Waldenstrom's Macroglobulinemia Clinical Trial
— 8400-401Official 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
Verified date | August 2019 |
Source | Idera Pharmaceuticals, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 31 |
Est. completion date | November 2017 |
Est. primary completion date | April 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
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. |
Country | Name | City | State |
---|---|---|---|
United States | Emory Winship Cancer Institute | Atlanta | Georgia |
United States | Cancer Centers of Excellence | Fayetteville | Arkansas |
United States | Hackensack University | Hackensack | New Jersey |
United States | MD Anderson Cancer Center | Houston | Texas |
United States | Mayo Clinic Jacksonville | Jacksonville | Florida |
United States | Horizon BioAdvance | Lafayette | Indiana |
United States | UCLA | Los Angeles | California |
United States | Memorial Sloan-Kettering Cancer Center | New York | New York |
United States | Mayo Clinic | Rochester | Minnesota |
United States | Seattle Cancer Care Alliance | Seattle | Washington |
Lead Sponsor | Collaborator |
---|---|
Idera Pharmaceuticals, Inc. |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Best Overall Response | Best Overall Response using criteria from the VIth International Workshop in Waldenstrom's Macroglobulinemia | Up to 24 weeks | |
Secondary | 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 | |
Secondary | 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) | |
Secondary | 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) |
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