Hodgkin Lymphoma (Category), Lymphoma, Nodular Lymphocyte Predominant Hodgkin Lymphoma
Conditions
Brief summary
Phase 2 trial to study the effectiveness of rituximab in treating patients who have lymphocyte-predominant Hodgkin's lymphoma.
Detailed description
This study will evaluate the partial, complete, and overall response rates to rituximab of subjects with lymphocyte-predominant Hodgkin's lymphoma. Subjects will receive rituximab by IV infusion over several hours once a week for 4 weeks, followed by maintenance therapy as repeat course of the same dose and schedule rituximab at 6, 12, and 18 months. This was a single-arm study with multiple treatment periods added by amendment (ie, Secondary Group), with results reported by treatment period. As this was always considered a single-arm study, there was no intent to report the results for the initial treatment period separately as the Initial Group vs the Secondary Group.
Interventions
DRUGRituximab
Rituximab (biosimilar is Zytux) is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of immune system B-cells. Rituximab destroys B-cells and is therefore used to treat diseases which are characterized by excessive numbers of B-cells, overactive B-cells, or dysfunctional B-cells. This includes many lymphomas, leukemias, transplant rejection, and autoimmune disorders.
Sponsors
Genentech, Inc.
Ranjana Advani
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 3 years * Lymphocyte-predominant Hodgkin's disease (LPHD) of B-cell lineage * Biopsy-confirmed expression of CD20 antigen * At least one tumor mass measuring \> 1.0 cm in largest dimension * No evidence of active infection * Subjects at high risk of Hepatitis B virus (HBV) infection should be screened prior to enrollment. * Performance status of 0 to 2 * Absolute neutrophil count (ANC) \> 1500/mL * Platelet count \> 50,000/mL * Serum creatinine (Cr) \< 1.5 x upper limit of normal (ULN) * Alkaline phosphatase \< 2 x ULN, unless related to primary disease * Bilirubin \< 2 x ULN, unless related to primary disease * Aspartate transaminase (AST) and alanine transaminase (ALT) \< 2 x ULN, unless related to primary disease * Subjects must be able to read and sign Institutional Review Board-approved informed consent
Exclusion criteria
* Life expectancy at least 12 weeks * Evidence of other active malignancies other than cured carcinomas in situ of the cervix or basal cell carcinoma of the skin * Active HBV infection or hepatitis. * Serious non-malignant disease (eg, congestive heart failure, or active uncontrolled bacterial, viral, or fungal infections) * Concomitant or treatment within prior 4 weeks with radiotherapy or chemotherapy (within prior 6 weeks for nitrosourea compounds) * Concurrent treatment with prednisone or other systemic steroid medication * Treatment with any investigational drug within 30 days prior to entry into the study * Treatment with any investigational drug within 5 half-lives of that drug prior to entry into the study * Major surgery, other than diagnostic surgery, within 4 weeks * Any other conditions which, in the opinion of the investigator and/or sponsor, would compromise other protocol objectives * Female patients must be of non-childbearing potential or using adequate contraception with a negative pregnancy test at study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | 5 years | PFS, assessed as the number of patients 5 years after treatment who are alive and without a ≥ 50% increase from nadir in the sum of the product of the greatest lesion diameters (SPD) of any previously-identified abnormal node, or appearance of any new lesion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 5 years | OS, assessed as the number of patients 5 years after treatment who are alive |
| Overall Response Rate (ORR) | 4 weeks | Overall response as assessed as Complete Response (CR) + Partial Response (PR) * CR was determined as complete metabolic response (CMR), meaning complete resolution of 18-fluorodeoxyglucose (FDG) uptake within the tumor volume so that it is indistinguishable from surrounding normal tissue. * PR was determined as partial metabolic response (PMR), meaning reduction of greater than 25% in the standardized uptake value (SUV) adjusted for body surface area (SUV-BSA). A reduction in the extent of tumor FDG uptake is not required for PMR. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab 375 mg/m2 Per Week Rituximab 375 mg/m2 per week by IV infusion for 4 consecutive weeks | 39 |
| Total | 39 |
Baseline characteristics
| Characteristic | Rituximab 375 mg/m2 Per Week |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants |
| Age, Continuous | 42.0 years STANDARD_DEVIATION 13 |
| Region of Enrollment United States | 39 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 39 |
| serious Total, serious adverse events | 28 / 39 |
Outcome results
Primary
Progression-free Survival (PFS)
PFS, assessed as the number of patients 5 years after treatment who are alive and without a ≥ 50% increase from nadir in the sum of the product of the greatest lesion diameters (SPD) of any previously-identified abnormal node, or appearance of any new lesion
Time frame: 5 years
Population: This was a single-arm study with multiple treatment periods added by amendment (ie, Secondary Group), with results reported by treatment period. As this was always considered a single-arm study, there was no intent to report the results for the initial treatment period separately as the Initial Group vs the Secondary Group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab 375 mg/m2 Per Week | Progression-free Survival (PFS) | 18 participants |
Secondary
Overall Response Rate (ORR)
Overall response as assessed as Complete Response (CR) + Partial Response (PR) * CR was determined as complete metabolic response (CMR), meaning complete resolution of 18-fluorodeoxyglucose (FDG) uptake within the tumor volume so that it is indistinguishable from surrounding normal tissue. * PR was determined as partial metabolic response (PMR), meaning reduction of greater than 25% in the standardized uptake value (SUV) adjusted for body surface area (SUV-BSA). A reduction in the extent of tumor FDG uptake is not required for PMR.
Time frame: 4 weeks
Population: This was a single-arm study with multiple treatment periods added by amendment (ie, Secondary Group), with results reported by treatment period. As this was always considered a single-arm study, there was no intent to report the results for the initial treatment period separately as the Initial Group vs the Secondary Group.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab 375 mg/m2 Per Week | Overall Response Rate (ORR) | Overall Response (CR+PR) | 100 percentage of participants |
| Rituximab 375 mg/m2 Per Week | Overall Response Rate (ORR) | Complete Response | 67 percentage of participants |
| Rituximab 375 mg/m2 Per Week | Overall Response Rate (ORR) | Partial Response | 33 percentage of participants |
Secondary
Overall Survival (OS)
OS, assessed as the number of patients 5 years after treatment who are alive
Time frame: 5 years
Population: This was a single-arm study with multiple treatment periods added by amendment (ie, Secondary Group), with results reported by treatment period. As this was always considered a single-arm study, there was no intent to report the results for the initial treatment period separately as the Initial Group vs the Secondary Group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab 375 mg/m2 Per Week | Overall Survival (OS) | 36 participants |