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

NCT02092909 | Terminated Phase 1 Results

• 1 other identifier: 8400-401
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Waldenstrom's Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Best Overall Response

  Up to 24 weeks

• Identify the Number of Patients Experiencing DLTs at Each Dose Level

  28 days

• 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)

  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)

Study Arms (1)

IMO-8400 at escalating dose levels

EXPERIMENTAL

IMO-8400 at escalating dose levels by subcutaneous injection

Drug: IMO-8400

Interventions

IMO-8400 DRUG

IMO-8400 at escalating dose levels by subcutaneous injection

IMO-8400 at escalating dose levels

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• At least 18 years of age.
• Agree to use contraception
• Hemoglobin ≥ 7.5 g/dL, - Absolute neutrophil count ≥ 1.0 x 109/L (1000/mm3), - Platelets ≥ 50,000/μL
• Is nursing or pregnant
• Has BMI \> 34.9 kg/m2.
• Has a positive test for human immunodeficiency virus (HIV-1 or -2) hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg).
• Receiving chronic systemic corticosteroid therapy \> 20 mg of prednisone daily.
• Being treated with other anti-cancer therapies (approved or investigational).
• 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
• Has an active infection requiring systemic antibiotics.
• Has had surgery requiring general anesthesia within 4 weeks of starting the study.
• Has autoimmune cytopenia (anemia, thrombocytopenia, leukopenia).
• Has heart failure of Class III or IV.
• Has sensory or motor neuropathy limiting daily activities.

Sponsors & Collaborators

• Idera Pharmaceuticals, Inc.: lead

Study Sites (10)

Cancer Centers of Excellence

Fayetteville, Arkansas, 72758, United States

Location

UCLA

Los Angeles, California, 90404, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

Emory Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Horizon BioAdvance

Lafayette, Indiana, 47905, United States

Location

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Hackensack University

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

bazlitoran

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

Early termination leading to small numbers of subjects analyzed.

Results Point of Contact

• Title: Idera Medical Monitor
• Organization: Idera Pharmaceuticals

clinicaltrials@iderapharma.com

617-679-5500

Study Officials

• Mark Cornfeld, MD, MPH

  Idera Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2014
• First Posted: March 20, 2014
• Study Start: March 1, 2014
• Primary Completion: April 1, 2017
• Study Completion: November 1, 2017
• Last Updated: September 10, 2019
• Results First Posted: August 29, 2019

Record last verified: 2019-08

Locations

US (10)