High Risk Smoldering Multiple MyelomaPhase 2NCT02943473
Study on the Effect of Ibrutinib on High Risk Smoldering Multiple Myeloma Patients
A Phase 2 study testing Ibrutinib in people with High Risk Smoldering Multiple Myeloma, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
The purpose of this research study is to test whether the drug ibrutinib (trademark name: IMBRUVICA®) is effective at preventing the development of multiple myeloma in people who currently have smoldering myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High Risk Smoldering Multiple Myeloma
- What is being tested?
- Ibrutinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 18 May 2017to 10 Sep 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- High risk SMM, defined as follows by Mayo Clinic criteria:
- Bone marrow plasma cells between 10% and 60%
- Serum M-protein ≥ 3 g/dL [except IgA ≥ 2 g/dL] or urine M-protein > 500 mg per 24 hours
- Serum free light chain ratio < 0.126 or > 8; an involved to uninvolved ratio of ≥ 100 is permitted
- Measurable disease, defined as: M-protein ≥ 1 g/dL OR Bence-Jones protein (BJP) > 200 mg/24 hr OR involved free light chain > 100 mg/dL
- Diagnosed with SMM within the last 4 years
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- Laboratory
- Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening, with the exception of pegylated G-CSF (pegfilgrastim) and darbopoetin which require at least 14 days prior to screening defined as:
- Absolute neutrophil count > 750 cells/mm3 (1.0 x 109/L).
- Platelet count > 75,000 cells/mm3 (75 x 109/L).
- Adequate hepatic and renal function defined as:
- Serum aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN).
- Estimated creatinine clearance ≥ 30 ml/min (Cockcroft-Gault)
- Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin, in which case the total bilirubin should be < 3 x ULN)
- PT/INR < 1.5 x ULN and PTT (aPTT) < 1.5 x ULN
- Demographic
- Men and women ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status of < 2
Who cannot join
- No end organ damage attributable to a plasma cell disorder, defined as having ANY of the following:
- Hypercalcemia: Serum calcium > 1 mg/dL above the upper limit of normal or > 11 mg/dL
- Renal insufficiency: Serum creatinine > 2 mg/dL or creatinine clearance < 30 mL per min
- Anemia: Hemoglobin value > 2 g/dL below the upper limit of normal or a hemoglobin value < 10 g/dL
- Bone lesions: One or more lytic lesions on skeletal radiography, CT, MRI, PET-CT, or PET-MRI
- Bone marrow plasma cells < 10% or > 60%
Show all 24Show fewer
- Has received prior anti-myeloma therapy of any type
- Has received prior bisphosphonate therapy
- Has received an investigational drug, investigational vaccine, or has used an investigational medical device within 4 weeks or 4 half-lives, whichever is longer, before Cycle 1, Day 1 of study therapy
- Osteoporosis, defined as having a T-score on DEXA of ≤ -2.5
- Concurrent Conditions
- History of other malignancies, except:
- Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- Adequately treated carcinoma in situ without evidence of disease
- Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc). Any use of corticosteroids EITHER for > 14 days OR at dosages > 20 mg/day of prednisone or equivalent is prohibited.
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
- Recent infection requiring systemic treatment that was completed ≤ 14 days before the first dose of study drug
- Known bleeding disorders (eg, von Willebrand's disease) or hemophilia
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment
- Known HIV, HCV or HBV infection. Subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
- Any uncontrolled active systemic infection
- Major surgery within 4 weeks of first dose of study drug
- Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigators' opinion, could compromise the subject's safety or put the study outcomes at undue risk
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: A Phase 2 Study of the Effect of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib on Disease Response in Patients With High Risk Smoldering Multiple Myeloma
The purpose of this research study is to test whether the drug ibrutinib (trademark name: IMBRUVICA®) is effective at preventing the development of multiple myeloma in people who currently have smoldering myeloma. The researchers conducting this trial) have reason to believe that ibrutinib can delay the development of multiple myeloma, thus giving people who currently have smoldering myeloma a longer period of time when they feel healthy and well.
Smoldering myeloma is an abnormal condition that is considered to be an early phase of the disease multiple myeloma. In this disorder, there is an abnormal growth of plasma cells, which is a type of blood cell found in the bone marrow. This growth is not as severe in people with smoldering myeloma as it is in multiple myeloma, so people with smoldering myeloma do not have any symptoms and tend to feel well. However, they have a higher risk of developing multiple myeloma than people in the general population.
Read more
Some people with smoldering myeloma are at an especially high risk of developing myeloma - 50% of these people will develop multiple myeloma 2 years after they are diagnosed with smoldering myeloma. The investigators identify these people by looking at the amount of myeloma in the bone marrow (called "bone marrow plasma cell percentage") and the amount of myeloma protein (called "serum protein electrophoresis" and "serum free light chain assay") in the blood. To be considered high risk, individuals must have highly abnormal levels for these tests.
Based upon current guidelines, people with smoldering myeloma do not require any treatment. However, known is that many of these people will develop multiple myeloma in the near future. Currently there have been no proven and effective way of preventing these people from developing multiple myeloma, which remains an incurable disease.
Read the detailed description
This is a phase 2, open-label, single center, prospective pilot study designed to assess the efficacy of ibrutinib in subjects with high risk smoldering multiple myeloma.
All enrolled subjects will be treated with ibrutinib 560 mg (4 capsules, each containing 140 mg) taken PO daily for 12 cycles (28 days each). If a subject demonstrates benefit from ibrutinib, therapy may be extended beyond 12 cycles to a maximum of 2 years. Subjects who progress and meet criteria for symptomatic multiple myeloma will be withdrawn from study.
An initial cohort of 15 subjects will be accrued. If 4 or more patients progress to symptomatic myeloma in one year, then the study will be reviewed with the FDA to determine whether to employ a higher dose of ibrutinib, or to stop for futility. Otherwise, 21 additional patients will be accrued for a total sample size of 36.
- Conditions
- High Risk Smoldering Multiple Myeloma
- Being tested
- Ibrutinib
- Keywords
- Smoldering multiple myeloma, myeloma, smoldering, ibrutinib
- Medical subject headings
- Smoldering Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called IMBRUVICA
Ibrutinib is a type of drug called a "kinase inhibitor." Kinases are proteins inside cells that help cells live and grow. Ibrutinib blocks a specific kinase protein in our bodies. This protein is thought to be very important in helping blood cancer cells live and grow. By blocking this kinase protein, ibrutinib stops cancer cells from growing.
| Study group | Role | What they receive |
|---|---|---|
| Ibrutinib | Experimental | Ibrutinib (trademark name is IMBRUVICA®). 560 mg dose administered on a continuous basis Receives: Drug: Ibrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Without Symptomatic Myeloma
Disease response - the proportion of patients with high risk smoldering multiple myeloma who do not progress to symptomatic myeloma as defined by the IMWG.
Measured: up to 1 year
Secondary outcomes (10)
Overall Response Rate
Overall response rate, defined as partial response or better per IMWG criteria. (IMWG response criteria are - Complete Response, Very good partial response, partial response, Minimal response, stable disease, and progressive disease)
Measured: up to 1 year
Bone Density Changes
Changes in bone density, particularly in patients with osteopenia (defined as T-score on bone densitometry testing (DEXA) of -1 to -2.5).
Measured: baseline and one year
PET-MRI Changes
Changes in PET-MRI, particularly in patients with osteopenia
Measured: baseline and one year
Change in Serum Interleukin-6 (IL-6)
Bone Related Biomarker Changes
Measured: baseline and up to one year
Change in Serum Stromal Cell-derived Factor-1 (SDF-1)
Bone Related Biomarker Changes
Measured: baseline and up to one year
Change in Serum Receptor Activator of Nuclear-factor Kappa B Ligand (RANKL)
Bone Related Biomarker Changes
Measured: baseline and up to one year
Change in Serum Macrophage Inflammatory Protein-1α (MIP-1α)
Bone Related Biomarker Changes
Measured: baseline and up to one year
Change in Serum Dickkopf-1 (DKK-1)
Bone Related Biomarker Changes
Measured: baseline and up to one year
Change in Serum C-terminal Telopeptide (CTX)
Bone Related Biomarker Changes
Measured: baseline and up to one year
Change in Urine N-terminal Telopeptide (NTx)
Bone Related Biomarker Changes
Measured: baseline and up to one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2016 (estimated)
- Study start18 May 2017
- Primary completion10 Sep 2019
- Study completion10 Sep 2019
Why it stopped: Poor accrual and risk/benefit ratio.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for High Risk Smoldering Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- Pharmacyclics LLC.
- Responsible party
- Principal investigator, Ajai Chari, Icahn School of Medicine at Mount Sinai
- Investigators
- Ajai Chari, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02943473
- Sponsor's protocol ID
- GCO 16-1867
- Status last verified
- Nov 2020
- First submitted
- 21 Oct 2016
- Last updated
- 16 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of the Effect of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib on Disease Response in Patients With High Risk Smoldering Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02943473
- Acronym / sponsor ID
- GCO 16-1867
- Conditions
- High Risk Smoldering Multiple Myeloma
- Keywords
- Smoldering multiple myeloma, myeloma, smoldering, ibrutinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor accrual and risk/benefit ratio.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- Pharmacyclics LLC.
- Study start
- 18 May 2017 (actual)
- Primary completion
- 10 Sep 2019 (actual)
- Study completion
- 10 Sep 2019 (actual)
- First posted
- 24 Oct 2016 (estimated)
- Results
- Posted 16 Dec 2020
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 research study is to test whether the drug ibrutinib (trademark name: IMBRUVICA®) is effective at preventing the development of multiple myeloma in people who currently have smoldering myeloma. The researchers conducting this trial) have reason to believe that ibrutinib can delay the development of multiple myeloma, thus giving people who currently have smoldering myeloma a longer period of time when they feel healthy and well.
Smoldering myeloma is an abnormal condition that is considered to be an early phase of the disease multiple myeloma. In this disorder, there is an abnormal growth of plasma cells, which is a type of blood cell found in the bone marrow. This growth is not as severe in people with smoldering myeloma as it is in multiple myeloma, so people with smoldering myeloma do not have any symptoms and tend to feel well. However, they have a higher risk of developing multiple myeloma than people in the general population.
Some people with smoldering myeloma are at an especially high risk of developing myeloma - 50% of these people will develop multiple myeloma 2 years after they are diagnosed with smoldering myeloma. The investigators identify these people by looking at the amount of myeloma in the bone marrow (called "bone marrow plasma cell percentage") and the amount of myeloma protein (called "serum protein electrophoresis" and "serum free light chain assay") in the blood. To be considered high risk, individuals must have highly abnormal levels for these tests.
Based upon current guidelines, people with smoldering myeloma do not require any treatment. However, known is that many of these people will develop multiple myeloma in the near future. Currently there have been no proven and effective way of preventing these people from developing multiple myeloma, which remains an incurable disease.
Detailed description
This is a phase 2, open-label, single center, prospective pilot study designed to assess the efficacy of ibrutinib in subjects with high risk smoldering multiple myeloma.
All enrolled subjects will be treated with ibrutinib 560 mg (4 capsules, each containing 140 mg) taken PO daily for 12 cycles (28 days each). If a subject demonstrates benefit from ibrutinib, therapy may be extended beyond 12 cycles to a maximum of 2 years. Subjects who progress and meet criteria for symptomatic multiple myeloma will be withdrawn from study.
An initial cohort of 15 subjects will be accrued. If 4 or more patients progress to symptomatic myeloma in one year, then the study will be reviewed with the FDA to determine whether to employ a higher dose of ibrutinib, or to stop for futility. Otherwise, 21 additional patients will be accrued for a total sample size of 36.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ibrutinib | Experimental | Drug: IbrutinibIbrutinib (trademark name is IMBRUVICA®). 560 mg dose administered on a continuous basis |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- High risk SMM, defined as follows by Mayo Clinic criteria:
- Diagnosed with SMM within the last 4 years
- Laboratory
- Adequate hematologic function independent of transfusion and growth factor support for at least 7 days prior to screening, with the exception of pegylated G-CSF (pegfilgrastim) and darbopoetin which require at least 14 days prior to screening defined as:
- Adequate hepatic and renal function defined as:
Key exclusion criteria (24 listed)
- No end organ damage attributable to a plasma cell disorder, defined as having ANY of the following:
- Bone marrow plasma cells < 10% or > 60%
- Has received prior anti-myeloma therapy of any type
- Has received prior bisphosphonate therapy
- Has received an investigational drug, investigational vaccine, or has used an investigational medical device within 4 weeks or 4 half-lives, whichever is longer, before Cycle 1, Day 1 of study therapy
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 |
|---|---|---|
| IbrutinibAlso: IMBRUVICAIbrutinib is a type of drug called a "kinase inhibitor." Kinases are proteins inside cells that help cells live and grow. Ibrutinib blocks a specific kinase protein in our bodies. This protein is thought to be very important in helping blood cancer cells live and grow. By blocking this kinase protein, ibrutinib stops cancer cells from growing. | Drug | Ibrutinib |
Primary outcome
Number of Patients Without Symptomatic Myeloma
Time frame: up to 1 year
Disease response - the proportion of patients with high risk smoldering multiple myeloma who do not progress to symptomatic myeloma as defined by the IMWG.
10 secondary outcomes
Overall Response Rate
Time frame: up to 1 year
Bone Density Changes
Time frame: baseline and one year
PET-MRI Changes
Time frame: baseline and one year
Change in Serum Interleukin-6 (IL-6)
Time frame: baseline and up to one year
Change in Serum Stromal Cell-derived Factor-1 (SDF-1)
Time frame: baseline and up to one year
Change in Serum Receptor Activator of Nuclear-factor Kappa B Ligand (RANKL)
Time frame: baseline and up to one year
Change in Serum Macrophage Inflammatory Protein-1α (MIP-1α)
Time frame: baseline and up to one year
Change in Serum Dickkopf-1 (DKK-1)
Time frame: baseline and up to one year
Change in Serum C-terminal Telopeptide (CTX)
Time frame: baseline and up to one year
Change in Urine N-terminal Telopeptide (NTx)
Time frame: baseline and up to one year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for High Risk Smoldering Multiple Myeloma
RecruitingPhase 3
A Study to Compare Linvoseltamab and Daratumumab Treatment in High-Risk Smoldering Multiple Myeloma (HR-SMM)
High Risk Smoldering Multiple Myeloma (HR-SMM)
RecruitingPhase 2
Isatuximab and Iberdomide as Immunotherapy for High Risk in Smouldering Myeloma
Smouldering Myeloma
Active, not recruitingPhase 2
Isatuximab With or Without Lenalidomide in Patients With High Risk Smoldering Multiple Myeloma (ISAMAR)
Smoldering Plasma Cell Myeloma
Active, not recruitingPhase 3
Lenalidomide or Observation in Treating Patients With Asymptomatic High-Risk Smoldering Multiple Myeloma
Light Chain Deposition Disease, Smoldering Multiple Myeloma
RecruitingPhase 1
A Study of JNJ-79635322 in Combination With Daratumumab With or Without Lenalidomide for Multiple Myeloma, Newly Diagnosed AL Amyloidosis, and High-risk Smoldering Multiple Myeloma or JNJ-79635322 in Combination With Pomalidomide for Multiple Myeloma
Multiple Myeloma, Smoldering Multiple Myeloma
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.
Ajai Chari, MD principal investigator
Icahn School of Medicine at Mount Sinai
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 Ibrutinib in people with High Risk Smoldering Multiple Myeloma, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
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 18 inclusion and 24 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: stopped early, as of the sponsor's last update on 16 Dec 2020. 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 United States. 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?
Yes. Results are posted in the registry (first posted 16 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Patients Without Symptomatic Myeloma (time frame: up to 1 year). 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 Dec 2020.