Multiple MyelomaPhase 1/2SLAMNCT02389543
Study of Selinexor (KPT- 330), Lenalidomide, & Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients
A Phase 1/2 study testing Selinexor, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Karyopharm Therapeutics Inc.
Trial summary
This is an open-label, randomized clinical study with two stages to assess the maximum tolerated dose (MTD), efficacy, and safety of selinexor, lenalidomide, and dexamethasone (SLd) in patients with relapsed/refractory (RR) multiple myeloma (MM). The stages are dose escalation (Phase 1) and expansion (Phase 2). 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?
- Selinexor, Lenalidomide and Dexamethasone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jul 2015to Feb 2018
- Phase
- Phase 1/2
- 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
- Histologically confirmed diagnosis, measurable disease and evidence of disease progression of MM.
- Relapsed or refractory to the most recently received therapy. Relapsed is defined as documented evidence of PD after achieving at least SD for ≥ 1 cycle. Refractory disease is defined as ≤ 25% response (i.e., patients never achieved minimal response or better) or progression during therapy or within 60 days after completion of therapy.
- Symptomatic MM, based on IMWG guidelines. Patients must have measurable disease.
Who cannot join
- Smoldering MM.
- Multiple myeloma that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead.
- Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
- Active MM involving the central nervous system (CNS).
About this study
Official title: A Multi-Center, Phase 1/2, Open-Label Study of Selinexor (KPT- 330), Lenalidomide, and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
This is an open-label, randomized clinical study with two stages to assess the maximum tolerated dose (MTD), efficacy, and safety of selinexor, lenalidomide, and dexamethasone (SLd) in patients with relapsed/refractory (RR) multiple myeloma (MM). The stages are dose escalation (Phase 1) and expansion (Phase 2).
Read the detailed description
In Phase 1 (Dose Escalation), patients will be randomized to either once-weekly (Arm A) or twice- weekly (Arm B) dosing with selinexor. Dose escalation will be performed within each arm for both lenalidomide and selinexor to determine the selinexor MTD for that arm. Each arm will be expanded until approximately 17 patients have been treated at the MTD in each arm. The Sponsor and Investigator will review the MTD, efficacy, and safety data from Phase 1 to determine which dose schedule (Arm A or B) to be used as the RP2D dose in the Expansion Phase.
In Phase 2 (Expansion), patients who had received the MTD dose that was nominated for RP2D will continue at the same dose. Patients who did not receive the RP2D for that arm will stay on their Phase 1 dose. Additional patients will be accrued, as needed, to achieve the target population size of approximately 34 patients at the RP2D.
- Conditions
- Multiple Myeloma
- Being tested
- Selinexor, Lenalidomide, Dexamethasone
- Keywords
- KPT-330, Selinexor, Multiple Myeloma, Relapsed/refractory, Lenalidomide, Dexamethasone, Karyopharm
- 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.
SelinexorDrug
Also called KPT-330
Two different dosing schedules will be tested, once weekly and twice weekly. If the selinexor 80 mg dose is tolerated, the dose will be increased to 100 mg.
LenalidomideDrug
In both arms, lenalidomide will be started at 15 mg/day (Dose Level 1) and, if tolerated per DLT criteria, will be escalated to 25 mg/day (Dose Level 2).
DexamethasoneDrug
Dexamethasone will be given in combination with each dose of selinexor on the once weekly treatment arm.
For the twice weekly arm dexamethasone will be given in combination with each dose of selinexor and will also be given without selinexor on Days 22 and 24.
| Study group | Role | What they receive |
|---|---|---|
| A: Selinexor (1x/week), Lenalidomide, & Dexamethasone | Experimental | Lenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per dose-limiting toxicity (DLT criteria,) it will be increased to 25 mg for that arm. Selinexor will be started at 80 mg (~45 mg/m2) once weekly in combination with dexamethasone 40 mg once weekly with each dose of selinexor. If the selinexor 80 mg dose is tolerated per DLT criteria, the dose will be increased to 100 mg (~60 mg/m2) and evaluated for MTD, tolerability and efficacy. Receives: Drug: Selinexor; Drug: Lenalidomide; Drug: Dexamethasone |
| B: Selinexor (2x/week), Lenalidomide, & Dexamethasone | Experimental | Lenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per DLT criteria, it will be increased to 25 mg for that arm. Selinexor will be started at 60 mg (~35 mg/m2) twice weekly in combination with dexamethasone 20 mg twice weekly with each dose of selinexor; dexamethasone 20 mg will also be given, without selinexor, on Days 22 and 24. If the selinexor 60 mg dose is tolerated per DLT criteria, the dose will be increased to 80 mg (~45 mg/m2) and evaluated for MTD, tolerability and efficacy. Receives: Drug: Selinexor; Drug: Lenalidomide; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine maximum tolerated dose (MTD)
Determine the maximum tolerated dose (MTD) of selinexor in the combination SLd in patients with RR MM, as determined by dose limiting toxicities (DLTs), efficacy, and safety
Measured: 12 months
Overall response rate (ORR)
According to the International Myeloma Working Group [IMWG] criteria, Overall Response Rate (ORR) includes: stringent complete response [sCR], complete response [CR], very good partial response [VGPR], and partial response [PR]
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2015 (estimated)
- Study startJul 2015
- Primary completionJan 2018 (estimated)
- Study completionFeb 2018 (estimated)
Why it stopped: Terminated this trial and added a Lenalidomide arm to KCP-330-017
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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karyopharm Therapeutics Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02389543
- Sponsor's protocol ID
- KCP-330-011
- Acronym
- SLAM
- Status last verified
- Jan 2023
- First submitted
- 10 Mar 2015
- Last updated
- 26 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Phase 1/2, Open-Label Study of Selinexor (KPT- 330), Lenalidomide, and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02389543
- Acronym / sponsor ID
- SLAM / KCP-330-011
- Conditions
- Multiple Myeloma
- Keywords
- KPT-330, Selinexor, Multiple Myeloma, Relapsed/refractory, Lenalidomide, Dexamethasone, Karyopharm
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Terminated this trial and added a Lenalidomide arm to KCP-330-017
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Karyopharm Therapeutics IncIndustry (pharma, biotech, devices)
- Study start
- Jul 2015
- Primary completion
- Jan 2018 (estimated)
- Study completion
- Feb 2018 (estimated)
- First posted
- 17 Mar 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 is an open-label, randomized clinical study with two stages to assess the maximum tolerated dose (MTD), efficacy, and safety of selinexor, lenalidomide, and dexamethasone (SLd) in patients with relapsed/refractory (RR) multiple myeloma (MM). The stages are dose escalation (Phase 1) and expansion (Phase 2).
Detailed description
In Phase 1 (Dose Escalation), patients will be randomized to either once-weekly (Arm A) or twice- weekly (Arm B) dosing with selinexor. Dose escalation will be performed within each arm for both lenalidomide and selinexor to determine the selinexor MTD for that arm. Each arm will be expanded until approximately 17 patients have been treated at the MTD in each arm. The Sponsor and Investigator will review the MTD, efficacy, and safety data from Phase 1 to determine which dose schedule (Arm A or B) to be used as the RP2D dose in the Expansion Phase.
In Phase 2 (Expansion), patients who had received the MTD dose that was nominated for RP2D will continue at the same dose. Patients who did not receive the RP2D for that arm will stay on their Phase 1 dose. Additional patients will be accrued, as needed, to achieve the target population size of approximately 34 patients at the RP2D.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: Selinexor (1x/week), Lenalidomide, & Dexamethasone | Experimental | Drug: Selinexor, Drug: Lenalidomide, Drug: DexamethasoneLenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per dose-limiting toxicity (DLT criteria,) it will be increased to 25 mg for that arm. Selinexor will be started at 80 mg (~45 mg/m2) once weekly in combination with dexamethasone 40 mg once weekly with each dose of selinexor. If the selinexor 80 mg dose is tolerated per DLT criteria, the dose will be increased to 100 mg (~60 mg/m2) and evaluated for MTD, tolerability and efficacy. |
| B: Selinexor (2x/week), Lenalidomide, & Dexamethasone | Experimental | Drug: Selinexor, Drug: Lenalidomide, Drug: DexamethasoneLenalidomide will be dosed initially at 15 mg daily, and if that dose is tolerated per DLT criteria, it will be increased to 25 mg for that arm. Selinexor will be started at 60 mg (~35 mg/m2) twice weekly in combination with dexamethasone 20 mg twice weekly with each dose of selinexor; dexamethasone 20 mg will also be given, without selinexor, on Days 22 and 24. If the selinexor 60 mg dose is tolerated per DLT criteria, the dose will be increased to 80 mg (~45 mg/m2) and evaluated for MTD, tolerability and efficacy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Histologically confirmed diagnosis, measurable disease and evidence of disease progression of MM.
- Relapsed or refractory to the most recently received therapy. Relapsed is defined as documented evidence of PD after achieving at least SD for ≥ 1 cycle. Refractory disease is defined as ≤ 25% response (i.e., patients never achieved minimal response or better) or progression during therapy or within 60 days after completion of therapy.
- Symptomatic MM, based on IMWG guidelines. Patients must have measurable disease.
Key exclusion criteria (4 listed)
- Smoldering MM.
- Multiple myeloma that does not express M-protein or FLC (i.e., non-secretory MM is excluded), and quantitative immunoglobulin levels cannot be used instead.
- Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome
- Active MM involving the central nervous system (CNS).
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 |
|---|---|---|
| SelinexorAlso: KPT-330Two different dosing schedules will be tested, once weekly and twice weekly. If the selinexor 80 mg dose is tolerated, the dose will be increased to 100 mg. | Drug | A: Selinexor (1x/week), Lenalidomide, & Dexamethasone, B: Selinexor (2x/week), Lenalidomide, & Dexamethasone |
| LenalidomideIn both arms, lenalidomide will be started at 15 mg/day (Dose Level 1) and, if tolerated per DLT criteria, will be escalated to 25 mg/day (Dose Level 2). | Drug | A: Selinexor (1x/week), Lenalidomide, & Dexamethasone, B: Selinexor (2x/week), Lenalidomide, & Dexamethasone |
| DexamethasoneDexamethasone will be given in combination with each dose of selinexor on the once weekly treatment arm. For the twice weekly arm dexamethasone will be given in combination with each dose of selinexor and will also be given without selinexor on Days 22 and 24. | Drug | A: Selinexor (1x/week), Lenalidomide, & Dexamethasone, B: Selinexor (2x/week), Lenalidomide, & Dexamethasone |
Primary outcome
Determine maximum tolerated dose (MTD)
Time frame: 12 months
Determine the maximum tolerated dose (MTD) of selinexor in the combination SLd in patients with RR MM, as determined by dose limiting toxicities (DLTs), efficacy, and safety
Overall response rate (ORR)
Time frame: 12 months
According to the International Myeloma Working Group [IMWG] criteria, Overall Response Rate (ORR) includes: stringent complete response [sCR], complete response [CR], very good partial response [VGPR], and partial response [PR]
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2023.
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Selinexor, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Karyopharm Therapeutics Inc.
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 3 inclusion and 4 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: withdrawn, as of the sponsor's last update on 26 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
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 combined 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.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Determine maximum tolerated dose (MTD) (time frame: 12 months). 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 26 Jan 2023.