Diffuse Large B Cell Lymphoma
Conditions
Keywords
DLBCL, MYD88 L265P, Lymphoma, Diffuse Large B Cell Lymphoma, Idera, IMO 8400
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.
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.
Interventions
DRUGIMO-8400
MO-8400 given subcutaneously twice weekly
Sponsors
Idera Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IMO-8400 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 | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Entered hospice care | 1 |
| Overall Study | Inability to travel to study site | 1 |
| Overall Study | Lack of Efficacy | 4 |
Baseline characteristics
| Characteristic | IMO-8400 |
|---|---|
| Age, Continuous | 67 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 6 |
| other Total, other adverse events | 4 / 6 |
| serious Total, serious adverse events | 1 / 6 |
Outcome results
Primary
Number of Participants With Adverse Events, Injection Site Reactions, and Concomitant Medications
Frequency of adverse events, injection site reactions, and concomitant medications observed
Time frame: Up to 2 years from first patient visit
Population: Safety population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IMO-8400 | Number of Participants With Adverse Events, Injection Site Reactions, and Concomitant Medications | Subjects with TEAEs | 4 Participants |
| IMO-8400 | Number of Participants With Adverse Events, Injection Site Reactions, and Concomitant Medications | Subjects with ISRs | 1 Participants |
| IMO-8400 | Number of Participants With Adverse Events, Injection Site Reactions, and Concomitant Medications | Subjects with Concomitant Medications | 3 Participants |