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

Status:	Completed
Conditions:	Lymphoma
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	12/14/2017
Start Date:	June 2014
End Date:	December 2016

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

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.

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.

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

We found this trial at

sites

The Mayo Clinic

Rochester, Minnesota 55905

Principal Investigator: Grzegorz Nowakowski, M.D.

from

Rochester, MN