Dose Escalation Study in Patients With Relapsed or Refractory DLBCL and MyD88 L265P Mutation

November 13, 2017 updated by: Idera Pharmaceuticals, Inc.

Phase I/II Open-label, Multiple-dose, Dose-escalation Study to Evaluate the Safety and Tolerability of IMO-8400 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Presence of the MyD88 L265P Mutation

Recent reports have identified a specific oncogenic mutation L265P of the MYD88 gene in approximately 30% of the patients with the activated B-cell (ABC) type of Diffuse Large B Cell Lymphoma (DLBCL). MYD88 is an initial adapter linker protein in the signaling pathway of the Toll Like Receptors (TLRs), including the endosomal TLRs 7, 8, and 9, for which the ligands are nucleic acids. IMO-8400 is an oligonucleotide specifically designed to inhibit ligand activation of TLRs 7,8, and 9. Recent studies indicate that in the presence of L265P mutation ligand activation of those TLRs results in markedly increased signaling with subsequent increased cell activation, cell survival, and cell proliferation. The scientific rationale for assessing the use of IMO-8400 to treat patients with DLBCL and the L265P mutation is based on laboratory observations that IMO-8400 inhibits ligand-based activation of cells with the mutation and decreases the survival and proliferation of the cell populations responsible for the propagation of the disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Eligible subjects will be enrolled and assigned to one of five dose cohorts. Treatment will be administered by subcutaneous injection until progression or intolerable toxicity.

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
    • Georgia
      • Atlanta, Georgia, United States, 30306
        • Emory University
    • Illinois
      • Decatur, Illinois, United States, 62526
        • Cancer Care Specialists of Illinois
    • Indiana
      • Lafayette, Indiana, United States, 47905
        • Horizon Bio Advance
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • New York, New York, United States, 10019
        • Columbia University Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44109
        • Cleveland Clinic
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt Ingram Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patients must have a diagnosis of Diffuse Large B Cell Lymphoma (DLBCL) of non-GCB subtype, established according to the World Health Organization (WHO) criteria that has been tested for the MyD88 L265P mutation.

  • In addition to the above, key inclusion and exclusion criteria are listed below.

    1. Be at least 18 years of age
    2. Agree to use contraception

Exclusion Criteria:

  1. Is nursing or pregnant
  2. DLBCL of GCB subtype
  3. Has BMI > 34.9 kg/m2
  4. Has a positive test for human immunodeficiency virus (HIV-1 or -2) hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg)
  5. Receiving chronic systemic corticosteroid therapy > 20 mg of prednisone daily
  6. Being treated with other anti-cancer therapies (approved or investigational)
  7. Has an active infection requiring systemic antibiotics
  8. Has had surgery requiring general anesthesia within 4 weeks of starting the study
  9. Has heart failure of Class III or IV

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IMO-8400
IMO-8400 0.3 mg/kg twice weekly, 0.6 mg/kg twice weekly, or 1.2 mg/kg twice weekly
Drug: IMO-8400
MO-8400 given subcutaneously twice weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Adverse Events, Injection Site Reactions, and Concomitant Medications
Time Frame: Up to 2 years from first patient visit
Frequency of adverse events, injection site reactions, and concomitant medications observed
Up to 2 years from first patient visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Idera Pharmaceuticals, Inc.

Investigators

  • Study Director: Mark Cornfeld, MD, MPH, Idera Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2014

Primary Completion (Actual)

December 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

August 8, 2014

First Submitted That Met QC Criteria

September 25, 2014

First Posted (Estimate)

September 30, 2014

Study Record Updates

Last Update Posted (Actual)

December 12, 2017

Last Update Submitted That Met QC Criteria

November 13, 2017

Last Verified

November 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 8400-402

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Diffuse Large B Cell Lymphoma

Clinical Trials on IMO-8400

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Bulgaria

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe