Multiple MyelomaPhase 2iStopMMNCT03815279
A Nationwide Phase 2 Trial of Patients With Smoldering and Active Multiple Myeloma (MM)
A Phase 2 study testing Carfilzomib, Lenalidomide and Dexamethasone in people with Multiple Myeloma and Smoldering Multiple Myeloma, run by Landspitali University Hospital at 1 site in Iceland.
Trial summary
The purpose of this study is to determine the efficacy of treating patients with intermediate risk smoldering multiple myeloma (SMM) with combinational therapy with dexamethasone and lenalidomide (Rd) and patients with high risk SMM with combinational therapy with Rd and carfilzomib. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma, Smoldering Multiple Myeloma
- What is being tested?
- Carfilzomib, Lenalidomide and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteIceland
- Study dates
- 24 Jun 2019to Jan 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Participants that are diagnosed with MM, high- or intermediate-risk SMM in the iStopMM study will be invited to participate in this study. Each patient must meet all the following inclusion criteria to be enrolled in the study:
- Age more than 18 years.
- Active MM or
- Smoldering myeloma, which is untreated, as defined by: Measurable M spike OR pathological FLC ratio AND bone marrow PC% > 10%
- The following laboratory values obtained ≤ 30 days prior to registration
- Calculated creatinine clearance ≥ 30mL/min (using CKD-EPI equation)
Show all 24Show fewer
- Absolute neutrophil count (ANC) > 1000/mm3
- Platelet count > 75000/mm3
- Hemoglobin ≥ 8.0 g/dL
- Total bilirubin ≤ 1.5 x ULN
- ALT and AST ≤ 3 x ULN
- Measurable disease as defined by at least one of the following:
- Serum monoclonal protein > 1.0g/L
- > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis
- Serum immunoglobulin free light chain ≥ 10 mg/dL and abnormal serum immunoglobulin kappa to lambda free light chain ratio
- Prior therapy for the treatment of solitary plasmacytoma is permitted, but >7 days should have elapsed from the last day of radiation. NOTE: Prior therapy with clarithromycin, DHEA, anakinra, pamidronate or zoledronic acid is permitted. Any additional agents not listed must be approved by the Principal Investigator.
- ECOG performance status 0, 1 or 2
- Negative pregnancy test done ≤7 days prior to C1D1, for women of childbearing potential only.
- Willing to follow strict birth control measures as outlined in the protocol.
- Female subjects: If they are of childbearing potential, agree to one of the following:
- Practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of trial drug, AND must also adhere to the guidelines of any treatment-specific pregnancy prevention program (appendix 1), if applicable, OR Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
- Male subjects: even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following: Agree to practice effective barrier contraception during the entire trial treatment period and through 90 days after the last dose of trial drug, OR Must also adhere to the guidelines of any treatment-specific pregnancy prevention program (appendix 1), if applicable, OR Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception). Willing to return to enrolling institution for follow-up during the Active Treatment Phase of the trial. Agree not to donate sperm for at least 90 days after the last dose of carfilzomib
- Willing to provide samples for planned research
- Life expectancy > 6 months
Who cannot join
- MGUS or low-risk smoldering myeloma.
- Diagnosed or treated for another malignancy ≤ 2 years before trial enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. NOTE: Subjects with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- If any of the following exist at screening, subject will not be eligible for trial because this trial involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception (per protocol)
- Other co-morbidity which would interfere with subject's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
- Other concurrent chemotherapy, or any ancillary therapy considered investigational.
- NOTE: Bisphosphonates are considered to be supportive care rather than therapy, and are thus allowed while on protocol treatment.
Show all 16Show fewer
- Peripheral neuropathy > Grade 3 on clinical examination or grade 2 with pain within 30 days prior to C1D1.
- Major surgery ≤14 days prior to C1D1.
- Evidence of current uncontrolled cardiovascular conditions, including hypertension, cardiac arrhythmias, congestive heart failure, unstable angina, or myocardial infarction within the past 6 months. Note: Prior to trial entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.
- Known human immunodeficiency virus (HIV) positive.
- Known hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.
- Any medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
- Known allergies, hypersensitivity, or intolerance to corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure), or known sensitivity to mammalian-derived products.
- Known allergies, hypersensitivity, or intolerance to trial drugs.
- Inability to comply with protocol/procedures.
- LVEF < 40% for patients treated with carfilzomib.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM): A Nationwide Phase 2 Trial of Patients With Smoldering and Active Multiple Myeloma (MM)
The purpose of this study is to determine the efficacy of treating patients with intermediate risk smoldering multiple myeloma (SMM) with combinational therapy with dexamethasone and lenalidomide (Rd) and patients with high risk SMM with combinational therapy with Rd and carfilzomib.
Read the detailed description
This is an open label, single center, phase II study assessing the efficacy of treating patients with intermediate-risk smoldering myeloma (SMM) with combinational therapy with dexamethasone and lenalidomide and treating patients with high risk SMM and active multiple myeloma (MM) with combinational therapy with dexamethasone, lenalidomide and carfilzomib. Patients that are eligible for this study are participants in the IstopMM study (ClinicalTrials.gov number, NCT03327597) that are diagnosed with intermediate or high-risk SMM or active MM.
- Conditions
- Multiple Myeloma, Smoldering Multiple Myeloma
- Being tested
- Carfilzomib, Lenalidomide, Dexamethasone
- Keywords
- Multiple Myeloma, Smoldering Multiple Myeloma, Carfilzomib, Lenalidomide, Screening
- Medical subject headings
- Multiple Myeloma, Smoldering Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
Also called Kyprolis
Carfilzomib will be administered intravenously three times per cycle (28 day cycles) for cycle 1-12. Thereafter twice per cycle for cycle 13-24
LenalidomideDrug
Also called Revlimid
Lenalidomide PO once daily on days 1-21 of a 28 day cycle
DexamethasoneDrug
Also called Dexasone
Dexamethasone will be administered weekly
| Study group | Role | What they receive |
|---|---|---|
| High-risk SMM and MM | Experimental | Twelve cycles of Carfilzomib-Lenalidomide-Dexamethason. Each cycle is 28 days. Carfilzomib intravenous, days 1, 8 and 15 (starting dose, 20 mg/m2 on day 1 of cycle 1; target dose, 56 mg/m2 thereafter) during cycles 1 through 12.
Lenalidomide 25 mg orally once a day (3 weeks on/one week off) for 52 weeks. Dexamethasone 40 mg weekly for 16 weeks then 20 mg weekly for 16 weeks and thereafter 10 mg weekly for 16 weeks.
Maintenance (1 year):
Carfilzomib intravenous days 1 and 15 (56 mg/m2) during cycles 13 through 24. Lenalidomide 10 mg orally once a day (3 weeks on/one week off) for 52 weeks Dexamethasone 10 mg weekly for 52 weeks. Receives: Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone |
| Intermediate-risk SMM | Experimental | Lenalidomide 25 mg orally once a day (3 weeks on/one week off) for 52 weeks. Dexamethasone 40 mg weekly for 16 weeks, then 20 mg weekly for 16 weeks.
Maintenance (1 year):
Lenalidomide 10 mg orally once a day (3 weeks on/one week off) for 52 weeks. Receives: Drug: Lenalidomide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of MRD negativity
Minimal residual disease (MRD) as determined VDJ sequencing
Measured: 36 months after study enrollment
Secondary outcomes (2)
Progression free survival
Rates of progression free survival with progression being determined by IMWG response criteria
Measured: Up until 3 years after treatment
Overall survival
Overall survival as determened by the Icelandic National Cause of Death Registry
Measured: Up until 3 years after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2019
- Study start24 Jun 2019
- Primary completionJan 2024 (estimated)
- Study completionJan 2028 (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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- An investigator initiated, academic, non-randomized, open-label phase 2 study that will assess carfilzomib, lenalidomide and dexamethasone regimen as treatment in patients with intermediate-risk (not carfilzomib) or high-risk SMM or active MM.
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Landspitali University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen, Celgene, University of Iceland, Memorial Sloan Kettering Cancer Center
- Responsible party
- Sponsor
- Investigators
- Sigurdur Y Kristinsson, MD, PhD, Principal investigator, Landspitali University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03815279
- Sponsor's protocol ID
- LSH-17-001
- Acronym
- iStopMM
- Status last verified
- Aug 2019
- First submitted
- 9 Jan 2019
- Last updated
- 16 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Iceland Screens Treats or Prevents Multiple Myeloma (iStopMM): A Nationwide Phase 2 Trial of Patients With Smoldering and Active Multiple Myeloma (MM)
- ClinicalTrials.gov ID
- NCT03815279
- Acronym / sponsor ID
- iStopMM / LSH-17-001
- Conditions
- Multiple Myeloma, Smoldering Multiple Myeloma
- Keywords
- Multiple Myeloma, Smoldering Multiple Myeloma, Carfilzomib, Lenalidomide, Screening
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Landspitali University HospitalUniversity, hospital or other
- Collaborators
- Amgen, Celgene, University of Iceland, Memorial Sloan Kettering Cancer Center
- Study start
- 24 Jun 2019 (actual)
- Primary completion
- Jan 2024 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 24 Jan 2019 (actual)
- 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.
The purpose of this study is to determine the efficacy of treating patients with intermediate risk smoldering multiple myeloma (SMM) with combinational therapy with dexamethasone and lenalidomide (Rd) and patients with high risk SMM with combinational therapy with Rd and carfilzomib.
Detailed description
This is an open label, single center, phase II study assessing the efficacy of treating patients with intermediate-risk smoldering myeloma (SMM) with combinational therapy with dexamethasone and lenalidomide and treating patients with high risk SMM and active multiple myeloma (MM) with combinational therapy with dexamethasone, lenalidomide and carfilzomib. Patients that are eligible for this study are participants in the IstopMM study (ClinicalTrials.gov number, NCT03327597) that are diagnosed with intermediate or high-risk SMM or active MM.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- An investigator initiated, academic, non-randomized, open-label phase 2 study that will assess carfilzomib, lenalidomide and dexamethasone regimen as treatment in patients with intermediate-risk (not carfilzomib) or high-risk SMM or active MM.
| Arm | Type | Receives |
|---|---|---|
| High-risk SMM and MM | Experimental | Drug: Carfilzomib, Drug: Lenalidomide, Drug: DexamethasoneTwelve cycles of Carfilzomib-Lenalidomide-Dexamethason. Each cycle is 28 days. Carfilzomib intravenous, days 1, 8 and 15 (starting dose, 20 mg/m2 on day 1 of cycle 1; target dose, 56 mg/m2 thereafter) during cycles 1 through 12. Lenalidomide 25 mg orally once a day (3 weeks on/one week off) for 52 weeks. Dexamethasone 40 mg weekly for 16 weeks then 20 mg weekly for 16 weeks and thereafter 10 mg weekly for 16 weeks. Maintenance (1 year): Carfilzomib intravenous days 1 and 15 (56 mg/m2) during cycles 13 through 24. Lenalidomide 10 mg orally once a day (3 weeks on/one week off) for 52 weeks Dexamethasone 10 mg weekly for 52 weeks. |
| Intermediate-risk SMM | Experimental | Drug: Lenalidomide, Drug: DexamethasoneLenalidomide 25 mg orally once a day (3 weeks on/one week off) for 52 weeks. Dexamethasone 40 mg weekly for 16 weeks, then 20 mg weekly for 16 weeks. Maintenance (1 year): Lenalidomide 10 mg orally once a day (3 weeks on/one week off) for 52 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Participants that are diagnosed with MM, high- or intermediate-risk SMM in the iStopMM study will be invited to participate in this study. Each patient must meet all the following inclusion criteria to be enrolled in the study:
- Age more than 18 years.
- Active MM or
- Smoldering myeloma, which is untreated, as defined by: Measurable M spike OR pathological FLC ratio AND bone marrow PC% > 10%
- The following laboratory values obtained ≤ 30 days prior to registration
Key exclusion criteria (16 listed)
- MGUS or low-risk smoldering myeloma.
- Diagnosed or treated for another malignancy ≤ 2 years before trial enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. NOTE: Subjects with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- If any of the following exist at screening, subject will not be eligible for trial because this trial involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception (per protocol)
- Other co-morbidity which would interfere with subject's ability to participate in trial, e.g. uncontrolled infection, uncompensated heart or lung disease
- Other concurrent chemotherapy, or any ancillary therapy considered investigational.
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 |
|---|---|---|
| CarfilzomibAlso: KyprolisCarfilzomib will be administered intravenously three times per cycle (28 day cycles) for cycle 1-12. Thereafter twice per cycle for cycle 13-24 | Drug | High-risk SMM and MM |
| LenalidomideAlso: RevlimidLenalidomide PO once daily on days 1-21 of a 28 day cycle | Drug | High-risk SMM and MM, Intermediate-risk SMM |
| DexamethasoneAlso: DexasoneDexamethasone will be administered weekly | Drug | High-risk SMM and MM, Intermediate-risk SMM |
Primary outcome
Rate of MRD negativity
Time frame: 36 months after study enrollment
Minimal residual disease (MRD) as determined VDJ sequencing
2 secondary outcomes
Progression free survival
Time frame: Up until 3 years after treatment
Overall survival
Time frame: Up until 3 years after treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2019.
- Individual participant dataSharing planned: No
Related trials for Multiple Myeloma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
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.
Sigurdur Y Kristinsson, MD, PhD principal investigator
Landspitali University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carfilzomib, Lenalidomide and Dexamethasone in people with Multiple Myeloma and Smoldering Multiple Myeloma, run by Landspitali University Hospital at 1 site in Iceland.
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 24 inclusion and 16 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: enrolling by invitation, as of the sponsor's last update on 16 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Iceland. 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. 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?
This study is still under way. Results are not available in the source record yet.
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?
Rate of MRD negativity (time frame: 36 months after study enrollment). 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 16 Aug 2019.