Phase 1/2 Dose Escalation Study in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia

Status:	Completed
Conditions:	Lymphoma, Hematology
Therapuetic Areas:	Hematology, Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	12/8/2017
Start Date:	March 2014
End Date:	November 2017

Phase 1/2 Open-Label, Multiple-dose, Dose-escalation Study to Evaluate the Safety and Tolerability of IMO-8400 in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia

Recent reports have identified a specific oncogenic mutation L265P of the MYD88 gene in
approximately 90% of the patients with Waldenström's macroglobulinemia. MYD88 is a key linker
protein in the signaling pathway of Toll Like Receptors (TLRs) 7, 8, and 9, and IMO-8400 is
an oligonucleotide specifically designed to inhibit TLRs 7,8, and 9. The scientific
hypothesis for use of IMO-8400 to treat patients with Waldenström's macroglobulinemia depends
on the inhibition of mutant MYD88 signaling in the TLR pathway, thereby interrupting the
proliferation of cell populations responsible for the propagation of the disease.

Eligible subjects will be enrolled and assigned to escalating dose cohorts. Treatment will be
administered by subcutaneous injection.

Inclusion Criteria:

Patients must have a diagnosis of relapsed Waldenstrom's Macroglobulinemia.

In addition to the above, key inclusion and exclusion criteria are listed below.

Inclusion Criteria:

1. At least 18 years of age.

2. Agree to use contraception

3. Hemoglobin ≥ 7.5 g/dL, - Absolute neutrophil count ≥ 1.0 x 109/L (1000/mm3), -
Platelets ≥ 50,000/μL

Exclusion Criteria:

1. Is nursing or pregnant

2. Has BMI > 34.9 kg/m2.

3. Has a positive test for human immunodeficiency virus (HIV-1 or -2) hepatitis C virus
(HCV) or hepatitis B surface antigen (HBsAg).

4. Receiving chronic systemic corticosteroid therapy > 20 mg of prednisone daily.

5. Being treated with other anti-cancer therapies (approved or investigational).

6. Has, at the initiation of study drug, received cytotoxic chemotherapy or a Bruton's
tyrosine kinase (BTK)-inhibitor (e.g. ibrutinib) within the past 3 weeks or rituximab
within the past 2 months

7. Has an active infection requiring systemic antibiotics.

8. Has had surgery requiring general anesthesia within 4 weeks of starting the study.

9. Has autoimmune cytopenia (anemia, thrombocytopenia, leukopenia).

10. Has heart failure of Class III or IV.

11. Has sensory or motor neuropathy limiting daily activities.

We found this trial at

sites

Hackensack University

Hackensack, New Jersey 07601

from

Hackensack, NJ