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

Overview

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 Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 2017

Detailed Description

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

Interventions

  • Drug: IMO-8400
    • IMO-8400 at escalating dose levels by subcutaneous injection

Arms, Groups and Cohorts

  • Experimental: IMO-8400 at escalating dose levels
    • IMO-8400 at escalating dose levels by subcutaneous injection

Clinical Trial Outcome Measures

Primary Measures

  • Safety and Tolerability of IMO-8400 in Patients With Waldenstrom’s Macroglobulinemia
    • Time Frame: Up to 24 weeks
    • Safety and tolerability of IMO-8400 in patients with Waldenstrom’s Macroglobulinemia: Assessment of adverse events

Secondary Measures

  • Best Overall Response
    • Time Frame: Up to 24 weeks
    • Best Overall Response using criteria from the VIth International Workshop in Waldenstrom’s Macroglobulinemia
  • Identify the Number of Patients Experiencing DLTs at Each Dose Level
    • Time Frame: 28 days
    • To identify an appropriate dose of IMO-8400 for further clinical evaluation via evaluation of DLT at each dose level
  • Pharmacokinetics of Escalating Dose Levels of IMO 8400 Administered by SC Injection – Cmax.
    • Time Frame: Cycle 1 Week 1 Day 1: Samples were obtained pre-dose (within 1 hr prior to injection) and post-dose at 1 hr (+/-5 min), 2 hrs (+/-10 min) and 4 hrs (+/-15 min)
    • Pharmacokinetics of escalating dose levels of IMO 8400 administered by SC injection – Cmax.
  • Pharmacokinetics of Escalating Dose Levels of IMO 8400 Administered by SC Injection – AUC0-t (hr*ng/mL)
    • Time Frame: Cycle 1 Week 1 Day 1: Samples were obtained pre-dose (within 1 hr prior to injection) and post-dose at 1 hr (+/-5 min), 2 hrs (+/-10 min) and 4 hrs (+/-15 min)
    • Pharmacokinetics of escalating dose levels of IMO 8400 administered by SC injection – AUC0-t (hr*ng/mL) .

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Idera Pharmaceuticals, Inc.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Mark Cornfeld, MD, MPH, Study Director, Idera Pharmaceuticals, Inc.

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