Dose Escalation Study in Patients With Relapsed or Refractory DLBCL and 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.

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Key information

Conditions

Diffuse Large B Cell Lymphoma Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

UCLA Medical Center, Los Angeles, California, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Be at least 18 years of age
Agree to use contraception

Exclusion criteria

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

Treatment and study plan

IMO-8400

Drug

MO-8400 given subcutaneously twice weekly

Primary outcomes

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

Sponsors and collaborators

Lead sponsor

Idera Pharmaceuticals, Inc.

Industry

Registry information

Official study 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

Important dates

Study start: 2014
Primary completion: 2016
Study completion: 2016
First posted: Sep 30, 2014
Registry last updated: Dec 12, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed