Clinical Trials /

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

NCT04398485

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
ION251ION251

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

NameTypeDescriptionInterventions
ION251ExperimentalIn 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.
  • ION251

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 < 75 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

April 6, 2021