A Study of ION251 Administered to Patients With Relapsed/Refractory Multiple Myeloma

Refractory Multiple Myeloma Clinical Trial

Official title:

A Phase 1 Study of ION251 Administered by Intravenous Infusion to Patients With Relapsed/Refractory Multiple Myeloma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04398485
• Other study ID #: ION251-CS1
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: January 20, 2021
• Est. completion date: January 2024

Study information

• Verified date: December 2023
• Source: Ionis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 23
• Est. completion date: January 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Refractory Multiple Myeloma
• Relapsed Multiple Myeloma

Intervention

Drug:
• ION251
ION251 administered by IV infusion

Locations

Country	Name	City	State
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	University of California San Diego Moores Cancer Center	La Jolla	California
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	UCLA Rrmc	Los Angeles	California
United States	Washington University School of Medicine in Saint Louis	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Ionis Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Up to 28 days from the last dose of study drug in Cycle 1 (each cycle is 28 days)
Primary	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	Up to 28 days from the last dose of study drug
Secondary	Safety and Tolerability as Measured by the Incidence of TEAEs		Up to 28 days from the last dose of study drug
Secondary	Incidence of Abnormal Laboratory Values and Vital Signs		Up to 28 days from the last dose of study drug
Secondary	Cmax: Maximum Observed Concentration ION251		From Baseline up to 28 days from the last dose of study drug
Secondary	AUC[0-t]: Area Under the Plasma Concentration-Time Curve from Hour zero to t of ION251		From Baseline up to 28 days from the last dose of study drug
Secondary	t1/2: Distribution Half-life of ION251		From Baseline up to 28 days from the last dose of study drug
Secondary	Trough Concentration of ION251		From Baseline up to 28 days from the last dose of study drug
Secondary	Urine 0-24 Hour (hr) Excretion of ION251		Up to 12 months from the last dose of study drug