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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02092909
Recruitment Status : Terminated (Lack of efficacy)
First Posted : March 20, 2014
Results First Posted : August 29, 2019
Last Update Posted : September 10, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Waldenstrom's Macroglobulinemia Drug: IMO-8400 Phase 1 Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : March 2014
Actual Primary Completion Date : April 2017
Actual Study Completion Date : November 2017


Arm Intervention/treatment
Experimental: IMO-8400 at escalating dose levels
IMO-8400 at escalating dose levels by subcutaneous injection
Drug: IMO-8400
IMO-8400 at escalating dose levels by subcutaneous injection




Primary Outcome Measures :
  1. Safety and Tolerability of IMO-8400 in Patients With Waldenstrom's Macroglobulinemia [ Time Frame: Up to 24 weeks ]
    Safety and tolerability of IMO-8400 in patients with Waldenstrom's Macroglobulinemia: Assessment of adverse events


Secondary Outcome Measures :
  1. Best Overall Response [ Time Frame: Up to 24 weeks ]
    Best Overall Response using criteria from the VIth International Workshop in Waldenstrom's Macroglobulinemia

  2. Identify the Number of Patients Experiencing DLTs at Each Dose Level [ Time Frame: 28 days ]
    To identify an appropriate dose of IMO-8400 for further clinical evaluation via evaluation of DLT at each dose level

  3. 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) ]
    Pharmacokinetics of escalating dose levels of IMO 8400 administered by SC injection - Cmax.

  4. 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) ]
    Pharmacokinetics of escalating dose levels of IMO 8400 administered by SC injection - AUC0-t (hr*ng/mL) .



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02092909


Locations
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United States, Arkansas
Cancer Centers of Excellence
Fayetteville, Arkansas, United States, 72758
United States, California
UCLA
Los Angeles, California, United States, 90404
United States, Florida
Mayo Clinic Jacksonville
Jacksonville, Florida, United States, 32224
United States, Georgia
Emory Winship Cancer Institute
Atlanta, Georgia, United States, 30322
United States, Indiana
Horizon BioAdvance
Lafayette, Indiana, United States, 47905
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55902
United States, New Jersey
Hackensack University
Hackensack, New Jersey, United States, 07601
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Idera Pharmaceuticals, Inc.
Investigators
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Study Director: Mark Cornfeld, MD, MPH Idera Pharmaceuticals, Inc.
  Study Documents (Full-Text)

Documents provided by Idera Pharmaceuticals, Inc.:
Study Protocol  [PDF] March 14, 2016
Statistical Analysis Plan  [PDF] April 21, 2017


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Responsible Party: Idera Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02092909    
Other Study ID Numbers: 8400-401
First Posted: March 20, 2014    Key Record Dates
Results First Posted: August 29, 2019
Last Update Posted: September 10, 2019
Last Verified: August 2019
Additional relevant MeSH terms:
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Waldenstrom Macroglobulinemia
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases