Phase 1/2 Dose Escalation Study in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia (8400-401)

Idera Pharmaceuticals

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Waldenstrom's Macroglobulinemia

Treatments: Drug: IMO-8400

Study type: Interventional

Funder types: Industry

Identifiers

NCT02092909

8400-401

Details and patient eligibility

About

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.

Full description

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

Enrollment: 31 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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31 participants in 1 patient group

IMO-8400 at escalating dose levels

Experimental group

Description:

IMO-8400 at escalating dose levels by subcutaneous injection

Treatment:

Drug: IMO-8400