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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02252146
Recruitment Status : Completed
First Posted : September 30, 2014
Results First Posted : November 14, 2017
Last Update Posted : December 12, 2017
Sponsor:
Information provided by (Responsible Party):
Idera Pharmaceuticals, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Diffuse Large B Cell Lymphoma Drug: IMO-8400 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : June 2014
Actual Primary Completion Date : December 2016
Actual Study Completion Date : December 2016


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




Primary Outcome Measures :
  1. 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



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:

  • 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

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): NCT02252146


Locations
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United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30306
United States, Illinois
Cancer Care Specialists of Illinois
Decatur, Illinois, United States, 62526
United States, Indiana
Horizon Bio Advance
Lafayette, Indiana, United States, 47905
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Columbia University Medical Center
New York, New York, United States, 10019
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44109
United States, Tennessee
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Idera Pharmaceuticals, Inc.
Investigators
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Study Director: Mark Cornfeld, MD, MPH Idera Pharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by Idera Pharmaceuticals, Inc.:
Study Protocol  [PDF] January 29, 2016
Statistical Analysis Plan  [PDF] November 11, 2016


Additional Information:
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Responsible Party: Idera Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02252146     History of Changes
Other Study ID Numbers: 8400-402
First Posted: September 30, 2014    Key Record Dates
Results First Posted: November 14, 2017
Last Update Posted: December 12, 2017
Last Verified: November 2017
Keywords provided by Idera Pharmaceuticals, Inc.:
DLBCL
MYD88 L265P
Lymphoma
Diffuse Large B Cell Lymphoma
Idera
IMO 8400
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin