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

Sponsor
Ionis Pharmaceuticals, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04398485
Collaborator
(none)
80
12
1
35.4
6.7
0.2

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
80 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Study of ION251 Administered by Intravenous Infusion to Patients With Relapsed/Refractory Multiple Myeloma
Actual Study Start Date :
Jan 20, 2021
Anticipated Primary Completion Date :
Jan 1, 2024
Anticipated Study Completion Date :
Jan 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: ION251

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
ION251 administered by IV infusion

Outcome Measures

Primary Outcome Measures

  1. Maximum-Tolerated Dose (MTD) [Up to 28 days from the last dose of study drug in Cycle 1 (each cycle is 28 days)]

    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

  2. Recommended Phase 2 Dose (PR2D) [Up to 28 days from the last dose of study drug]

    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

Secondary Outcome Measures

  1. Safety and Tolerability as Measured by the Incidence of TEAEs [Up to 28 days from the last dose of study drug]

  2. Incidence of Abnormal Laboratory Values and Vital Signs [Up to 28 days from the last dose of study drug]

  3. Cmax: Maximum Observed Concentration ION251 [From Baseline up to 28 days from the last dose of study drug]

  4. 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]

  5. t1/2: Distribution Half-life of ION251 [From Baseline up to 28 days from the last dose of study drug]

  6. Trough Concentration of ION251 [From Baseline up to 28 days from the last dose of study drug]

  7. Urine 0-24 Hour (hr) Excretion of ION251 [Up to 12 months from the last dose of study drug]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

  1. 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

  2. Uncontrolled hypertension (systolic pressure ≥ 160 mm of mercury (mm Hg) and/or diastolic pressure ≥ 100 mm Hg)

  3. Presence of a bleeding disorder or an underlying disease state associated with active bleeding.

Contacts and Locations

Locations

Site City State Country Postal Code
1 The University of Alabama at Birmingham Comprehensive Cancer Center Birmingham Alabama United States 35233
2 Mayo Clinic - Arizona Phoenix Arizona United States 85054
3 University of California San Diego Moores Cancer Center La Jolla California United States 92093
4 Cedars-Sinai Medical Center Los Angeles California United States 90048
5 Mayo Clinic - Jacksonville Jacksonville Florida United States 32224
6 Regional Cancer Care Associates - Center for Cancer and Blood Disorders - Bethesda Bethesda Maryland United States 20817
7 The Center for Cancer and Blood Disorders Bethesda Maryland United States 20817
8 Mayo Clinic - Rochester Rochester Minnesota United States 55905
9 Washington University School of Medicine in Saint Louis Saint Louis Missouri United States 63130
10 New York Presbyterian Hospital New York New York United States 10021
11 Levine Cancer Institute Charlotte North Carolina United States 28204
12 Froedtert Hospital Milwaukee Wisconsin United States 53226

Sponsors and Collaborators

  • Ionis Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT04398485
Other Study ID Numbers:
  • ION251-CS1
First Posted:
May 21, 2020
Last Update Posted:
Oct 14, 2021
Last Verified:
Oct 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
Yes
Keywords provided by Ionis Pharmaceuticals, Inc.
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 14, 2021