This trial is active, not recruiting.

Condition diffuse large b cell lymphoma
Treatment imo-8400 given subcutaneously either weekly or twice weekly
Phase phase 1/phase 2
Sponsor Idera Pharmaceuticals, Inc.
Start date June 2014
End date December 2017
Trial size 6 participants
Trial identifier NCT02252146, 8400-402


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.

United States California, Georgia, Massachusetts, Minnesota, New York, Ohio, Tennessee, and Texas
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Experimental cohorts A1, A2, and A3
imo-8400 given subcutaneously either weekly or twice weekly

Primary Outcomes

Safety and tolerability of IMO-8400 in patients with the non-germinal center B (GCB) subtype of Diffuse Large B-Cell Lymphoma (DLBCL)
time frame: Up to 2 years from first patient visit

Secondary Outcomes

Assess the treatment effect (clinical activity)
time frame: Up to 2 years from first patient visit
Identify a dosage of IMO-8400 for further evaluation
time frame: Up to 2 years from first patient visit
Characterize the pharmacokinetics of escalating dosages of IMO-8400
time frame: Up to 2 years from first patient visit

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Idera Pharmaceuticals, Inc..