Clinical trial NCT02252146: Dose Escalation Study in Patients With Relapsed or Refractory DLBCL and MyD88 L265P Mutation
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Diffuse Large B Cell Lymphoma
Keywords: DLBCL
MYD88 L265P
Lymphoma
Diffuse Large B Cell Lymphoma
Idera
IMO 8400
Lead sponsor: Idera Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2014-09-30
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants With Adverse Events, Injection Site Reactions, and Concomitant Medications
timeFrame: Up to 2 years from first patient visit
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Decatur
country: United States
facility: Cancer Care Specialists of Illinois
state: Illinois
city: Lafayette
country: United States
facility: Horizon Bio Advance
state: Indiana
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Idera Pharmaceuticals, Inc.
name: Mark Cornfeld, MD, MPH
role: STUDY_DIRECTOR
References: