Relapsed Multiple MyelomaPhase 1NCT04398485
A Study of ION251 Administered to Patients With Relapsed/Refractory Multiple Myeloma
A Phase 1 study testing ION251 in people with Relapsed Multiple Myeloma and Refractory Multiple Myeloma, run by Ionis Pharmaceuticals, Inc. at 6 sites in United States.
Trial summary
The purpose of this study is to determine the maximum-tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ION251 in patients with relapsed/refractory multiple myeloma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed Multiple Myeloma, Refractory Multiple Myeloma
- What is being tested?
- ION251
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 6 sitesUnited States
- Study dates
- 20 Jan 2021to 30 Sep 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
- Aged ≥ 18 years at the time of informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Measurable multiple myeloma (MM)
- In need of systemic treatment for MM and either is refractory to or has failed treatment with, is intolerant to or has refused, or is not otherwise a candidate in the opinion of the Investigator, for any of the currently available established therapies known to provide clinical benefit in relapsed/refractory MM. Refractory to treatment is defined as documented MM disease progression while on or within 60 days from the last dose (LD) of treatment
Who cannot join
- Screen laboratory results as follows, or any other clinically significant abnormalities in screen laboratory values that would render a participant unsuitable for inclusion
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN)
- Total bilirubin > 1.3 × ULN
- Absolute neutrophil count ≤ 1.0 1000/cubic millimeter (k/mm^3)
- Platelet count < 50 k/mm^3
- Hemoglobin < 8.0 g/dL
Show all 11Show fewer
- Estimated glomerular filtration rate (eGFR) < 50 milliliters per minute (mL/min)/1.73 square meter (m^2)
- Urine albumin creatinine ratio > 100 mg/g
- History of or current plasma cell leukemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, solitary bone or extramedullary plasmacytoma as the only evidence for plasma cell dyscrasia, myelodysplastic syndrome or a myeloproliferative neoplasm
- Uncontrolled hypertension (systolic pressure ≥ 160 mm of mercury (mm Hg) and/or diastolic pressure ≥ 100 mm Hg)
- Presence of a bleeding disorder or an underlying disease state associated with active bleeding.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Levine Cancer Institute
Charlotte, North Carolina, 28204
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
University of California San Diego Moores Cancer Center
La Jolla, California, 92093
Cedars-Sinai Medical Center
Los Angeles, California, 90048
UCLA Rrmc
Los Angeles, California, 90095
Washington University School of Medicine in Saint Louis
St Louis, Missouri, 63130
About this study
Official title: A Phase 1 Study of ION251 Administered by Intravenous Infusion to Patients With Relapsed/Refractory Multiple Myeloma
The purpose of this study is to determine the maximum-tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ION251 in patients with relapsed/refractory multiple myeloma.
Read the detailed description
This is a two-part, multi-center first in human study of ION251 in up to 80 participants. Part 1 will use a 3+3 dose-escalation scheme in sequential cohorts to determine the MTD and RP2D during repeated 28-day treatment cycles. MTD will be determined by the number of participants with AEs meeting the dose-limiting toxicity (DLT) criteria during Cycle 1. The MTD determined in Part 1 will be used with other variables to inform a RP2D for participants proceeding to Part 2 for further assessments in the safety, tolerability and anti-myeloma activity.
- Being tested
- ION251
- Keywords
- multiple myeloma, Relapsed Multiple Myeloma, Refractory Multiple Myeloma
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ION251Drug
ION251 administered by IV infusion
| Study group | Role | What they receive |
|---|---|---|
| ION251 | Experimental | In Part 1, the dose escalation phase, increased amounts of ION251 will be administered at multiple time points by intravenous (IV) infusion during 28-day cycles. In Part 2, the determined RP2D of ION251 will be administered at multiple time points by IV infusion. Receives: Drug: ION251 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum-Tolerated Dose (MTD)
MTD is defined as the maximum dose at which ≤ 1 of 3 evaluable participants experiences a dose-limiting toxicity (DLT) within Cycle 1 and there are 2 of 3 or 2 of 6 evaluable participants in the next higher-dose level experiencing a DLT within Cycle 1. If no dose in the dose-escalation has 2 of 3 or 2 of 6 evaluable participants experiencing a DLT, the highest dose level is considered the MTD
Measured: Up to 28 days from the last dose of study drug in Cycle 1 (each cycle is 28 days)
Recommended Phase 2 Dose (PR2D)
RP2D is chosen based on the dose response and exposure-response analyses of the pooled clinical PK, PD, safety results, and anti-myeloma activity from both Part 1 and Part 2
Measured: Up to 28 days from the last dose of study drug
Secondary outcomes (7)
Safety and Tolerability as Measured by the Incidence of TEAEs
Measured: Up to 28 days from the last dose of study drug
Incidence of Abnormal Laboratory Values and Vital Signs
Measured: Up to 28 days from the last dose of study drug
Cmax: Maximum Observed Concentration ION251
Measured: From Baseline up to 28 days from the last dose of study drug
AUC[0-t]: Area Under the Plasma Concentration-Time Curve from Hour zero to t of ION251
Measured: From Baseline up to 28 days from the last dose of study drug
t1/2: Distribution Half-life of ION251
Measured: From Baseline up to 28 days from the last dose of study drug
Trough Concentration of ION251
Measured: From Baseline up to 28 days from the last dose of study drug
Urine 0-24 Hour (hr) Excretion of ION251
Measured: Up to 12 months from the last dose of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2020
- Study start20 Jan 2021
- Primary completion30 Sep 2024
- Study completion30 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsed Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by Ionis Pharmaceuticals, Inc.The 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ionis Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04398485
- Sponsor's protocol ID
- ION251-CS1
- Status last verified
- Oct 2024
- First submitted
- 11 May 2020
- Last updated
- 31 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mondala PK, Vora AA, Zhou T, Lazzari E, Ladel L, Luo X, Kim Y, Costello C, MacLeod AR, Jamieson CHM, Crews LA. Selective antisense oligonucleotide inhibition of human IRF4 prevents malignant myeloma regeneration via cell cycle disruption. Cell Stem Cell. 2021 Apr 1;28(4):623-636.e9. doi: 10.1016/j.stem.2020.12.017. Epub 2021 Jan 20.
PubMed 33476575
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study of ION251 Administered by Intravenous Infusion to Patients With Relapsed/Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT04398485
- Acronym / sponsor ID
- ION251-CS1
- Keywords
- multiple myeloma, Relapsed Multiple Myeloma, Refractory Multiple Myeloma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Ionis Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 20 Jan 2021 (actual)
- Primary completion
- 30 Sep 2024 (actual)
- Study completion
- 30 Sep 2024 (actual)
- First posted
- 21 May 2020 (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 maximum-tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of ION251 in patients with relapsed/refractory multiple myeloma.
Detailed description
This is a two-part, multi-center first in human study of ION251 in up to 80 participants. Part 1 will use a 3+3 dose-escalation scheme in sequential cohorts to determine the MTD and RP2D during repeated 28-day treatment cycles. MTD will be determined by the number of participants with AEs meeting the dose-limiting toxicity (DLT) criteria during Cycle 1. The MTD determined in Part 1 will be used with other variables to inform a RP2D for participants proceeding to Part 2 for further assessments in the safety, tolerability and anti-myeloma activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ION251 | Experimental | Drug: ION251In Part 1, the dose escalation phase, increased amounts of ION251 will be administered at multiple time points by intravenous (IV) infusion during 28-day cycles. In Part 2, the determined RP2D of ION251 will be administered at multiple time points by IV infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Aged ≥ 18 years at the time of informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Measurable multiple myeloma (MM)
- In need of systemic treatment for MM and either is refractory to or has failed treatment with, is intolerant to or has refused, or is not otherwise a candidate in the opinion of the Investigator, for any of the currently available established therapies known to provide clinical benefit in relapsed/refractory MM. Refractory to treatment is defined as documented MM disease progression while on or within 60 days from the last dose (LD) of treatment
Key exclusion criteria (11 listed)
- Screen laboratory results as follows, or any other clinically significant abnormalities in screen laboratory values that would render a participant unsuitable for inclusion
- History of or current plasma cell leukemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, and skin changes) syndrome, solitary bone or extramedullary plasmacytoma as the only evidence for plasma cell dyscrasia, myelodysplastic syndrome or a myeloproliferative neoplasm
- Uncontrolled hypertension (systolic pressure ≥ 160 mm of mercury (mm Hg) and/or diastolic pressure ≥ 100 mm Hg)
- Presence of a bleeding disorder or an underlying disease state associated with active bleeding.
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 |
|---|---|---|
| ION251ION251 administered by IV infusion | Drug | ION251 |
Primary outcome
Maximum-Tolerated Dose (MTD)
Time frame: Up to 28 days from the last dose of study drug in Cycle 1 (each cycle is 28 days)
MTD is defined as the maximum dose at which ≤ 1 of 3 evaluable participants experiences a dose-limiting toxicity (DLT) within Cycle 1 and there are 2 of 3 or 2 of 6 evaluable participants in the next higher-dose level experiencing a DLT within Cycle 1. If no dose in the dose-escalation has 2 of 3 or 2 of 6 evaluable participants experiencing a DLT, the highest dose level is considered the MTD
Recommended Phase 2 Dose (PR2D)
Time frame: Up to 28 days from the last dose of study drug
RP2D is chosen based on the dose response and exposure-response analyses of the pooled clinical PK, PD, safety results, and anti-myeloma activity from both Part 1 and Part 2
7 secondary outcomes
Safety and Tolerability as Measured by the Incidence of TEAEs
Time frame: Up to 28 days from the last dose of study drug
Incidence of Abnormal Laboratory Values and Vital Signs
Time frame: Up to 28 days from the last dose of study drug
Cmax: Maximum Observed Concentration ION251
Time frame: From Baseline up to 28 days from the last dose of study drug
AUC[0-t]: Area Under the Plasma Concentration-Time Curve from Hour zero to t of ION251
Time frame: From Baseline up to 28 days from the last dose of study drug
t1/2: Distribution Half-life of ION251
Time frame: From Baseline up to 28 days from the last dose of study drug
Trough Concentration of ION251
Time frame: From Baseline up to 28 days from the last dose of study drug
Urine 0-24 Hour (hr) Excretion of ION251
Time frame: Up to 12 months from the last dose of study drug
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 31 Oct 2024.
- Derived from this study: PubMed 33476575Mondala PK, Vora AA, Zhou T, Lazzari E, Ladel L, Luo X, Kim Y, Costello C, MacLeod AR, Jamieson CHM, Crews LA. Selective antisense oligonucleotide inhibition of human IRF4 prevents malignant myeloma regeneration via cell cycle disruption. Cell Stem Cell. 2021 Apr 1;28(4):623-636.e9. doi: 10.1016/j.stem.2020.12.017. Epub 2021 Jan 20.
- Individual participant dataSharing planned: No
Related trials for Relapsed Multiple Myeloma
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 3
A Trial to Learn How Well Linvoseltamab Works Compared to the Combination of Elotuzumab, Pomalidomide and Dexamethasone for Adult Participants With Relapsed/Refractory Multiple Myeloma
Relapsed Refractory Multiple Myeloma (RRMM)
RecruitingPhase 1/2
A Trial to Study if REGN17372 in Combination With Linvoseltamab is Tolerable for Adult Participants With Relapsed/Refractory Multiple Myeloma
Relapsed Refractory Multiple Myeloma (RRMM)
RecruitingPhase 1
A Study to Examine the Effects of Novel Therapy Linvoseltamab in Combination With Other Cancer Treatments for Adult Participants With Multiple Myeloma That is Resistant to Current Standard of Care Treatments
Multiple Myeloma
RecruitingObservational study
Long-term Evaluation and Follow-up Care of Patients Treated With Stem Cell Transplants
Graft-versus-leukemia, Graft vs Host Disease
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.
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 ION251 in people with Relapsed Multiple Myeloma and Refractory Multiple Myeloma, run by Ionis Pharmaceuticals, Inc. 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 4 inclusion and 11 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 31 Oct 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?
Maximum-Tolerated Dose (MTD) (time frame: Up to 28 days from the last dose of study drug in Cycle 1 (each cycle is 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?
On the ClinicalTrials.gov record for NCT04398485, which also lists 1 linked publication.
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 31 Oct 2024.