rec%40hra.nhs.uk%7C45c27637c07d4f27e98708db941b4ac3%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638266617159121303%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=xK%2FrE%2BG8P%2FdaY77r5YNkjTVXLW7mL1P%2FoJBZRzT8Cl0%3D&reserved=0. Use the study identifier NCT03158688.
If you participated in the study and have questions about the study results, the doctor or staff at your study center may be able to answer them.REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
17/NW/0228
Date of REC Opinion
18 May 2017
REC opinion
Further Information Favourable Opinion