Hodgkin Lymphoma
Conditions
Keywords
non-bulky, limited stage
Brief summary
Brentuximab is an antibody-drug conjugate (ADC), which is the combination of an antibody (a protein that binds to cells) and a chemotherapy molecule. Brentuximab works by using the antibody portion to enter into the Hodgkin lymphoma cells and then releasing the chemotherapy portion, which attempts to destroy the cell. The intravenous chemotherapy drugs Adriamycin, Vinblastine and Dacarbazine (AVD) which you will receive in this research study are approved for use in people with Hodgkin Lymphoma. A drug called bleomycin is usually included with AVD, but since it appears to be a less effective drug with significant potential risks, it is being replaced in this study with the drug brentuximab. In this research study, the investigators are looking to see whether brentuximab in combination with AVD is effective in treating limited-stage Hodgkin Lymphoma.
Detailed description
Each treatment cycle is 28 days. You will receive brentuximab alone on Day 1 and 15 of the first cycle (lead-in cycle). After cycle 1, you will receive brentuximab combined with AVD on Day 1 and 15 for 4-6 cycles, depending on your response to therapy. Brentuximab and AVD will be given to you by intravenous infusion (IV). The following test and procedures will be performed on Days 1 and 15 of each cycle: * Review of any side effects you have experienced and all medications you are taking * Performance Status * Physical exam and vital signs * Routine blood tests * Questionnaire to evaluate symptoms of neuropathy * Research blood sample to look at markers to see how your body is responding to study medication * PET-CT scan prior to completing cycle 2 of combination brentuximab/AVD After the final dose of the study drug: The following assessments will be performed within one month of your last dose of study medication: * Review of any side effects you have experienced and all medications you are taking * Performance Status * Physical exam and vital signs * Routine blood tests * Questionnaire to evaluate symptoms of neuropathy * Research blood sample to look at markers to see how your body is responding to study medication * PET-CT scan Follow up will include the following * Review of any side effects you have experienced and all medications you are taking * Performance Status * Review and Physical exam * Routine blood tests * Questionnaire to evaluate symptoms of neuropathy * CT scans
Interventions
DRUGBrentuximab Vedotin
2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg
DRUGAdriamycin, vinblastine, and dacarbazine
Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine
Sponsors
Beth Israel Deaconess Medical Center
Dana-Farber Cancer Institute
H. Lee Moffitt Cancer Center and Research Institute
Seagen Inc.
Massachusetts General Hospital
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
* Previously untreated stage IA, IB, IIA or IIB classical Hodgkin Lymphoma * Non-bulky disease defined as less than 10 cm in maximal diameter * Measurable disease greater than or equal to 1.5 cm * ECOG performance status of 0 or 2 * Willing to use 2 effective forms of birth control
Exclusion criteria
* No prior chemotherapy or radiotherapy for Hodgkin lymphoma * Not receiving any other investigational agents * No history of allergic reactions attributed to compounds of similar chemical or biologic composition to Adriamycin, Vinblastine, Dacarbazine or brentuximab * No pre-existing grade 3 or greater neuropathy * No uncontrolled intercurrent illness * Not pregnant or breastfeeding * No history of a different malignancy unless disease free for at least one year
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Rate | End of Therapy (median duration of four months) | Complete response rate at the end of therapy as measured by Positron emission tomography-computed tomography (PET/CT). Response is evaluated using Revised International Working Group Criteria. Complete response is defined as disappearance of all evidence of disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate After One Cycle of Brentuximab | 28 days | The number of participants achieving a Partial Response (PR) or Complete Response (CR) after one cycle of Brentuximab monotherapy as measured via PET/CT response. Response is evaluated using the Revised International Working Group Criteria. * CR: Disappearance of all evidence of disease * PR: Regression of measurable disease and no new sites |
| Overall Response Rate | End of Therapy (median duration of four months) | The number of participants achieving a Partial Response (PR) or Complete Response (CR) at the end of therapy as measured via PET/CT response. Response is evaluated using the Revised International Working Group Criteria. * CR: Disappearance of all evidence of disease * PR: Regression of measurable disease and no new sites |
| Grade III or IV Adverse Events | 2 years | A summary of the grade 3 or 4 adverse events experienced by participants as determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The data is shown as the number of participants that experienced at least one grade 3 or 4 adverse event for each of the specified toxicities. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm Brentuximab Vedotin in combination with Adriamycin, Vinblastine and Dacarbazine
Brentuximab Vedotin: 2 doses administered 14 days apart; followed by combination therapy with AVD for 4-6 cycles; 1.2 mg/kg
Adriamycin, vinblastine, and dacarbazine: Combination therapy with brentuximab for 4-6 cycles; 25 mg/m2 Adriamycin; 6 mg/m2 Vinblastine; 375 mg/m2 Dacarbazine | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Treatment Arm |
|---|---|
| Age, Continuous | 36 years |
| Age, Customized 20 - 30 years | 10 Participants |
| Age, Customized 31 - 40 years | 9 Participants |
| Age, Customized 41 - 60 years | 10 Participants |
| Age, Customized 61 - 75 years | 5 Participants |
| Cellularity Hypercellular | 1 Participants |
| Cellularity Hypocellular | 4 Participants |
| Cellularity Missing | 19 Participants |
| Cellularity Normocellular | 10 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 8 Participants |
| Histology Classical Hodgkin Lymphoma, NOS | 8 Participants |
| Histology Lymphocytic Rich | 4 Participants |
| Histology Mixed Cellularity | 4 Participants |
| Histology Nodular Sclerosis | 18 Participants |
| Longest Tumor Diameter | 33.4 Centimeters (cm) |
| Number of Lesions | 5 Lesions |
| Race/Ethnicity, Customized More Than One Race | 1 Participants |
| Race/Ethnicity, Customized Other | 7 Participants |
| Race/Ethnicity, Customized White | 26 Participants |
| Region of Enrollment United States | 34 participants |
| Risk Class Early Favorable | 21 Participants |
| Risk Class Early Unfavorable | 13 Participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 17 Participants |
| Stage IA | 6 Participants |
| Stage IIA | 24 Participants |
| Stage IIB | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 34 |
| other Total, other adverse events | 34 / 34 |
| serious Total, serious adverse events | 15 / 34 |
Outcome results
Primary
Complete Response Rate
Complete response rate at the end of therapy as measured by Positron emission tomography-computed tomography (PET/CT). Response is evaluated using Revised International Working Group Criteria. Complete response is defined as disappearance of all evidence of disease.
Time frame: End of Therapy (median duration of four months)
Population: Two participants were not evaluated for response due to a death and a withdrawal.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Arm | Complete Response Rate | 31 Participants |
Secondary
Grade III or IV Adverse Events
A summary of the grade 3 or 4 adverse events experienced by participants as determined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The data is shown as the number of participants that experienced at least one grade 3 or 4 adverse event for each of the specified toxicities.
Time frame: 2 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Arm | Grade III or IV Adverse Events | Peripheral sensory neuropathy | 8 participants |
| Treatment Arm | Grade III or IV Adverse Events | Neutrophil count decreased | 21 participants |
| Treatment Arm | Grade III or IV Adverse Events | Fatigue | 3 participants |
| Treatment Arm | Grade III or IV Adverse Events | Nausea | 1 participants |
| Treatment Arm | Grade III or IV Adverse Events | Anemia | 2 participants |
| Treatment Arm | Grade III or IV Adverse Events | White blood cell decreased | 6 participants |
| Treatment Arm | Grade III or IV Adverse Events | Abdominal pain | 2 participants |
| Treatment Arm | Grade III or IV Adverse Events | Diarrhea | 1 participants |
| Treatment Arm | Grade III or IV Adverse Events | Febrile neutropenia | 12 participants |
| Treatment Arm | Grade III or IV Adverse Events | Vomiting | 1 participants |
| Treatment Arm | Grade III or IV Adverse Events | Mucositis oral | 1 participants |
| Treatment Arm | Grade III or IV Adverse Events | Weight loss | 2 participants |
| Treatment Arm | Grade III or IV Adverse Events | Dehydration | 1 participants |
| Treatment Arm | Grade III or IV Adverse Events | Hypertension | 1 participants |
| Treatment Arm | Grade III or IV Adverse Events | Infections and infestations - Other, specify | 1 participants |
| Treatment Arm | Grade III or IV Adverse Events | Blood and lymphatic system disorders - Other, spec | 1 participants |
Secondary
Overall Response Rate
The number of participants achieving a Partial Response (PR) or Complete Response (CR) at the end of therapy as measured via PET/CT response. Response is evaluated using the Revised International Working Group Criteria. * CR: Disappearance of all evidence of disease * PR: Regression of measurable disease and no new sites
Time frame: End of Therapy (median duration of four months)
Population: Two participants were not evaluated for response due to a death and a withdrawal.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment Arm | Overall Response Rate | Complete Response | 31 Participants |
| Treatment Arm | Overall Response Rate | Partial Response | 0 Participants |
Secondary
Overall Response Rate After One Cycle of Brentuximab
The number of participants achieving a Partial Response (PR) or Complete Response (CR) after one cycle of Brentuximab monotherapy as measured via PET/CT response. Response is evaluated using the Revised International Working Group Criteria. * CR: Disappearance of all evidence of disease * PR: Regression of measurable disease and no new sites
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment Arm | Overall Response Rate After One Cycle of Brentuximab | 18 Participants |