Multiple MyelomaPhase 2NCT02168101
Determining the Feasibility of MLN9708 as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma
A Phase 2 study testing MLN9708 in people with Multiple Myeloma, run by SCRI Development Innovations, LLC at 4 sites in United States.
Trial summary
The purpose of the study is to determine the safety of MLN9708 as maintenance therapy following allogeneic stem cell transplant in patients with multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- MLN9708
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 4 sitesUnited States
- Study dates
- Sep 2014to 1 Feb 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- KEY POINTS:
- Symptomatic multiple myeloma or asymptomatic myeloma with myeloma-related organ damage diagnosed according to standard criteria in patients who received allogeneic transplant due to high-risk prognostic features, such as, but not limited to:
- Chromosome 17p, partial deletion [del(17p)], t(4;14), t(14;16), t(14;20)
- Plasma cell leukemia
- PFS of less than 2 years after autologous stem cell transplant
- Evidence of engraftment of neutrophils (absolute neutrophil count [ANC] >1000 cells/mm3) and platelets (platelets >60,000 cells/mm3) [dose escalation phase] and >50,000 cells/mm3 [dose expansion phase]).
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- Achievement of at least a PR prior to allogeneic stem cell transplant
- Adequate liver and kidney function
- Ability to swallow oral medication
- Absence of gastrointestinal symptoms that precludes oral intake and absorption of MLN9708
- Off antibiotics and amphotericin B formulations, voriconazole or other anti-fungal therapy for the treatment of proven, probable or possible infections
- ECOG of ≤ 2
- Life expectancy ≥3 months
- Ability to understand the nature of this study and give written informed consent
Who cannot join
- Patients with progressive disease when compared to pre-transplant staging as defined by IMWG Uniform Response criteria for Multiple Myeloma.
- Umbilical cord blood transplant
- Patients with > Grade 2 peripheral neuropathy with pain, or ≥ Grade 3 peripheral neuropathy per NCI CTCAE Version 4.0
- Patients with uncontrolled bacterial, viral, or fungal infections
- New York Heart Association (NYHA) Class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
- Patients who are pregnant or breastfeeding
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- Most recent chemotherapy ≤21 days and ≤ Grade 1 chemotherapy-related side effects, with the exception of alopecia
- Use of a study drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of MLN9708. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and administration of MLN9708 is required.
- Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤14 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy
- Major surgical procedures ≤14 days of beginning study drug, or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
- Ongoing or active systemic infection. Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C
- Central Nervous System involvement
- Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
- Systemic treatment with moderate and strong inhibitors of cytochrome P450 (CYP) 1A2, CYP3A, or clinically significant CYP3A inducers, or use of Ginkgo biloba or St. John's wort within 14 days before study drug administration in the study.
- Presence of other active cancers, or history of treatment for invasive cancer ≤5 years. Patients with Stage I cancer who have received definitive local treatment and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
- Graft versus host disease > Grade 2; or GVHD grade 1 or Grade 2 which requires > 0.5 mg/kg methylprednisolone, or equivalent.
- There are additional Inclusion/Exclusion criteria. The Study Center will determine if you meet all criteria and will answer any questions you may have about the trial.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Oncology Hematology Care
Cincinnati, Ohio, 45242
Colorado Blood Cancer Institute
Denver, Colorado, 80218
Tennessee Oncology PLLC
Nashville, Tennessee, 37203
Texas Transplant Institute
San Antonio, Texas, 78229
About this study
Official title: Open-Label Study to Determine the Feasibility of MLN9708 as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma, Followed by an Expansion Phase at the Maximum-Tolerated Dose (MTD) - A Phase II Study
The purpose of the study is to determine the safety of MLN9708 as maintenance therapy following allogeneic stem cell transplant in patients with multiple myeloma.
Read the detailed description
Although multiple myeloma is considered fatal, survival has dramatically improved over the last two decades with the introduction of more effective treatment options. Proteasome inhibitors have an anti-myeloma effect and are often used as either initial treatment or at relapse in patients with multiple myeloma. MLN9708 is an orally bioavailable, potent, reversible inhibitor of the 20S proteasome. Phase I studies have shown MLN9708 to be very well tolerated with minimal peripheral neuropathy. It has also shown impressive anti-myeloma activity in both the relapsed/refractory setting and the upfront setting (Kumar et al. 2011, Berdeja et al. 2011, Richardson et al. 2011). These characteristics make MLN9708 an ideal proteasome inhibitor to use after allogeneic stem cell transplant. In this Phase II, open-label, multicenter, non-randomized study the investigators will investigate the role of MLN9708 as maintenance after allogeneic stem cell transplant in patients with high-risk multiple myeloma, and in patients with multiple myeloma who have relapsed after an autologous stem cell transplant.
- Conditions
- Multiple Myeloma
- Being tested
- MLN9708
- Keywords
- MLN9708, allogeneic stem cell transplant, multiple myeloma, ixazomib, autologous stem cell transplant
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MLN9708Drug
Also called ixazomib
Patients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive MLN9708 orally (PO) as monotherapy on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. Up to 18 patients will be enrolled in a dose-escalation phase to determine the maximum tolerated dose (MTD).
Dose-Escalation Phase: MLN9708 will be administered orally (PO) as monotherapy. Dosing will start at 2.3 mg. If acceptable tolerability is demonstrated, escalations will be made to 3 mg and to a maximum-planned dose (MPD) of 4 mg.
| Study group | Role | What they receive |
|---|---|---|
| MLN9708 - 2.3 mg | Experimental | Patients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive a weekly dose of 2.3 mg of MLN9708 on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. Receives: Drug: MLN9708 |
| MLN9708 - 3 mg | Experimental | Patients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive a weekly dose of 3 mg of MLN9708 on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. Receives: Drug: MLN9708 |
| MLN9708 - 4 mg | Experimental | Patients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive a weekly dose of 4 mg of MLN9708 on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. Receives: Drug: MLN9708 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Phase I Patients Receiving 2.3mg, 3mg, or 4mg MLN9708 Experiencing a Dose-Limiting Toxicity (DLT) to Determine the Maximum Tolerated Dose
The maximum tolerated dose (MTD) of MLN9708 will be determined as the dose at which ≤1 of 6 patients experiences a DLT during one cycle (28 days) of therapy utilizing the National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v4.0
Measured: Collected from day of first dose to the end of the first treatment cycle, up to 28 days
Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety of MLN9708 When Used as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma Multiple Myeloma
Defined as the number of participants with treatment-emergent grade 3/4/5 adverse events/serious adverse events utilizing the National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v4.0 determined to be related to MLN9708.
Measured: Defined as the time from Day 1 of study drug administration until 30 days after treatment completion for up to 2 years.
Secondary outcomes (4)
Median Progression-Free Survival (PFS) at 2 Years Post-maintenance Therapy
PFS is measured from the date of first protocol treatment until date of disease progression or death occurs, or date of last adequate tumor assessment using the International Myeloma Working Group Uniform Response Criteria. IMWG disease progression is defined as an increase of ≥ 25% from the nadir in at least one of the following criteria: 1) serum M-protein, 2) urine M-protein, 3) only in patients with non-measurable serum and urine M-protein levels: difference in involved and uninvolved FLC levels, 4) Bone marrow plasma cell percentage (absolute % must be ≥10%). OR Disease progression also could include development of new lytic bone lesions or increase from baseline in size of lytic bone lesion(s); development of new soft tissue plasmacytoma(s) or definite increase from nadir in existing soft tissue plasmacytomas; or development of hypercalcemia
Measured: every 8 weeks for approximately 24 weeks then every 3 months thereafter for 2 years
Median Overall Survival (OS) at 2 Years Post-allogeneic Stem Cell Transplant (ASCT)
Overall survival is measured as the interval from first study treatment until date of death, or date last known alive.
Measured: every 8 weeks for approximately 24 weeks after ASCT, then every 3 months thereafter for 2 years.
Number of Participants With Incidence of Chronic Graft-versus-host Disease (cGVHD) After Receiving Allogeneic Stem Cell Transplant and Maintenance With MLN9708
Incidence of chronic Graft-versus-host disease GVHD was assessed based on the National Institutes of Health Consensus Development Project on Criteria for Clinical trials in Acute and Chronic Graft-versus-host-disease (Filipovich et al. 2005) from date of randomization until date of first documented progression, or date of death from any cause.
Measured: from date of enrollment every 28 days, up to 2 years
Number of Participants With Incidence of Acute Graft-versus-host Disease (aGVHD) After Receiving Allogeneic Stem Cell Transplant and Maintenance With MLN9708
Incidence of acute Graft-versus-host disease GVHD was assessed based on the National Institutes of Health Consensus Development Project on Criteria for Clinical trials in Acute and Chronic Graft-versus-host-disease (Przepiorka et al. 1995) from date of randomization until date of first documented progression, or date of death from any cause.
Measured: from date of enrollment every 28 days, up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jun 2014 (estimated)
- Study startSep 2014
- Primary completion1 Feb 2019
- Study completion1 Feb 2019
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 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
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Carlos Bachier, MD, Study chair, Texas Transplant Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02168101
- Sponsor's protocol ID
- SCRI MM 42
- Status last verified
- Feb 2020
- First submitted
- 12 Jun 2014
- Last updated
- 27 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-Label Study to Determine the Feasibility of MLN9708 as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma, Followed by an Expansion Phase at the Maximum-Tolerated Dose (MTD) - A Phase II Study
- ClinicalTrials.gov ID
- NCT02168101
- Acronym / sponsor ID
- SCRI MM 42
- Conditions
- Multiple Myeloma
- Keywords
- MLN9708, allogeneic stem cell transplant, multiple myeloma, ixazomib, autologous stem cell transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Millennium Pharmaceuticals, Inc.
- Study start
- Sep 2014
- Primary completion
- 1 Feb 2019 (actual)
- Study completion
- 1 Feb 2019 (actual)
- First posted
- 20 Jun 2014 (estimated)
- Results
- Posted 27 Feb 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 the study is to determine the safety of MLN9708 as maintenance therapy following allogeneic stem cell transplant in patients with multiple myeloma.
Detailed description
Although multiple myeloma is considered fatal, survival has dramatically improved over the last two decades with the introduction of more effective treatment options. Proteasome inhibitors have an anti-myeloma effect and are often used as either initial treatment or at relapse in patients with multiple myeloma. MLN9708 is an orally bioavailable, potent, reversible inhibitor of the 20S proteasome. Phase I studies have shown MLN9708 to be very well tolerated with minimal peripheral neuropathy. It has also shown impressive anti-myeloma activity in both the relapsed/refractory setting and the upfront setting (Kumar et al. 2011, Berdeja et al. 2011, Richardson et al. 2011). These characteristics make MLN9708 an ideal proteasome inhibitor to use after allogeneic stem cell transplant. In this Phase II, open-label, multicenter, non-randomized study the investigators will investigate the role of MLN9708 as maintenance after allogeneic stem cell transplant in patients with high-risk multiple myeloma, and in patients with multiple myeloma who have relapsed after an autologous stem cell transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MLN9708 - 2.3 mg | Experimental | Drug: MLN9708Patients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive a weekly dose of 2.3 mg of MLN9708 on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. |
| MLN9708 - 3 mg | Experimental | Drug: MLN9708Patients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive a weekly dose of 3 mg of MLN9708 on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. |
| MLN9708 - 4 mg | Experimental | Drug: MLN9708Patients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive a weekly dose of 4 mg of MLN9708 on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Symptomatic multiple myeloma or asymptomatic myeloma with myeloma-related organ damage diagnosed according to standard criteria in patients who received allogeneic transplant due to high-risk prognostic features, such as, but not limited to:
- Evidence of engraftment of neutrophils (absolute neutrophil count [ANC] >1000 cells/mm3) and platelets (platelets >60,000 cells/mm3) [dose escalation phase] and >50,000 cells/mm3 [dose expansion phase]).
- Achievement of at least a PR prior to allogeneic stem cell transplant
- Adequate liver and kidney function
- Ability to swallow oral medication
Key exclusion criteria (17 listed)
- Patients with progressive disease when compared to pre-transplant staging as defined by IMWG Uniform Response criteria for Multiple Myeloma.
- Umbilical cord blood transplant
- Patients with > Grade 2 peripheral neuropathy with pain, or ≥ Grade 3 peripheral neuropathy per NCI CTCAE Version 4.0
- Patients with uncontrolled bacterial, viral, or fungal infections
- New York Heart Association (NYHA) Class III or IV heart failure uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
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 |
|---|---|---|
| MLN9708Also: ixazomibPatients will be enrolled between Days 45 and 120 after allogeneic transplant and will receive MLN9708 orally (PO) as monotherapy on Days 1, 8, and 15 of each 28-day cycle for 6 cycles. Up to 18 patients will be enrolled in a dose-escalation phase to determine the maximum tolerated dose (MTD). Dose-Escalation Phase: MLN9708 will be administered orally (PO) as monotherapy. Dosing will start at 2.3 mg. If acceptable tolerability is demonstrated, escalations will be made to 3 mg and to a maximum-planned dose (MPD) of 4 mg. | Drug | MLN9708 - 2.3 mg, MLN9708 - 3 mg, MLN9708 - 4 mg |
Primary outcome
Number of Phase I Patients Receiving 2.3mg, 3mg, or 4mg MLN9708 Experiencing a Dose-Limiting Toxicity (DLT) to Determine the Maximum Tolerated Dose
Time frame: Collected from day of first dose to the end of the first treatment cycle, up to 28 days
The maximum tolerated dose (MTD) of MLN9708 will be determined as the dose at which ≤1 of 6 patients experiences a DLT during one cycle (28 days) of therapy utilizing the National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v4.0
Number of Participants With Grade 3/4/5 Serious Adverse Events and Adverse Events as a Measure of Safety of MLN9708 When Used as Maintenance After Allogeneic Stem Cell Transplant for Multiple Myeloma Multiple Myeloma
Time frame: Defined as the time from Day 1 of study drug administration until 30 days after treatment completion for up to 2 years.
Defined as the number of participants with treatment-emergent grade 3/4/5 adverse events/serious adverse events utilizing the National Cancer Institute Common Technology Criteria for Adverse Events (NCI CTCAE) v4.0 determined to be related to MLN9708.
4 secondary outcomes
Median Progression-Free Survival (PFS) at 2 Years Post-maintenance Therapy
Time frame: every 8 weeks for approximately 24 weeks then every 3 months thereafter for 2 years
Median Overall Survival (OS) at 2 Years Post-allogeneic Stem Cell Transplant (ASCT)
Time frame: every 8 weeks for approximately 24 weeks after ASCT, then every 3 months thereafter for 2 years.
Number of Participants With Incidence of Chronic Graft-versus-host Disease (cGVHD) After Receiving Allogeneic Stem Cell Transplant and Maintenance With MLN9708
Time frame: from date of enrollment every 28 days, up to 2 years
Number of Participants With Incidence of Acute Graft-versus-host Disease (aGVHD) After Receiving Allogeneic Stem Cell Transplant and Maintenance With MLN9708
Time frame: from date of enrollment every 28 days, up to 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Carlos Bachier, MD study chair
Texas Transplant Institute
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MLN9708 in people with Multiple Myeloma, run by SCRI Development Innovations, LLC at 4 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 14 inclusion and 17 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 27 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 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 27 Feb 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 Phase I Patients Receiving 2.3mg, 3mg, or 4mg MLN9708 Experiencing a Dose-Limiting Toxicity (DLT) to Determine the Maximum Tolerated Dose (time frame: Collected from day of first dose to the end of the first treatment cycle, up to 28 days). 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 27 Feb 2020.