Lymphoma
Conditions
Keywords
stage II adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma, adult lymphocyte depletion Hodgkin lymphoma, adult mixed cellularity Hodgkin lymphoma, adult nodular sclerosis Hodgkin lymphoma
Brief summary
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with newly diagnosed stage II, stage III, or stage IV Hodgkin's lymphoma.
Detailed description
OBJECTIVES: Primary * Investigate plasma DNA biomarkers, including plasma clonal immunoglobulin DNA, tumor suppressor gene methylation, and Epstein-Barr virus DNA, in patients receiving rituximab and doxorubicin hydrochloride, bleomycin, vinblastine, and dacarbazine (ABVD) for newly diagnosed stage II-IV classical Hodgkin's lymphoma. * Characterize the impact of rituximab on these markers. * Characterize the relationship between marker detection and clinical outcome. Secondary * Estimate the event-free survival of patients with newly diagnosed Hodgkin's lymphoma treated with rituximab and ABVD. * Assess the presence of Hodgkin's lymphoma stem cells in peripheral blood mononuclear cells at baseline, after treatment with rituximab, and after treatment with ABVD. * Assess whether plasma DNA biomarkers add information to fludeoxyglucose F 18 positron emission tomography (FDG-PET) in assessing tumor response. OUTLINE: Patients receive doxorubicin hydrochloride IV, vinblastine IV, bleomycin IV, and dacarbazine IV (ABVD) on days 1 and 15 of all courses. Patients also receive rituximab IV on days -6, 1, 8, 15, and 22 of ABVD course 1 and on day 1 only of ABVD courses 2, 4, and 6. Treatment repeats every 28 days for 6-8 courses in the absence of disease progression or unacceptable toxicity. Patients with bulky disease may undergo radiotherapy. Plasma samples are obtained during treatment for investigation of tumor markers (e.g., immunoglobulin rearrangement, patterns of DNA methylation, and the presence of Epstein-Barr virus DNA). Patients undergo fludeoxyglucose F18 positron emission tomography periodically during the study. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study.
Interventions
DRUGBleomycin
BIOLOGICALRituximab
DRUGDacarbazine
DRUGDoxorubicin
DRUGVinblastine
Sponsors
National Cancer Institute (NCI)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed classical Hodgkin's lymphoma * No lymphocyte-predominant histology * Stage II, III, or IV disease * Newly diagnosed disease PATIENT CHARACTERISTICS: * Performance status 0-2 * Creatinine \< 2.0 mg/dL * Bilirubin \< 5 mg/dL * Not pregnant or nursing * No HIV positivity * Hepatitis B surface antigen negative * No active concurrent malignancy except for superficial nonmelanoma skin cancer or cervical carcinoma in situ PRIOR CONCURRENT THERAPY: * No prior chemotherapy or radiotherapy for Hodgkin's lymphoma * Steroids allowed if medically required before chemotherapy initiation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Rituximab on EBV(+) Tumors | Up to 56 months | Number of relapses among participants who had tumors positive for Epstein-Barr virus (EBV). |
| Relationship Between Marker Detection and Clinical Outcome | 3 years | Number of relapses for participants who did and did not have re-emergence of clonal CD27(+) ALDH(+) B cells after completing study intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival | 3 years | Percentage of participants who did not experience death, relapse, or progression (worsening) of their lymphoma. |
| Addition of Information to Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) by Plasma DNA Biomarkers | 5 years | — |
Countries
United States
Participant flow
Pre-assignment details
One subject withdrew consent prior to initiating the study.
Participants by arm
| Arm | Count |
|---|---|
| R-ABVD ABVD (Adriamycin/doxorubicin; vinblastine; bleomycin; dacarbazine) given as standard for 6-8 cycles. Rituximab given 375 mg/m\^2 Cycle 1 Days -6, 1, 8, 15, and 22. Rituximab given 375 mg/m\^2 Cycles 2, 4, and 6 Day 1. | 49 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | R-ABVD |
|---|---|
| Age, Continuous | 33 years |
| Region of Enrollment United States | 49 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 50 |
| other Total, other adverse events | 0 / 50 |
| serious Total, serious adverse events | 16 / 50 |
Outcome results
Primary
Effect of Rituximab on EBV(+) Tumors
Number of relapses among participants who had tumors positive for Epstein-Barr virus (EBV).
Time frame: Up to 56 months
Population: Only 4 participants had EBV(+) tumors.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R-ABVD | Effect of Rituximab on EBV(+) Tumors | 0 relapses |
Primary
Relationship Between Marker Detection and Clinical Outcome
Number of relapses for participants who did and did not have re-emergence of clonal CD27(+) ALDH(+) B cells after completing study intervention.
Time frame: 3 years
Population: Only 21 participants had a detectable CD27(+) ALDH(+) clone prior to study intervention. The remaining participants either did not have such a clone or did not have a sample tested to look for a clone.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| R-ABVD | Relationship Between Marker Detection and Clinical Outcome | No re-emergence of clone | 0 relapses |
| R-ABVD | Relationship Between Marker Detection and Clinical Outcome | Re-emergence of clone | 2 relapses |
Secondary
Addition of Information to Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) by Plasma DNA Biomarkers
Time frame: 5 years
Population: Data pertaining to this outcome was not collected.
Secondary
Event-free Survival
Percentage of participants who did not experience death, relapse, or progression (worsening) of their lymphoma.
Time frame: 3 years
Population: All evaluable participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| R-ABVD | Event-free Survival | 83 percentage of participants |