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Phase 1/2 Dose Escalation Study in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia (8400-401)

Primary Purpose

Waldenstrom's Macroglobulinemia

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
IMO-8400
Sponsored by
Idera Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Waldenstrom's Macroglobulinemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Cancer Centers of Excellence
  • UCLA
  • Mayo Clinic Jacksonville
  • Emory Winship Cancer Institute
  • Horizon BioAdvance
  • Mayo Clinic
  • Hackensack University
  • Memorial Sloan-Kettering Cancer Center
  • MD Anderson Cancer Center
  • Seattle Cancer Care Alliance

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

IMO-8400 at escalating dose levels

Arm Description

IMO-8400 at escalating dose levels by subcutaneous injection

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Best Overall Response
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
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.
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)
Pharmacokinetics of escalating dose levels of IMO 8400 administered by SC injection - AUC0-t (hr*ng/mL) .

Full Information

First Posted
March 18, 2014
Last Updated
August 28, 2019
Sponsor
Idera Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02092909
Brief Title
Phase 1/2 Dose Escalation Study in Patients With Relapsed or Refractory Waldenstrom's Macroglobulinemia
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Terminated
Why Stopped
Lack of efficacy
Study Start Date
March 2014 (undefined)
Primary Completion Date
April 2017 (Actual)
Study Completion Date
November 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Idera Pharmaceuticals, Inc.

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Waldenstrom's Macroglobulinemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IMO-8400 at escalating dose levels
Arm Type
Experimental
Arm Description
IMO-8400 at escalating dose levels by subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
IMO-8400
Intervention Description
IMO-8400 at escalating dose levels by subcutaneous injection
Primary Outcome Measure Information:
Title
Safety and Tolerability of IMO-8400 in Patients With Waldenstrom's Macroglobulinemia
Description
Safety and tolerability of IMO-8400 in patients with Waldenstrom's Macroglobulinemia: Assessment of adverse events
Time Frame
Up to 24 weeks
Secondary Outcome Measure Information:
Title
Best Overall Response
Description
Best Overall Response using criteria from the VIth International Workshop in Waldenstrom's Macroglobulinemia
Time Frame
Up to 24 weeks
Title
Identify the Number of Patients Experiencing DLTs at Each Dose Level
Description
To identify an appropriate dose of IMO-8400 for further clinical evaluation via evaluation of DLT at each dose level
Time Frame
28 days
Title
Pharmacokinetics of Escalating Dose Levels of IMO 8400 Administered by SC Injection - Cmax.
Description
Pharmacokinetics of escalating dose levels of IMO 8400 administered by SC injection - Cmax.
Time Frame
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)
Title
Pharmacokinetics of Escalating Dose Levels of IMO 8400 Administered by SC Injection - AUC0-t (hr*ng/mL)
Description
Pharmacokinetics of escalating dose levels of IMO 8400 administered by SC injection - AUC0-t (hr*ng/mL) .
Time Frame
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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: 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 Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Cornfeld, MD, MPH
Organizational Affiliation
Idera Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Cancer Centers of Excellence
City
Fayetteville
State/Province
Arkansas
ZIP/Postal Code
72758
Country
United States
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90404
Country
United States
Facility Name
Mayo Clinic Jacksonville
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Facility Name
Emory Winship Cancer Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Horizon BioAdvance
City
Lafayette
State/Province
Indiana
ZIP/Postal Code
47905
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55902
Country
United States
Facility Name
Hackensack University
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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