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

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.

Study Overview

• Status: Terminated
• Conditions: Waldenstrom's Macroglobulinemia
• Intervention / Treatment: Drug: IMO-8400

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72758
      • Cancer Centers of Excellence
  • California
    • Los Angeles, California, United States, 90404
      • UCLA
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Winship Cancer Institute
  • Indiana
    • Lafayette, Indiana, United States, 47905
      • Horizon BioAdvance
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IMO-8400 at escalating dose levels; IMO-8400 at escalating dose levels by subcutaneous injection	Drug: IMO-8400; IMO-8400 at escalating dose levels by subcutaneous injection

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response	Best Overall Response using criteria from the VIth International Workshop in Waldenstrom's Macroglobulinemia	Up to 24 weeks
Identify the Number of Patients Experiencing DLTs at Each Dose Level	To identify an appropriate dose of IMO-8400 for further clinical evaluation via evaluation of DLT at each dose level	28 days
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 - Cmax.	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)	Pharmacokinetics of escalating dose levels of IMO 8400 administered by SC injection - AUC0-t (hr*ng/mL) .	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)

Collaborators and Investigators

• Sponsor: Idera Pharmaceuticals, Inc.
• Investigators: Study Director: Mark Cornfeld, MD, MPH, Idera Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): November 1, 2017

Study Registration Dates

• First Submitted: March 18, 2014
• First Submitted That Met QC Criteria: March 18, 2014
• First Posted (Estimate): March 20, 2014

Study Record Updates

• Last Update Posted (Actual): September 10, 2019
• Last Update Submitted That Met QC Criteria: August 28, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Waldenstrom Macroglobulinemia
• Other Study ID Numbers: 8400-401