Multiple MyelomaPhase 2CARFINCT02572492
Study of Carfilzomib in Multiple Myeloma Relapsed After High-dose Melphalan With Autologous Stem Cell Support
A Phase 2 study testing Induction with CAR-CY-DEX and conditioning with carfilzomib and highdose melphalan, Carfilzomib/dexamethasone maintenance and Observation without carfilzomib/dexamethasone maintenance in people with Multiple Myeloma, run by Henrik Gregersen at 5 sites in 5 countries.
Trial summary
This study evaluates induction therapy with carfilzomib-cyclophosphamide-dexamethasone before salvage high-dose melphalan with autologous stem cell support (HDT) in multiple myeloma patients with relapse after HDT done at diagnosis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Induction with CAR-CY-DEX and conditioning with carfilzomib and highdose melphalan, Carfilzomib/dexamethasone maintenance and Observation without carfilzomib/dexamethasone maintenance
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 5 sitesin 5 countries
- Study dates
- Jan 2015to Apr 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Myeloma diagnosis according to IMWG criteria
- First treatment demanding relapse after HDT according to IMWG criteria
- More than 2.0 x 10m CD34+ stem cells / kg body weight in the freezer for stem cell support
- Signed informed consent given prior to any study related activities have been performed
- Age > 18 years
Who cannot join
- Demographic
- Allogeneic transplantation scheduled as a part of the treatment
- Treatment demanding relapse less than one year after HDT
- Myeloma treatment after the first HDT, except radiotherapy, bisphosphonates, denosumab and corticosteroids less than 6 days for symptom control
- Patients not having received HDT as first line treatment
- Previous treatment with carfilzomib
Show all 32Show fewer
- Expected survival of less than six months
- Performance status (WHO) ≥ 3
- Laboratory
- Serum M-component < 5 g/l and urine M-component < 200 mg/l
- Any of the following laboratory abnormalities:
- Absolute neutrophil count (ANC) < 1.0 × 109/L
- Hemoglobin < 5 mmol/L (<80 g/L) (prior RBC transfusion or recombinant human erythropoietin use is permitted)
- Platelet count < 50 × 109/L (< 30 × 109/L if myeloma involvement in the bone marrow is > 50%)
- Serum ALT or AST > 3.5 times the upper limit of normal and serum direct bilirubin > 34 µmol/L (2 mg/dL)
- Creatinine clearance (CrCl) < 15 mL/minute, either measured or calculated using a standard formula
- Concurrent conditions
- Concurrent disease making treatment with carfilzomib, cyclophosphamide or dexamethasone unsuitable
- Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to enrolment
- Major surgery within 21 days prior to enrolment
- Acute active infection requiring treatment
- Known or suspected hypersensitivity or intolerance to melphalan, dexamethasone or Captisol® (a cyclodextrin derivative)
- Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, NYHA Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, uncontrolled severe arrhythmias, or cardiac amyloidosis
- LVEF <40%, determined by 2-D transthoracic echocardiogram (ECHO) or Multigated Acquisition Scan (MUGA)
- Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrolment
- Serious hepatic disorder, including active hepatitis B or C infection
- Other serious medical or psychiatric illness likely to interfere with participation in this clinical study
- Use of any investigational agents or experimental medical device within 28 days prior to enrolment into the study
- Ethical/other
- Pregnant or lactating females
- Females of childbearing potential must agree to ongoing pregnancy testing and to practice contraception
- Male subjects must agree to practice contraception
Trial locations and contacts
5 sites in 5 countries.
5 sites in 5 countries
About this study
Official title: Phase II Study of Carfilzomib-cyclophosphamide-dexamethasone and High-dose Melphalan (HDT) Followed by Randomization Between Observation or Maintenance With Carfilzomib and Dexamethasone in Patients With Relapsed Multiple Myeloma After HDT
This study evaluates induction therapy with carfilzomib-cyclophosphamide-dexamethasone before salvage high-dose melphalan with autologous stem cell support (HDT) in multiple myeloma patients with relapse after HDT done at diagnosis. In addition, the study evaluates the effect of maintenance therapy after salvage HDT in multiple myeloma. After salvage HDT half of the patients receive maintenance therapy with carfilzomib/dexamethasone while the other half are observed without maintenance therapy.
Read the detailed description
The survival in younger myeloma patients improved in the nineties with the introduction of high-dose melphalan with autologous stem cell support (HDT) and despite the emergence of novel therapies HDT remains a keystone in myeloma treatment. However, all patients will eventually experience relapse after HDT performed at diagnosis. Eligible patients with late relapse are considered for salvage HDT. The duration of response after salvage HDT is in most studies reported to be approximately half the length of the response after initial HDT. The choice of induction treatment before HDT might affect the outcome after the induction therapy as well as the outcome after the HDT. In other settings the novel proteasome inhibitor Carfilzomib has showed superiority to the first-in-class proteasome inhibitor bortezomib. In addition, carfilzomib has a favourable profile of side effects. Thus, the aim of this phase 2 study is to evaluate induction therapy with carfilzomib-cyclophosphamide-dexamethasone before salvage HDT. The primary end-point in this part of the study is comparison of time to progression after the initial HDT and time to progression after salvage HDT when four series of carfilzomib-cyclophosphamide-dexamethasone are used as induction therapy. In the study Carfilzomib is also included in the conditioning regimen with administration of Iv carfilzomib 27 mg/sqm on day -2 and -1. The standard conditioning regime consists of Iv melphalan 200 mg/sqm on day -2 and reinfusion of at least 2.0 x 10m CD34+ stem cells/kg body weight on day 0.
The purpose of maintenance therapy in multiple myeloma is to prolong the time to progression of disease. There are limited data on the impact of maintenance therapy after salvage HDT. Another important aim of the study is therefore to evaluate the effect of carfilzomib/dexamethasone given every other week compared to observation without maintenance therapy. This part of the study starts two months after HDT. The randomization is stratified according to relapse 1 - 2 years or > 2 years after HDT, ISS stage and standard versus high-risk cytogenetics. The primary end-point of this part of the study is comparison of time to progression in carfilzomib-dexamethasone maintenance arm and in the observational arm. Patients will continue on maintenance therapy/observation until progression, end of study or fulfil standard criteria for discontinuation of treatment according to the protocol.
The study will include 200 patients with relapse of multiple myeloma more than one year after initial HDT. It is a prerequisite that the patients have at least 2.0 x 10m CD34+ stem cells/kg body weight saved in the freezer. The study is conducted by the Nordic Myeloma Study Group (NMSG) at clinics in Denmark, Sweden, Norway, Finland and Lithuania. The first patient was included in January 2015 and enrolment is expected to continue until December 2017. The study ends when the last included patient has been followed for 9 months after randomization.
- Conditions
- Multiple Myeloma
- Being tested
- Induction with CAR-CY-DEX and conditioning with carfilzomib and highdose melphalan, Carfilzomib/dexamethasone maintenance, Observation without carfilzomib/dexamethasone maintenance
- Keywords
- Multiple Myeloma, Recurrence, Carfilzomib, Salvage Therapy, Transplantation, Autologous
- Medical subject headings
- Multiple Myeloma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Induction with CAR-CY-DEX and conditioning with carfilzomib and highdose melphalanDrug
Also called Kyprolis
All patients entering the study receive four series of CAR-CY-DEX (Cycle 1 with iv carfilzomib 20 mg/sqm on days 1 and 2, and iv carfilzomib 36 mg/sqm on days 8, 9, 15 and 16. Cycle 2 - 4 with iv carfilzomib 36 mg/sqm on days 1, 2, 8, 9, 15 and 16. P.o. cyclophosphamide 300 mg/sqm on days 1, 8 and 15 and p.o. dexamethasone 20 mg on days 1, 2, 8, 9, 15 and 16 in each 28-days series)
Subsequently all patients receive the conditioning regimen:
Iv carfilzomib 27 mg/sqm on day -2 and -1 Iv melphalan 200 mg/sqm on day -2 > 2.0 m CD34+ stem cells/kg body weight on day 0
Carfilzomib/dexamethasone maintenanceDrug
Also called Kyprolis
Maintenance therapy two months after salvage HDT with iv carfilzomib 27 mg/sqm every second week and p.o. dexamethasone 20 mg every second week. The maintenance dose of carfilzomib will be escalated to 56 mg/sqm after 4 weeks provided acceptable side effects.
Observation without carfilzomib/dexamethasone maintenanceDrug
Observation without carfilzomib/dexamethasone maintenance
| Study group | Role | What they receive |
|---|---|---|
| Carfilzomib/dexamethasone maintenance | Experimental | Carfilzomib/dexamethasone maintenance after salvage HDT Receives: Drug: Induction with CAR-CY-DEX and conditioning with carfilzomib and highdose melphalan; Drug: Carfilzomib/dexamethasone maintenance |
| Observation without maintenance | Sham comparator | Observation without maintenance after salvage HDT Receives: Drug: Induction with CAR-CY-DEX and conditioning with carfilzomib and highdose melphalan; Drug: Observation without carfilzomib/dexamethasone maintenance |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of time to progression after high-dose melphalan with stem cell support (HDT) performed at diagnosis and time to progression after a salvage HDT combined with carfilzomib-cyclophosphamide-dexamethasone
Measured: 3 years
Comparison of time to progression between carfilzomib-dexamethasone maintenance and observation in patients treated with salvage HDT.
Measured: 3 years
Secondary outcomes (6)
Adverse events assessed by CTCAE v4.0 in carfilzomib-cyclophosphamide-dexamethasone induction regime and carfilzomib as part of the high-dose melphalan conditioning
Measured: 5 months
Response rates of carfilzomib-cyclophosphamide-dexamethasone induction therapy and HDT
Measured: 5 months
Time to marrow regeneration (neutrophil- and platelet recovery) after the HDT
Measured: 3 weeks
Adverse events assessed by CTCAE v4.0 in maintenance treatment with carfilzomib-dexamethasone
Measured: 3 years
Comparison of overall survival between carfilzomib-dexamethasone maintenance and observation in patients treated with a salvage HDT
Measured: 3 years
Quality of life assessed by EORTC QLQ-MY20 and EORTC QLQ-C30
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2015 (estimated)
- Study startJan 2015
- Primary completion23 Apr 2018
- Study completionApr 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Henrik Gregersen
- Sponsor type
- University, hospital or other
- Collaborators
- Nordic Myeloma Study Group
- Responsible party
- Sponsor-investigator, Henrik Gregersen, Aalborg University Hospital
- Investigators
- Henrik Gregersen, MD, Principal investigator, Aalborg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02572492
- Sponsor's protocol ID
- NMSG#20/13
- Other IDs
- 2013-003789-15
- Acronym
- CARFI
- Status last verified
- Aug 2018
- First submitted
- 6 Oct 2015
- Last updated
- 17 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Carfilzomib-cyclophosphamide-dexamethasone and High-dose Melphalan (HDT) Followed by Randomization Between Observation or Maintenance With Carfilzomib and Dexamethasone in Patients With Relapsed Multiple Myeloma After HDT
- ClinicalTrials.gov ID
- NCT02572492
- Acronym / sponsor ID
- CARFI / NMSG#20/13
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Recurrence, Carfilzomib, Salvage Therapy, Transplantation, Autologous
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Henrik GregersenUniversity, hospital or other
- Collaborators
- Nordic Myeloma Study Group
- Study start
- Jan 2015
- Primary completion
- 23 Apr 2018 (actual)
- Study completion
- Apr 2019 (estimated)
- First posted
- 9 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates induction therapy with carfilzomib-cyclophosphamide-dexamethasone before salvage high-dose melphalan with autologous stem cell support (HDT) in multiple myeloma patients with relapse after HDT done at diagnosis. In addition, the study evaluates the effect of maintenance therapy after salvage HDT in multiple myeloma. After salvage HDT half of the patients receive maintenance therapy with carfilzomib/dexamethasone while the other half are observed without maintenance therapy.
Detailed description
The survival in younger myeloma patients improved in the nineties with the introduction of high-dose melphalan with autologous stem cell support (HDT) and despite the emergence of novel therapies HDT remains a keystone in myeloma treatment. However, all patients will eventually experience relapse after HDT performed at diagnosis. Eligible patients with late relapse are considered for salvage HDT. The duration of response after salvage HDT is in most studies reported to be approximately half the length of the response after initial HDT. The choice of induction treatment before HDT might affect the outcome after the induction therapy as well as the outcome after the HDT. In other settings the novel proteasome inhibitor Carfilzomib has showed superiority to the first-in-class proteasome inhibitor bortezomib. In addition, carfilzomib has a favourable profile of side effects. Thus, the aim of this phase 2 study is to evaluate induction therapy with carfilzomib-cyclophosphamide-dexamethasone before salvage HDT. The primary end-point in this part of the study is comparison of time to progression after the initial HDT and time to progression after salvage HDT when four series of carfilzomib-cyclophosphamide-dexamethasone are used as induction therapy. In the study Carfilzomib is also included in the conditioning regimen with administration of Iv carfilzomib 27 mg/sqm on day -2 and -1. The standard conditioning regime consists of Iv melphalan 200 mg/sqm on day -2 and reinfusion of at least 2.0 x 10m CD34+ stem cells/kg body weight on day 0.
The purpose of maintenance therapy in multiple myeloma is to prolong the time to progression of disease. There are limited data on the impact of maintenance therapy after salvage HDT. Another important aim of the study is therefore to evaluate the effect of carfilzomib/dexamethasone given every other week compared to observation without maintenance therapy. This part of the study starts two months after HDT. The randomization is stratified according to relapse 1 - 2 years or > 2 years after HDT, ISS stage and standard versus high-risk cytogenetics. The primary end-point of this part of the study is comparison of time to progression in carfilzomib-dexamethasone maintenance arm and in the observational arm. Patients will continue on maintenance therapy/observation until progression, end of study or fulfil standard criteria for discontinuation of treatment according to the protocol.
The study will include 200 patients with relapse of multiple myeloma more than one year after initial HDT. It is a prerequisite that the patients have at least 2.0 x 10m CD34+ stem cells/kg body weight saved in the freezer. The study is conducted by the Nordic Myeloma Study Group (NMSG) at clinics in Denmark, Sweden, Norway, Finland and Lithuania. The first patient was included in January 2015 and enrolment is expected to continue until December 2017. The study ends when the last included patient has been followed for 9 months after randomization.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Carfilzomib/dexamethasone maintenance | Experimental | Drug: Induction with CAR-CY-DEX and conditioning with carfilzomib and highdose melphalan, Drug: Carfilzomib/dexamethasone maintenanceCarfilzomib/dexamethasone maintenance after salvage HDT |
| Observation without maintenance | Sham comparator | Drug: Induction with CAR-CY-DEX and conditioning with carfilzomib and highdose melphalan, Drug: Observation without carfilzomib/dexamethasone maintenanceObservation without maintenance after salvage HDT |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Myeloma diagnosis according to IMWG criteria
- First treatment demanding relapse after HDT according to IMWG criteria
- More than 2.0 x 10m CD34+ stem cells / kg body weight in the freezer for stem cell support
- Signed informed consent given prior to any study related activities have been performed
- Age > 18 years
Key exclusion criteria (32 listed)
- Demographic
- Allogeneic transplantation scheduled as a part of the treatment
- Treatment demanding relapse less than one year after HDT
- Myeloma treatment after the first HDT, except radiotherapy, bisphosphonates, denosumab and corticosteroids less than 6 days for symptom control
- Patients not having received HDT as first line treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Induction with CAR-CY-DEX and conditioning with carfilzomib and highdose melphalanAlso: KyprolisAll patients entering the study receive four series of CAR-CY-DEX (Cycle 1 with iv carfilzomib 20 mg/sqm on days 1 and 2, and iv carfilzomib 36 mg/sqm on days 8, 9, 15 and 16. Cycle 2 - 4 with iv carfilzomib 36 mg/sqm on days 1, 2, 8, 9, 15 and 16. P.o. cyclophosphamide 300 mg/sqm on days 1, 8 and 15 and p.o. dexamethasone 20 mg on days 1, 2, 8, 9, 15 and 16 in each 28-days series) Subsequently all patients receive the conditioning regimen: Iv carfilzomib 27 mg/sqm on day -2 and -1 Iv melphalan 200 mg/sqm on day -2 > 2.0 m CD34+ stem cells/kg body weight on day 0 | Drug | Carfilzomib/dexamethasone maintenance, Observation without maintenance |
| Carfilzomib/dexamethasone maintenanceAlso: KyprolisMaintenance therapy two months after salvage HDT with iv carfilzomib 27 mg/sqm every second week and p.o. dexamethasone 20 mg every second week. The maintenance dose of carfilzomib will be escalated to 56 mg/sqm after 4 weeks provided acceptable side effects. | Drug | Carfilzomib/dexamethasone maintenance |
| Observation without carfilzomib/dexamethasone maintenanceObservation without carfilzomib/dexamethasone maintenance | Drug | Observation without maintenance |
Primary outcome
Comparison of time to progression after high-dose melphalan with stem cell support (HDT) performed at diagnosis and time to progression after a salvage HDT combined with carfilzomib-cyclophosphamide-dexamethasone
Time frame: 3 years
Comparison of time to progression between carfilzomib-dexamethasone maintenance and observation in patients treated with salvage HDT.
Time frame: 3 years
6 secondary outcomes
Adverse events assessed by CTCAE v4.0 in carfilzomib-cyclophosphamide-dexamethasone induction regime and carfilzomib as part of the high-dose melphalan conditioning
Time frame: 5 months
Response rates of carfilzomib-cyclophosphamide-dexamethasone induction therapy and HDT
Time frame: 5 months
Time to marrow regeneration (neutrophil- and platelet recovery) after the HDT
Time frame: 3 weeks
Adverse events assessed by CTCAE v4.0 in maintenance treatment with carfilzomib-dexamethasone
Time frame: 3 years
Comparison of overall survival between carfilzomib-dexamethasone maintenance and observation in patients treated with a salvage HDT
Time frame: 3 years
Quality of life assessed by EORTC QLQ-MY20 and EORTC QLQ-C30
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henrik Gregersen, MD principal investigator
Aalborg University Hospital
5 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Induction with CAR-CY-DEX and conditioning with carfilzomib and highdose melphalan, Carfilzomib/dexamethasone maintenance and Observation without carfilzomib/dexamethasone maintenance in people with Multiple Myeloma, run by Henrik Gregersen at 5 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Denmark, Finland, Lithuania, Norway, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of time to progression after high-dose melphalan with stem cell support (HDT) performed at diagnosis and time to progression after a salvage HDT combined with carfilzomib-cyclophosphamide-dexamethasone (time frame: 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2018.