Recurrent Transformed B-Cell Non-Hodgkin Lymphoma, Refractory Transformed B-Cell Non-Hodgkin Lymphoma
Conditions
Keywords
Non-Hodgkin Lymphoma
Brief summary
This pilot phase II trial studies ibrutinib in treating patients with transformed indolent (a type of cancer that grows slowly) B-cell non-Hodgkin lymphoma that have returned after a period of improvement (relapsed) or do not respond to treatment (refractory). Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes (proteins) needed for cell growth.
Detailed description
OUTLINE: Patients receive ibrutinib orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 5 years.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGIbrutinib
Given PO
Sponsors
Janssen Pharmaceuticals
University of Washington
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 histologically confirmed transformed indolent B-cell non-Hodgkin lymphoma that is relapsed or refractory to at least one line of therapy * Patients must have a computed tomography (CT) (preferred) or magnetic resonance imaging (MRI) scan of the chest, abdomen, and pelvis within 28 days of enrollment * Patients must have measurable disease defined as lesions greater than 1.5 cm that can be accurately measured in two dimensions by CT (preferred), or MRI * Patients must have a positron emission tomography (PET) scan within 56 days of enrollment * Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 * Absolute neutrophil count (ANC) \>= 1000/mm\^3 or \>= 750/mm\^3 in the setting of marrow involvement by disease * Platelets \>= 50,000/mm\^3 or \>= 30,000/mm\^3 in the setting of marrow involvement by disease or splenomegaly due to disease * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 3 x upper limit of normal (ULN) * Total bilirubin =\< 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin * Creatinine clearance (Clcr) \> 25 mL/min * Patients must be anticipated to complete 2 cycles of therapy in the opinion of the treating physician * Women of childbearing potential and men who are sexually active must affirm they are practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials; men must agree to not donate sperm during or after the study; for females, these restrictions apply for 1 month after the last dose of study drug; for males, these restrictions apply for 3 months after the last dose of the study drug * Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[beta-hCG\]) or urine pregnancy test at screening; women who are pregnant or breastfeeding are ineligible for this study * Sign (or their legally-acceptable representatives must sign) an informed consent document in accordance with institutional and federal guidelines indicating that they understand the investigational nature of and procedures required for the study, including biomarkers, and are willing to participate in and comply with the guidelines of the study
Exclusion criteria
* Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection * Major surgery or a wound that has not fully healed within 4 weeks of initiation of therapy * Known central nervous system lymphoma * History of stroke or intracranial hemorrhage within 6 months of screening * Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) * Requires chronic treatment with strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors * Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification * Vaccinated with live, attenuated vaccines within 4 weeks of initiation of therapy * Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk * Patients with other prior malignancies except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, breast or cervical cancer in situ, or other cancer from which the patient has been disease-free for 5 years or greater, unless approved by the protocol sponsor-investigator/lead-sub-investigator * Patients that previously were treated with ibrutinib for \> 7 days * Previous chemotherapy, immunotherapy, biologically targeted therapy, other investigational agent, or radiation therapy within 3 weeks of initiation of ibrutinib therapy or radio-immunotherapy within 12 weeks of initiation of ibrutinib therapy * Prior allogeneic transplant with graft-versus-host disease (GVHD) requiring immunosuppressive therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Response Rate (Combined Complete Response + Partial Response) | Up to 5 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate | >12 months | — |
| Overall Survival | Up to 5 years | — |
| Complete Response Rate | Up to 5 years | — |
| Response Rate Relative to the Underlying B-cell Histology | Up to 5 years | Participants with a histology of follicular lymphoma at diagnosis achieving at least a partial response to treatment. |
| Tolerability of Chronic Ibrutinib Therapy | Up to 5 years | The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be used to classify and grade toxicities. Count of participants who stopped ibrutinib due to toxicities. |
| Progression-free Survival | Time from first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years | Progression-free survival will be calculated using assessments by investigators. Kaplan-Meier methodology will be used to estimate event-free curves and corresponding quartiles (including the median). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Ibrutinib) Patients receive ibrutinib PO QD in the absence of disease progression or unacceptable toxicity.
Ibrutinib: Given PO
Laboratory Biomarker Analysis: Correlative studies | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Treatment (Ibrutinib) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 12 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| 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 | 1 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 14 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 7 / 20 |
Outcome results
Primary
Overall Response Rate (Combined Complete Response + Partial Response)
Time frame: Up to 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Ibrutinib) | Overall Response Rate (Combined Complete Response + Partial Response) | 6 Participants |
Secondary
Complete Response Rate
Time frame: Up to 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Ibrutinib) | Complete Response Rate | 2 Participants |
Secondary
Disease Control Rate
Time frame: >12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Ibrutinib) | Disease Control Rate | 4 Participants |
Secondary
Overall Survival
Time frame: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Ibrutinib) | Overall Survival | 22.4 months |
Secondary
Progression-free Survival
Progression-free survival will be calculated using assessments by investigators. Kaplan-Meier methodology will be used to estimate event-free curves and corresponding quartiles (including the median).
Time frame: Time from first study drug administration to the first occurrence of disease progression or death from any cause, assessed up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Ibrutinib) | Progression-free Survival | 4.1 months |
Secondary
Response Rate Relative to the Underlying B-cell Histology
Participants with a histology of follicular lymphoma at diagnosis achieving at least a partial response to treatment.
Time frame: Up to 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Ibrutinib) | Response Rate Relative to the Underlying B-cell Histology | 4 Participants |
Secondary
Tolerability of Chronic Ibrutinib Therapy
The National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 will be used to classify and grade toxicities. Count of participants who stopped ibrutinib due to toxicities.
Time frame: Up to 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Ibrutinib) | Tolerability of Chronic Ibrutinib Therapy | 1 Participants |