Multiple MyelomaPhase 1NCT02697383
Ixazomib (MLN9708) and Dexamethasone in High Risk Smoldering Multiple Myeloma: A Clinical and Correlative Pilot Study
A Phase 1 study testing Ixazomib (MLN9708) and Dexamethasone in people with Multiple Myeloma and High Risk Smoldering Multiple Myeloma, run by Memorial Sloan Kettering Cancer Center at 6 sites in United States.
Trial summary
The purpose of this study is to see what effects, good and/or bad, the combination of ixazomib and dexamethasone has on the patient and the smoldering multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma, High Risk Smoldering Multiple Myeloma
- What is being tested?
- Ixazomib (MLN9708) and Dexamethasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 6 sitesUnited States
- Study dates
- Feb 2016to 8 May 2024
- Phase
- Phase 1
- 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
- Patients must have histologically or cytologically confirmed Smoldering Multiple Myeloma confirmed by Department of Pathology, based on the International Myeloma Working Group Criteria
- Serum M-protein ≥3 g/dl and/or bone marrow plasma cells ≥10 %,
- Absence of anemia attributed to the plasma cell disorder*: Hemoglobin >10 g/dl or not more than 2g/dL below the lower limit of normal
- Absence of renal failure attributed to the plasma cell disorder*: calculated creatinine clearance (according to Cockcroft-Gault method, MDRD, or CKD-EPI formulae) > 30 mL/min (or alternatively based on standard creatinine level criteria of 2 mg/dl)
- Absence of hypercalcemia attributed to the plasma cell disorder* (: Ca < 10.5 mg/dl or ≤ 2.5 mmol/L
- Absence of lytic bone lesion
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- Absence of Clonal bone marrow plasma cell percentage ≥60%
- Absence of Involved: uninvolved serum free light chain ratio ≥100
- Absence >1 focal lesions on MRI studies
- To be determined based on clinical and laboratory assessment by the primary oncologist
- "High-risk SMM" per Mayo Clinic or Spanish PETHEMA criteria
- Measurable disease within the past 4 weeks defined by any one of the following
- Serum monoclonal protein ≥ 1.0 g/dl
- Urine monoclonal protein >200 mg/24 hour
- Serum immunoglobulin free light chain >10 mg/dL AND abnormal kappa/lambda ratio (reference 0.26-1.65)
- Age ≥18 years
- ECOG performance status 0, 1, or 2.
- Ability to give informed consent.
- Patients must have normal organ and marrow function as defined below:
- Absolute neutrophil count ≥1.0 K/μL
- Platelets ≥ 75 K/μL (Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.)
- Hemoglobin > 10 g/dL(transfusions are not permissible)
- Total bilirubin ≤1.5 X institutional upper limit of normal AST(SGOT)/ALT(SGPT) ≤ 3.0 X institutional upper limit of normal
- Female patients who:
- Are postmenopausal for at least 24 months before the Screening visit, OR
- Are surgically sterile, OR
- If they are of childbearing potential, agree to 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 study drug, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
- Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
- Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
Who cannot join
- Participation in other clinical trials, including those with other investigational agents not included in this trial and throughout the duration of this trial; within at least 5 half-lives of previous therapy for smoldering myeloma at start of this trial.
- Prior therapy for SMM with a proteasome inhibitor.
- Patients with a diagnosis of MM per standard IMWG criteria
- Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy.
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
- Uncontrolled hypertension or diabetes.
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- Females patients who are lactating or have a positive serum pregnancy test during the screening period.
- Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing.
- Patient has ≥ Grade 1 peripheral neuropathy with pain on clinical examination during the screening period.
- Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
- Systemic treatment, within 14 days before study enrollment, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort.
- Ongoing or active systemic infection, known human immunodeficiency virus (HIV) positive, known active hepatitis B virus hepatitis, or known active hepatitis C virus hepatitis.
- Co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
- Psychiatric illness/social situation that would limit compliance with study requirements.
- QTc > 470 milliseconds (msec) on a 12-lead EKG obtained during the Screening period. If a machine reading is above this value, the EKG should be reviewed by a qualified reader and confirmed on a subsequent EKG.
- Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- Failure to have fully recovered (ie, ≤ Grade 1 toxicity) from the reversible effects of prior chemotherapy.
- Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements or GI procedure that could interfere with the oral absorption or tolerance of treatment.
- Major surgery within 14 days prior to enrollment.
- Radiotherapy within 14 days before enrollment. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib.
- Central nervous system involvement (based on clinical assessment).
- Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment.
- No current anti-myeloma bisphosphonate therapy (however, prior bisphosphonates and/or bisphosphonate therapy due to osteoporosis is allowed).
- Patients with Paget's disease of the bone.
- Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Memorial Sloan Kettering Cancer Center
Basking Ridge, New Jersey, 10065
Memorial Sloan Kettering Commack
Commack, New York, 11725
Memorial Sloan Kettering Westchester
Harrison, New York, 10604
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
The purpose of this study is to see what effects, good and/or bad, the combination of ixazomib and dexamethasone has on the patient and the smoldering multiple myeloma.
- Being tested
- Ixazomib (MLN9708), Dexamethasone
- Keywords
- Ixazomib (MLN9708), Dexamethasone, 15-294
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ixazomib (MLN9708)Drug
DexamethasoneDrug
| Study group | Role | What they receive |
|---|---|---|
| Ixazomib (MLN9708) and Dexamethasone | Experimental | Patients with high risk SMM will be enrolled on the pilot study and treated with 2 drug combination (Cycles 1-12 Ixazomib at 4 mg weekly on days 1, 8 and 15, and dexamethasone on days 1, 8, 15 and 22 of 28 day cycle); the dexamethasone dose will be 40 mg/week the first 4 cycles, thereafter 20 mg/week. Receives: Drug: Ixazomib (MLN9708); Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
best response
best overall response rate (PR or better) Stringent Complete Response (sCR) Complete Response as defined below plus: Normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence (presence/absence of clonal cells is based on the kappa/ lambda ratio. Complete Response (CR) Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow Very Good Partial Response (VGPR) Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100mg per 24h Partial Response (PR) ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200mg per 24h. If the serum and urine M-protein are unmeasureable, a ≥50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria
Measured: up to 12 cycles of treatment (28 day cycle)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2016 (estimated)
- Study startFeb 2016
- Primary completion8 May 2024
- Study completion8 May 2024
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.
- More trials run by Memorial Sloan Kettering Cancer CenterThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Sham Mailankody, MBBS, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02697383
- Sponsor's protocol ID
- 15-294
- Status last verified
- May 2024
- First submitted
- 24 Feb 2016
- Last updated
- 13 May 2024
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ixazomib (MLN9708) and Dexamethasone in High Risk Smoldering Multiple Myeloma: A Clinical and Correlative Pilot Study
- ClinicalTrials.gov ID
- NCT02697383
- Acronym / sponsor ID
- 15-294
- Keywords
- Ixazomib (MLN9708), Dexamethasone, 15-294
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Feb 2016 (actual)
- Primary completion
- 8 May 2024 (actual)
- Study completion
- 8 May 2024 (actual)
- First posted
- 3 Mar 2016 (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.
The purpose of this study is to see what effects, good and/or bad, the combination of ixazomib and dexamethasone has on the patient and the smoldering multiple myeloma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ixazomib (MLN9708) and Dexamethasone | Experimental | Drug: Ixazomib (MLN9708), Drug: DexamethasonePatients with high risk SMM will be enrolled on the pilot study and treated with 2 drug combination (Cycles 1-12 Ixazomib at 4 mg weekly on days 1, 8 and 15, and dexamethasone on days 1, 8, 15 and 22 of 28 day cycle); the dexamethasone dose will be 40 mg/week the first 4 cycles, thereafter 20 mg/week. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Patients must have histologically or cytologically confirmed Smoldering Multiple Myeloma confirmed by Department of Pathology, based on the International Myeloma Working Group Criteria
- Serum M-protein ≥3 g/dl and/or bone marrow plasma cells ≥10 %,
- Absence of anemia attributed to the plasma cell disorder*: Hemoglobin >10 g/dl or not more than 2g/dL below the lower limit of normal
- Absence of renal failure attributed to the plasma cell disorder*: calculated creatinine clearance (according to Cockcroft-Gault method, MDRD, or CKD-EPI formulae) > 30 mL/min (or alternatively based on standard creatinine level criteria of 2 mg/dl)
- Absence of hypercalcemia attributed to the plasma cell disorder* (: Ca < 10.5 mg/dl or ≤ 2.5 mmol/L
Key exclusion criteria (25 listed)
- Participation in other clinical trials, including those with other investigational agents not included in this trial and throughout the duration of this trial; within at least 5 half-lives of previous therapy for smoldering myeloma at start of this trial.
- Prior therapy for SMM with a proteasome inhibitor.
- Patients with a diagnosis of MM per standard IMWG criteria
- Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy.
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
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 |
|---|---|---|
| Ixazomib (MLN9708) | Drug | Ixazomib (MLN9708) and Dexamethasone |
| Dexamethasone | Drug | Ixazomib (MLN9708) and Dexamethasone |
Primary outcome
best response
Time frame: up to 12 cycles of treatment (28 day cycle)
best overall response rate (PR or better) Stringent Complete Response (sCR) Complete Response as defined below plus: Normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence (presence/absence of clonal cells is based on the kappa/ lambda ratio. Complete Response (CR) Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow Very Good Partial Response (VGPR) Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100mg per 24h Partial Response (PR) ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200mg per 24h. If the serum and urine M-protein are unmeasureable, a ≥50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2024.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
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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.
Sham Mailankody, MBBS principal investigator
Memorial Sloan Kettering Cancer Center
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ixazomib (MLN9708) and Dexamethasone in people with Multiple Myeloma and High Risk Smoldering Multiple Myeloma, run by Memorial Sloan Kettering Cancer Center at 6 sites 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 31 inclusion and 25 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: finished, as of the sponsor's last update on 13 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
best response (time frame: up to 12 cycles of treatment (28 day cycle)). 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 13 May 2024.