Waldenstrom's MacroglobulinemiaPhase 1/28400-401NCT02092909

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

A Phase 1/2 study testing IMO-8400 in people with Waldenstrom's Macroglobulinemia, run by Idera Pharmaceuticals, Inc. at 10 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Waldenstrom's Macroglobulinemia
What is being tested?: IMO-8400
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 31 participants
Where: 10 sitesUnited States
Study dates: Mar 2014to Nov 2017
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients must have a diagnosis of relapsed Waldenstrom's Macroglobulinemia.
In addition to the above, key inclusion and exclusion criteria are listed below.
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

Who cannot join

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

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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.

Trial locations and contacts

10 sites in 1 country.

City, postcode or hospital

10 sites in 1 country

United States10 sites

Emory Winship Cancer Institute
Atlanta, Georgia, 30322
Cancer Centers of Excellence
Fayetteville, Arkansas, 72758
Hackensack University
Hackensack, New Jersey, 07601
MD Anderson Cancer Center
Houston, Texas, 77030
Mayo Clinic Jacksonville
Jacksonville, Florida, 32224
Horizon BioAdvance
Lafayette, Indiana, 47905
UCLA
Los Angeles, California, 90404
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Mayo Clinic
Rochester, Minnesota, 55902
Seattle Cancer Care Alliance
Seattle, Washington, 98109

Other trials in United States

About this study

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

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.

Read the detailed description

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

Conditions: Waldenstrom's Macroglobulinemia
Being tested: IMO-8400
Medical subject headings: Waldenstrom Macroglobulinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT02092909
Study group	Role	What they receive
IMO-8400 at escalating dose levels	Experimental	IMO-8400 at escalating dose levels by subcutaneous injection Receives: Drug: IMO-8400

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: Up to 24 weeks

Secondary outcomes (4)

Best Overall Response
Best Overall Response using criteria from the VIth International Workshop in Waldenstrom's Macroglobulinemia
Measured: Up to 24 weeks
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
Measured: 28 days
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.
Measured: 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)
Pharmacokinetics of escalating dose levels of IMO 8400 administered by SC injection - AUC0-t (hr*ng/mL) .
Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2014Nov 2017

First posted20 Mar 2014 (estimated)
Study startMar 2014
Primary completionApr 2017
Study completionNov 2017

Why it stopped: Lack of efficacy

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Waldenstrom's MacroglobulinemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02092909
Sponsor's protocol ID: 8400-401
Acronym: 8400-401
Status last verified: Aug 2019
First submitted: 18 Mar 2014
Last updated: 10 Sep 2019
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 2
Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
Lymphoplasmacytic Lymphoma, Waldenstrom Macroglobulinemia
Active, not recruitingPhase 2
A Study to Investigate Efficacy and Safety of BCL2 Inhibitor Sonrotoclax as Monotherapy and in Combination With Zanubrutinib in Adults With Waldenström Macroglobulinemia
Waldenstrom Macroglobulinemia, Waldenstrom's Macroglobulinemia Recurrent
Active, not recruitingPhase 2
Bendamustine, Rituximab and Acalabrutinib in Waldenstrom's Macroglobulinemia
Waldenstrom Macroglobulinemia
Not yet recruitingPhase 2
Teclistamab In Waldenstrom's Macroglobulinemia
Waldenstrom's Macroglobulinemia
Not yet recruitingPhase 3
Evaluation of Iopofosine I 131 vs. R-CD in WM Patients
Waldenstrom Macroglobulinaemia, Waldenstrom Macroglobulinemia

All Waldenstrom's Macroglobulinemia trials

Study at a glance

From the registry record, last updated by the sponsor on 10 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02092909
Acronym / sponsor ID: 8400-401 / 8400-401
Conditions: Waldenstrom's Macroglobulinemia
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Lack of efficacy
Enrolment: 31 participants (actual)
Lead sponsor: Idera Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
Study start: Mar 2014
Primary completion: Apr 2017 (actual)
Study completion: Nov 2017 (actual)
First posted: 20 Mar 2014 (estimated)
Results: Posted 29 Aug 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
IMO-8400 at escalating dose levels	Experimental	Drug: IMO-8400IMO-8400 at escalating dose levels by subcutaneous injection

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Patients must have a diagnosis of relapsed Waldenstrom's Macroglobulinemia.
In addition to the above, key inclusion and exclusion criteria are listed below.
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

Key exclusion criteria (11 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
IMO-8400IMO-8400 at escalating dose levels by subcutaneous injection	Drug	IMO-8400 at escalating dose levels

Primary outcome

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

4 secondary outcomes

Best Overall Response
Time frame: Up to 24 weeks
Identify the Number of Patients Experiencing DLTs at Each Dose Level
Time frame: 28 days
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 - 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)

Results and safety

Results posted to the registry on 29 Aug 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
IMO-8400 0.6 mg/kg 1x/wk	6	5
IMO-8400 1.2 mg/kg 1x/wk	5	2
IMO-8400 1.2 mg/kg 2x/wk	14	5
IMO-8400 2.4 mg/kg 1x/wk	6	0

Primary outcome: Safety and Tolerability of IMO-8400 in Patients With Waldenstrom's Macroglobulinemia

Time frame: Up to 24 weeks. Count of participants. Unit: Participants

Measure	IMO-8400 0.6 mg/kg 1x/wk n = 6	IMO-8400 1.2 mg/kg 1x/wk n = 5	IMO-8400 1.2 mg/kg 2x/wk n = 14	IMO-8400 2.4 mg/kg 1x/wk n = 6
At Least 1 TEAE	6	5	14	6
At Least 1 Related TEAE	5	2	12	6
At Least 1 Grade >=3 TEAE	1	2	7	3
At Least 1 SAE	0	0	1	2
At Least 1 DLT	0	0	1	0
At Least 1 TEAE Leading to Death	0	0	0	0
At Least 1 TEAE Leading to Premature Treatment DC	0	0	4	2

Population analysed: Safety Population

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: From obtaining informed consent through EOS visit. (up to 24 weeks). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
IMO-8400 0.6 mg/kg 1x/wk	0 of 6 (0%)	6 of 6 (100%)	0 of 6
IMO-8400 1.2 mg/kg 1x/wk	0 of 5 (0%)	5 of 5 (100%)	0 of 5
IMO-8400 1.2 mg/kg 2x/wk	1 of 14 (7.1%)	13 of 14 (92.9%)	0 of 14
IMO-8400 2.4 mg/kg 1x/wk	2 of 6 (33.3%)	6 of 6 (100%)	0 of 6

Limitations and caveats (from the sponsor): Early termination leading to small numbers of subjects analyzed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Waldenstrom's Macroglobulinemia

RecruitingPhase 2
Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
Lymphoplasmacytic Lymphoma, Waldenstrom Macroglobulinemia
Active, not recruitingPhase 2
A Study to Investigate Efficacy and Safety of BCL2 Inhibitor Sonrotoclax as Monotherapy and in Combination With Zanubrutinib in Adults With Waldenström Macroglobulinemia
Waldenstrom Macroglobulinemia, Waldenstrom's Macroglobulinemia Recurrent
Active, not recruitingPhase 2
Bendamustine, Rituximab and Acalabrutinib in Waldenstrom's Macroglobulinemia
Waldenstrom Macroglobulinemia
Not yet recruitingPhase 2
Teclistamab In Waldenstrom's Macroglobulinemia
Waldenstrom's Macroglobulinemia
Not yet recruitingPhase 3
Evaluation of Iopofosine I 131 vs. R-CD in WM Patients
Waldenstrom Macroglobulinaemia, Waldenstrom Macroglobulinemia

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mark Cornfeld, MD, MPH study director

Idera Pharmaceuticals, Inc.

10 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing IMO-8400 in people with Waldenstrom's Macroglobulinemia, run by Idera Pharmaceuticals, Inc. at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 10 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Tolerability of IMO-8400 in Patients With Waldenstrom's Macroglobulinemia (time frame: Up to 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02092909.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2019.