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

Waldenstrom's Macroglobulinemia Clinical Trial

— 8400-401  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02092909
• Other study ID #: 8400-401
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2014
• Est. completion date: November 2017

Study information

• Verified date: August 2019
• Source: Idera Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• 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.

Related Conditions & MeSH terms

• Waldenstrom Macroglobulinemia
• Waldenstrom's Macroglobulinemia

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Idera Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

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)