Description:
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.
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
ION251-CS1
- NCT ID:
NCT04398485
Conditions
- Relapsed Multiple Myeloma
- Refractory Multiple Myeloma
Interventions
Drug | Synonyms | Arms |
---|
ION251 | | ION251 |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
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. | |
Eligibility Criteria
Inclusion Criteria:
1. Aged ≥ 18 years at the time of informed consent
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
3. Measurable multiple myeloma (MM)
4. 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:
1. 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
2. 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
3. Uncontrolled hypertension (systolic pressure ≥ 160 mm of mercury (mm Hg) and/or
diastolic pressure ≥ 100 mm Hg)
4. Presence of a bleeding disorder or an underlying disease state associated with active
bleeding.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
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) |
Safety Issue: | |
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 |
Secondary Outcome Measures
Measure: | Safety and Tolerability as Measured by the Incidence of TEAEs |
Time Frame: | Up to 28 days from the last dose of study drug |
Safety Issue: | |
Description: | |
Measure: | Incidence of Abnormal Laboratory Values and Vital Signs |
Time Frame: | Up to 28 days from the last dose of study drug |
Safety Issue: | |
Description: | |
Measure: | Cmax: Maximum Observed Concentration ION251 |
Time Frame: | From Baseline up to 28 days from the last dose of study drug |
Safety Issue: | |
Description: | |
Measure: | 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 |
Safety Issue: | |
Description: | |
Measure: | t1/2: Distribution Half-life of ION251 |
Time Frame: | From Baseline up to 28 days from the last dose of study drug |
Safety Issue: | |
Description: | |
Measure: | Trough Concentration of ION251 |
Time Frame: | From Baseline up to 28 days from the last dose of study drug |
Safety Issue: | |
Description: | |
Measure: | Urine 0-24 Hour (hr) Excretion of ION251 |
Time Frame: | Up to 12 months from the last dose of study drug |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Ionis Pharmaceuticals, Inc. |
Trial Keywords
- multiple myeloma
- Relapsed Multiple Myeloma
- Refractory Multiple Myeloma
Last Updated
August 9, 2021