Dose Escalation Study in Patients With Relapsed or Refractory DLBCL and MyD88 L265P Mutation
- Registration Number
- NCT02252146
- Lead Sponsor
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 6
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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.
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In addition to the above, key inclusion and exclusion criteria are listed below.
- Be at least 18 years of age
- Agree to use contraception
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description IMO-8400 IMO-8400 IMO-8400 0.3 mg/kg twice weekly, 0.6 mg/kg twice weekly, or 1.2 mg/kg twice weekly
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events, Injection Site Reactions, and Concomitant Medications Up to 2 years from first patient visit Frequency of adverse events, injection site reactions, and concomitant medications observed
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (12)
Emory University
🇺🇸Atlanta, Georgia, United States
Cancer Care Specialists of Illinois
🇺🇸Decatur, Illinois, United States
Horizon Bio Advance
🇺🇸Lafayette, Indiana, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Vanderbilt Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States