Back to resultsA Study of ION251 Administered to Patients With Relapsed/Refractory Multiple Myeloma
Primary Purpose
Relapsed Multiple Myeloma, Refractory Multiple Myeloma
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ION251
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed Multiple Myeloma focused on measuring multiple myeloma, Relapsed Multiple Myeloma, Refractory Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
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
- 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.
Sites / Locations
- University of California San Diego Moores Cancer CenterRecruiting
- Cedars-Sinai Medical CenterRecruiting
- UCLA RrmcRecruiting
- Barbara Ann Karmanos Cancer InstituteRecruiting
- Washington University School of Medicine in Saint LouisRecruiting
- Levine Cancer InstituteRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ION251
Arm Description
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.
Outcomes
Primary Outcome Measures
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
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
Secondary Outcome Measures
Safety and Tolerability as Measured by the Incidence of TEAEs
Incidence of Abnormal Laboratory Values and Vital Signs
Cmax: Maximum Observed Concentration ION251
AUC[0-t]: Area Under the Plasma Concentration-Time Curve from Hour zero to t of ION251
t1/2: Distribution Half-life of ION251
Trough Concentration of ION251
Urine 0-24 Hour (hr) Excretion of ION251
Full Information
NCT ID
NCT04398485
First Posted
May 11, 2020
Last Updated
October 18, 2023
Sponsor
Ionis Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04398485
Brief Title
A Study of ION251 Administered to Patients With Relapsed/Refractory Multiple Myeloma
Official Title
A Phase 1 Study of ION251 Administered by Intravenous Infusion to Patients With Relapsed/Refractory Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 20, 2021 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ionis Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed Multiple Myeloma, Refractory Multiple Myeloma
Keywords
multiple myeloma, Relapsed Multiple Myeloma, Refractory Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ION251
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ION251
Intervention Description
ION251 administered by IV infusion
Primary Outcome Measure Information:
Title
Maximum-Tolerated Dose (MTD)
Description
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
Time Frame
Up to 28 days from the last dose of study drug in Cycle 1 (each cycle is 28 days)
Title
Recommended Phase 2 Dose (PR2D)
Description
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
Time Frame
Up to 28 days from the last dose of study drug
Secondary Outcome Measure Information:
Title
Safety and Tolerability as Measured by the Incidence of TEAEs
Time Frame
Up to 28 days from the last dose of study drug
Title
Incidence of Abnormal Laboratory Values and Vital Signs
Time Frame
Up to 28 days from the last dose of study drug
Title
Cmax: Maximum Observed Concentration ION251
Time Frame
From Baseline up to 28 days from the last dose of study drug
Title
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
Title
t1/2: Distribution Half-life of ION251
Time Frame
From Baseline up to 28 days from the last dose of study drug
Title
Trough Concentration of ION251
Time Frame
From Baseline up to 28 days from the last dose of study drug
Title
Urine 0-24 Hour (hr) Excretion of ION251
Time Frame
Up to 12 months from the last dose of study drug
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ionis Pharmaceuticals
Phone
(844) 923-2998
Email
ionisNCT04398485study@clinicaltrialmedia.com
Facility Information:
Facility Name
University of California San Diego Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Individual Site Status
Recruiting
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Individual Site Status
Recruiting
Facility Name
UCLA Rrmc
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Individual Site Status
Recruiting
Facility Name
Washington University School of Medicine in Saint Louis
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63130
Country
United States
Individual Site Status
Recruiting
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
33476575
Citation
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.
Results Reference
derived
Learn more about this trial
A Study of ION251 Administered to Patients With Relapsed/Refractory Multiple Myeloma
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