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

NCT04398485 | Completed Phase 1 FDA Drug

• 1 other identifier: ION251-CS1
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 6

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.

Conditions

Relapsed Multiple Myeloma; Refractory Multiple Myeloma

Keywords

multiple myeloma; Relapsed Multiple Myeloma; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (7)

• Safety and Tolerability as Measured by the Incidence of TEAEs

  Up to 28 days from the last dose of study drug

• Incidence of Abnormal Laboratory Values and Vital Signs

  Up to 28 days from the last dose of study drug

• Cmax: Maximum Observed Concentration ION251

  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

  From Baseline up to 28 days from the last dose of study drug

• t1/2: Distribution Half-life of ION251

  From Baseline up to 28 days from the last dose of study drug

Study Arms (1)

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.

Drug: ION251

Interventions

ION251 DRUG

ION251 administered by IV infusion

ION251

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Ionis Pharmaceuticals, Inc.: lead

Study Sites (6)

University of California San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

UCLA Rrmc

Los Angeles, California, 90095, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine in Saint Louis

St Louis, Missouri, 63130, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Related Publications (1)

• 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.

  PMID: 33476575 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2020
• First Posted: May 21, 2020
• Study Start: January 20, 2021
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)