B-cell Lymphoma, Marginal Zone Lymphoma
Conditions
Keywords
MZL, NHL, SMZL, NMZL, MALT
Brief summary
Phase 2, open-label, non-randomized, monotherapy study to evaluate the safety and efficacy of ibrutinib in subject with relapsed/refractory Marginal Zone Lymphoma (MZL).
Detailed description
Ibrutinib is a first-in-class, potent, orally administered covalent inhibitor of Bruton's tyrosine kinase (BTK). Inhibition of BTK blocks downstream B-cell receptor (BCR) signaling pathways and thus prevents B-cell proliferation. In vitro, ibrutinib inhibits purified BTK and selected members of the kinase family with 10-fold specificity compared with non-BTK kinases. Phase 1 and 2 studies of ibrutinib in B-cell malignancies demonstrate modest toxicity and significant single agent activity in a variety of B-cell malignancies, including NHL.
Interventions
DRUGibrutinib
Sponsors
Janssen Research & Development, LLC
Pharmacyclics LLC.
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
Key Inclusion criteria: * Histologically documented marginal zone lymphoma including splenic, nodal, and extranodal sub-types; subjects with splenic MZL must have an additional measurable lesion, nodal or extranodal, as described in inclusion criteria 5 * Previously received one or more lines of therapy including at least one CD20-directed regimen (either as monotherapy or as chemoimmunotherapy) with documented failure to achieve at least PR or documented PD after, the most recent systemic treatment regimen * Men and women ≥18 years of age * ECOG performance status of ≤2 * ≥1 measurable lesion site on CT scan (\>1.5 cm in longest dimension). Lesions in anatomical locations (such as extremities or soft tissue lesions) that are not well visualized by CT may be measured by MRI instead. (Subjects with spleen-only disease are considered as not having measurable disease.) * Life expectancy of \>3 months, in the opinion of the investigator Key
Exclusion criteria
* Medically apparent CNS lymphoma or leptomeningeal disease * History of other malignancies except adequately treated non melanoma skin cancer, curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for ≥2 years * History of allogeneic stem-cell (or other organ) transplantation * Any chemotherapy, anticancer antibodies, or other systemic anticancer therapy within 21 days of the first dose of study drug * Any external beam radiation therapy within 6 weeks prior to the first dose of the study drug * Concurrent use of warfarin or other vitamin K antagonists * Concurrent use of a strong CYP3A inhibitor. Subjects who have received a strong CYP3A inhibitor prior to entering the study must have discontinued therapy for at least 5 half lives of the prohibited medication. * Recent infection requiring IV anti-infective treatment that was completed ≤14 days before the first dose of study drug * Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to CTCAE Grade 0 or 1, or to the levels dictated in the eligibility criteria with the exception of alopecia * Inadequate organ function as defined on laboratory tests
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR (Overall Response Rate) | Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months. | ORR is defined as the proportion of subjects who achieved complete response (CR), partial response (PR). Response criteria are as outlined in the International Working Group Criteria for NHL, Cheson (2007), with disease assessments performed by an independent review committee (IRC). Per Cheson: CR is defined as disappearance of all evidence of disease. PR is defined as regression of measurable disease and no new sites. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DOR (Duration of Response) | Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months. | The DOR analyses is performed on the subset of subjects that achieve CR or PR as determined by IRC. DOR is calculated as the duration of time from the date of first response to the date of progression or death due to any cause. |
Countries
Belgium, France, Germany, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ibrutinib Subjects receive a daily dose of 560 mg of ibrutinib capsules | 63 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | PD, Subj non-Compliant,Study Terminated | 42 |
| Overall Study | Physician Decision | 5 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Ibrutinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 36 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black | 6 Participants |
| Race/Ethnicity, Customized Unknown | 3 Participants |
| Race/Ethnicity, Customized White | 53 Participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 17 / 63 |
| other Total, other adverse events | 63 / 63 |
| serious Total, serious adverse events | 29 / 63 |
Outcome results
Primary
ORR (Overall Response Rate)
ORR is defined as the proportion of subjects who achieved complete response (CR), partial response (PR). Response criteria are as outlined in the International Working Group Criteria for NHL, Cheson (2007), with disease assessments performed by an independent review committee (IRC). Per Cheson: CR is defined as disappearance of all evidence of disease. PR is defined as regression of measurable disease and no new sites.
Time frame: Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Single Arm, Intent to Treat Population | ORR (Overall Response Rate) | 46 Percentage of Participants |
Secondary
DOR (Duration of Response)
The DOR analyses is performed on the subset of subjects that achieve CR or PR as determined by IRC. DOR is calculated as the duration of time from the date of first response to the date of progression or death due to any cause.
Time frame: Analysis was conducted with the cutoff date of 02 Nov 2017, with a median follow-up time of 33.1 months.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Single Arm, Intent to Treat Population | DOR (Duration of Response) | NA Months |