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

Diffuse Large B Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02252146
• Other study ID #: 8400-402
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: August 8, 2014
• Last updated: November 13, 2017
• Start date: June 2014
• Est. completion date: December 2016

Study information

• Verified date: November 2017
• Source: Idera Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• IMO-8400
MO-8400 given subcutaneously twice weekly

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Cleveland Clinic	Cleveland	Ohio
United States	Cancer Care Specialists of Illinois	Decatur	Illinois
United States	UCLA Medical Center	El Pueblo De Nuestra Señora De Los Ángeles De Porciúncula	California
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	Horizon Bio Advance	Lafayette	Indiana
United States	Vanderbilt Ingram Cancer Center	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University	San Luis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Idera Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events, Injection Site Reactions, and Concomitant Medications	Frequency of adverse events, injection site reactions, and concomitant medications observed	Up to 2 years from first patient visit

External Links

•   Genetic and Rare Diseases Information Center