Brief Title
Phase 1/2 Dose Escalation Study in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia
Official Title
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
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.
Detailed Description
Eligible subjects will be enrolled and assigned to escalating dose cohorts. Treatment will be
administered by subcutaneous injection.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Safety and Tolerability of IMO-8400 in Patients With Waldenstrom's Macroglobulinemia
Secondary Outcome
Best Overall Response
Condition
Waldenstrom's Macroglobulinemia
Intervention
IMO-8400
Study Arms / Comparison Groups
IMO-8400 at escalating dose levels
Description: IMO-8400 at escalating dose levels by subcutaneous injection
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
31
Start Date
March 2014
Completion Date
November 2017
Primary Completion Date
April 2017
Eligibility Criteria
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
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Mark Cornfeld, MD, MPH, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02092909
Organization ID
8400-401
Responsible Party
Sponsor
Study Sponsor
Idera Pharmaceuticals, Inc.
Study Sponsor
Mark Cornfeld, MD, MPH, Study Director, Idera Pharmaceuticals, Inc.
Verification Date
August 2019