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

Phase 1

Terminated

• Conditions: Waldenstrom's Macroglobulinemia
• Interventions: Drug: IMO-8400

• Registration Number: NCT02092909
• Lead Sponsor: Idera Pharmaceuticals, Inc.

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 Timeline

• Study Start: 2014-03
• Study First Submitted: 2014-03-18
• Study First Submitted QC: 2014-03-18
• Study First Posted: 2014-03-20
• Primary Completion: 2017-04
• Study Completion: 2017-11
• Results First Submitted: 2018-03-22
• Status Verified: 2019-08
• Results First Submitted QC: 2019-08-28
• Last Update Submitted: 2019-08-28
• Results First Posted: 2019-08-29
• Last Update Posted: 2019-09-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 31

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
IMO-8400 at escalating dose levels	IMO-8400	IMO-8400 at escalating dose levels by subcutaneous injection

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (10)

UCLA; 🇺🇸 Los Angeles, California, United States

Emory Winship Cancer Institute; 🇺🇸 Atlanta, Georgia, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Horizon BioAdvance; 🇺🇸 Lafayette, Indiana, United States

Cancer Centers of Excellence; 🇺🇸 Fayetteville, Arkansas, United States

Hackensack University; 🇺🇸 Hackensack, New Jersey, United States

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Mayo Clinic Jacksonville; 🇺🇸 Jacksonville, Florida, United States