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

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ClinicalTrials.gov Identifier: NCT04398485
Recruitment Status : Recruiting
First Posted : May 21, 2020
Last Update Posted : April 6, 2021
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

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
Relapsed Multiple Myeloma Refractory Multiple Myeloma Drug: ION251 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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : January 20, 2021
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : January 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

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




Primary Outcome Measures :
  1. 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) ]
    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) [ Time Frame: 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 [ Time Frame: Up to 28 days from the last dose of study drug ]
  2. Incidence of Abnormal Laboratory Values and Vital Signs [ Time Frame: Up to 28 days from the last dose of study drug ]
  3. Cmax: Maximum Observed Concentration ION251 [ Time Frame: 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 [ Time Frame: From Baseline up to 28 days from the last dose of study drug ]
  5. t1/2: Distribution Half-life of ION251 [ Time Frame: From Baseline up to 28 days from the last dose of study drug ]
  6. Trough Concentration of ION251 [ Time Frame: From Baseline up to 28 days from the last dose of study drug ]
  7. Urine 0-24 Hour (hr) Excretion of ION251 [ Time Frame: Up to 12 months from the last dose of study drug ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04398485


Contacts
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Contact: Ionis Pharmaceuticals 800-679-4747 patients@ionisph.com

Locations
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United States, Alabama
The University of Alabama at Birmingham Comprehensive Cancer Center Recruiting
Birmingham, Alabama, United States, 35233
United States, Arizona
Mayo Clinic - Arizona Recruiting
Phoenix, Arizona, United States, 85054
United States, California
University of California San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
United States, Florida
Mayo Clinic - Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
United States, Maryland
Regional Cancer Care Associates - Center for Cancer and Blood Disorders - Bethesda Recruiting
Bethesda, Maryland, United States, 20817
The Center for Cancer and Blood Disorders Recruiting
Bethesda, Maryland, United States, 20817
United States, Minnesota
Mayo Clinic - Rochester Recruiting
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine in Saint Louis Recruiting
Saint Louis, Missouri, United States, 63130
United States, North Carolina
Levine Cancer Institute Recruiting
Charlotte, North Carolina, United States, 28204
United States, Wisconsin
Froedtert Hospital Recruiting
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04398485    
Other Study ID Numbers: ION251-CS1
First Posted: May 21, 2020    Key Record Dates
Last Update Posted: April 6, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.:
multiple myeloma
Relapsed Multiple Myeloma
Refractory Multiple Myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases