Dose Escalation Study in Patients With Relapsed or Refractory DLBCL and MyD88 L265P Mutation

• Sponsor: Idera Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02252146
• Collaborator: (none)
• Enrollment: 6
• Locations: 12
• Arm: 1
• Duration (Months): 30
• Patients Per Site: 0.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Recent reports have identified a specific oncogenic mutation L265P of the MYD88 gene in approximately 30% of the patients with the activated B-cell (ABC) type of Diffuse Large B Cell Lymphoma (DLBCL). MYD88 is an initial adapter linker protein in the signaling pathway of the Toll Like Receptors (TLRs), including the endosomal TLRs 7, 8, and 9, for which the ligands are nucleic acids. IMO-8400 is an oligonucleotide specifically designed to inhibit ligand activation of TLRs 7,8, and 9. Recent studies indicate that in the presence of L265P mutation ligand activation of those TLRs results in markedly increased signaling with subsequent increased cell activation, cell survival, and cell proliferation. The scientific rationale for assessing the use of IMO-8400 to treat patients with DLBCL and the L265P mutation is based on laboratory observations that IMO-8400 inhibits ligand-based activation of cells with the mutation and decreases the survival and proliferation of the cell populations responsible for the propagation of the disease.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B Cell Lymphoma	Drug: IMO-8400	Phase 1/Phase 2

Detailed Description

Eligible subjects will be enrolled and assigned to one of five dose cohorts. Treatment will be administered by subcutaneous injection until progression or intolerable toxicity.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Open-label, Multiple-dose, Dose-escalation Study to Evaluate the Safety and Tolerability of IMO-8400 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Presence of the MyD88 L265P Mutation
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Dec 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IMO-8400 IMO-8400 0.3 mg/kg twice weekly, 0.6 mg/kg twice weekly, or 1.2 mg/kg twice weekly	Drug: IMO-8400; MO-8400 given subcutaneously twice weekly

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events, Injection Site Reactions, and Concomitant Medications [Up to 2 years from first patient visit]

   Frequency of adverse events, injection site reactions, and concomitant medications observed

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have a diagnosis of Diffuse Large B Cell Lymphoma (DLBCL) of non-GCB subtype, established according to the World Health Organization (WHO) criteria that has been tested for the MyD88 L265P mutation.

• In addition to the above, key inclusion and exclusion criteria are listed below.

1. Be at least 18 years of age

2. Agree to use contraception

Exclusion Criteria:

1. Is nursing or pregnant

2. DLBCL of GCB subtype

3. Has BMI > 34.9 kg/m2

4. Has a positive test for human immunodeficiency virus (HIV-1 or -2) hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg)

5. Receiving chronic systemic corticosteroid therapy > 20 mg of prednisone daily

6. Being treated with other anti-cancer therapies (approved or investigational)

7. Has an active infection requiring systemic antibiotics

8. Has had surgery requiring general anesthesia within 4 weeks of starting the study

9. Has heart failure of Class III or IV

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Medical Center	Los Angeles	California	United States	90095
2	Emory University	Atlanta	Georgia	United States	30306
3	Cancer Care Specialists of Illinois	Decatur	Illinois	United States	62526
4	Horizon Bio Advance	Lafayette	Indiana	United States	47905
5	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
6	Mayo Clinic	Rochester	Minnesota	United States	55905
7	Washington University	Saint Louis	Missouri	United States	63110
8	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
9	Columbia University Medical Center	New York	New York	United States	10019
10	Cleveland Clinic	Cleveland	Ohio	United States	44109
11	Vanderbilt Ingram Cancer Center	Nashville	Tennessee	United States	37232
12	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Idera Pharmaceuticals, Inc.

Investigators

• Study Director: Mark Cornfeld, MD, MPH, Idera Pharmaceuticals, Inc.

Study Documents (Full-Text)

• Study Protocol - Jan 29, 2016
• Statistical Analysis Plan - Nov 11, 2016

More Information

Publications

None provided.

• Responsible Party: Idera Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02252146
• Other Study ID Numbers: 8400-402
• First Posted: Sep 30, 2014
• Last Update Posted: Dec 12, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by Idera Pharmaceuticals, Inc.: DLBCL; MYD88 L265P; Lymphoma; Diffuse Large B Cell Lymphoma; Idera; IMO 8400
• Additional relevant MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse

Study Results

Participant Flow

Arm/Group Title	IMO-8400
Arm/Group Description	IMO-8400 0.3 mg/kg twice weekly, 0.6 mg/kg twice weekly, or 1.2 mg/kg twice weekly IMO-8400: IMO-8400 given subcutaneously twice weekly
Period Title: Overall Study
STARTED	6
COMPLETED	0
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	IMO-8400
Arm/Group Description	IMO-8400 0.3 mg/kg twice weekly, 0.6 mg/kg twice weekly, or 1.2 mg/kg twice weekly IMO-8400: MO-8400 given subcutaneously twice weekly
Overall Participants	6
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67
Sex: Female, Male (Count of Participants)
Female	4 66.7%
Male	2 33.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 16.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	5 83.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events, Injection Site Reactions, and Concomitant Medications
Description	Frequency of adverse events, injection site reactions, and concomitant medications observed
Time Frame	Up to 2 years from first patient visit

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	IMO-8400
Arm/Group Description	IMO-8400 0.3 mg/kg twice weekly, 0.6 mg/kg twice weekly, or 1.2 mg/kg twice weekly IMO-8400: MO-8400 given subcutaneously twice weekly
Measure Participants	6
Subjects with TEAEs	4 66.7%
Subjects with ISRs	1 16.7%
Subjects with Concomitant Medications	3 50%

Adverse Events

Time Frame	Up to 2 years after start of study treatment
Arm/Group Title	IMO-8400
Arm/Group Description	IMO-8400 0.3 mg/kg twice weekly, 0.6 mg/kg twice weekly, or 1.2 mg/kg twice weekly IMO-8400: MO-8400 given subcutaneously twice weekly
All Cause Mortality
	IMO-8400
	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)
Serious Adverse Events
	IMO-8400
	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)
Gastrointestinal disorders
Abdominal pain	1/6 (16.7%)
Vomiting	1/6 (16.7%)
General disorders
Disease progression	1/6 (16.7%)
Pyrexia	1/6 (16.7%)
Infections and infestations
Sepsis	1/6 (16.7%)
Injury, poisoning and procedural complications
Radiation necrosis	1/6 (16.7%)
Other (Not Including Serious) Adverse Events
	IMO-8400
	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)
Blood and lymphatic system disorders
Anemia	2/6 (33.3%)
Thrombocytopenia	2/6 (33.3%)
Lymphadenopathy	1/6 (16.7%)
Eye disorders
Lacrimation increase	2/6 (33.3%)
Dry eye	1/6 (16.7%)
Eye discharge	1/6 (16.7%)
Eye pain	1/6 (16.7%)
Ocular hyperaemia	1/6 (16.7%)
Gastrointestinal disorders
Nausea	3/6 (50%)
Abdominal pain	2/6 (33.3%)
Vomiting	2/6 (33.3%)
Diarrhoea	1/6 (16.7%)
General disorders
Disease progression	1/6 (16.7%)
Injection site reaction	1/6 (16.7%)
Pyrexia	1/6 (16.7%)
Infections and infestations
Oral herpes	1/6 (16.7%)
Injury, poisoning and procedural complications
Contusion	1/6 (16.7%)
Radiation necrosis	1/6 (16.7%)
Investigations
Neutrophil count decreased	1/6 (16.7%)
Weight decreased	1/6 (16.7%)
White blood cell count decreased	1/6 (16.7%)
Hyperkalaemia	1/6 (16.7%)
Hyponatraemia	1/6 (16.7%)
Metabolism and nutrition disorders
Hypercalcaemia	1/6 (16.7%)
Musculoskeletal and connective tissue disorders
Muscle spasms	1/6 (16.7%)
Neck pain	1/6 (16.7%)
Nervous system disorders
Lethargy	1/6 (16.7%)
Peripheral sensory neuropathy	1/6 (16.7%)
Skin and subcutaneous tissue disorders
Rash erythematous	2/6 (33.3%)
Rash	1/6 (16.7%)
Skin lesion	1/6 (16.7%)
Hypotension	1/6 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.