Clinical trial NCT04398485: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsed Multiple Myeloma
Refractory Multiple Myeloma
Keywords: multiple myeloma
Relapsed Multiple Myeloma
Refractory Multiple Myeloma
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2020-05-21
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Maximum-Tolerated Dose (MTD)
timeFrame: Up to 28 days from the last dose of study drug in Cycle 1 (each cycle is 28 days)
measure: Recommended Phase 2 Dose (PR2D)
timeFrame: Up to 28 days from the last dose of study drug
Secondary outcomes:
measure: Safety and Tolerability as Measured by the Incidence of TEAEs
timeFrame: Up to 28 days from the last dose of study drug
measure: Incidence of Abnormal Laboratory Values and Vital Signs
timeFrame: Up to 28 days from the last dose of study drug
measure: Cmax: Maximum Observed Concentration ION251
timeFrame: From Baseline up to 28 days from the last dose of study drug
measure: AUC[0-t]: Area Under the Plasma Concentration-Time Curve from Hour zero to t of ION251
timeFrame: From Baseline up to 28 days from the last dose of study drug
measure: t1/2: Distribution Half-life of ION251
timeFrame: From Baseline up to 28 days from the last dose of study drug
measure: Trough Concentration of ION251
timeFrame: From Baseline up to 28 days from the last dose of study drug
measure: Urine 0-24 Hour (hr) Excretion of ION251
timeFrame: Up to 12 months from the last dose of study drug
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Rrmc
state: California
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine in Saint Louis
state: Missouri
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
Study officials:
References:
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.