This phase II trial evaluates how well AVD (doxorubicin, vinblastine, dacarbazine) in combination with brentuximab vedotin and nivolumab work in treating patients with stage I-II Hodgkin lymphoma. Drugs used in the chemotherapy, such as doxorubicin, vinblastine, dacarbazine, and brentuximab vedotin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, and/or by stopping them from spreading. Targeted agent, such as nivolumab, may interfere with the ability of cancer cells to grow and spread by enhancing the immune system. Giving doxorubicin, vinblastine, dacarbazine, brentuximab vedotin, and nivolumab may improve survival of patients with stage I-II Hodgkin lymphoma.
PRIMARY OBJECTIVE: I. To estimate progression-free survival (PFS) at 3 years in patients with previously untreated stage I or II non-bulky Hodgkin lymphoma (HL) who received doxorubicin, vinblastine, dacarbazine (AVD) plus brentuximab vedotin (BV) induction therapy followed by nivolumab (N)VB consolidation therapy. SECONDARY OBJECTIVES: I. To estimate the overall survival (OS) rate at 3 years in patients with previously untreated stage I or II non-bulky HL who received AVD plus BV induction therapy followed by NVB consolidation therapy. II. To estimate the percentage of patients with untreated stage I or II non-bulky HL who are positron emission tomography (PET) positive versus PET negative after 3 cycles of AVD plus BV induction therapy. III. To estimate PFS and OS at 3 and 5 years separately for patients who are PET negative versus PET positive after 3 cycles of AVD plus BV induction followed by NVB consolidation therapy. IV. To estimate time to progression (TTP) in patients with previously untreated stage I or II non-bulky HL who received AVD plus BV induction therapy followed by NVB consolidation therapy. V. To estimate the overall response rate and the number of patients who convert to complete response (CMR) after NVB in patients with partial response (PMR) at the end of AVD plus BV induction therapy. VI. To estimate the duration of response in patients with previously untreated stage I or II non-bulky Hodgkin's lymphoma who received AVD plus BV induction therapy followed by NVB consolidation therapy. VII. To evaluate the toxicity and tolerability of AVD plus BV induction followed by NVB consolidation therapy as assessed via the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version \[v\]4). EXPLORATORY OBJECTIVES: I. Optional biopsy tissue samples will be collected for future analysis. II. Optional blood sample will be collected for future analysis. III. Cost-benefit analysis of AVD plus BV followed by NVB consolidation, compared to the current standard therapy with adriamycin, bleomycin, vinblastine plus dacarbazine (ABVD) with or without radiation therapy. OUTLINE: Patients receive doxorubicin intravenously (IV) over 3-5 minutes, vinblastine IV over 3-5 minutes, and dacarbazine IV over \>= 30 minutes, and brentuximab vedotin IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients with PET-positive then receive brentuximab vedotin IV over 30 minutes and nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for 4 cycles in the absence of disease progression or unacceptable toxicity. PET-positive patients then receive nivolumab IV over 30 minutes on day 1. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. PET-negative patients receive nivolumab IV over 30 minutes on day 1 starting after AVD and BV treatment. Treatment repeats every 2 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 4 and 8 weeks, every 3 or 6 months for 2 years, and then once a year for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
82
Given IV
Given IV
Given IV
Correlative studies
Given IV
Given IV
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Mayo Clinic in Rochester
Rochester, Minnesota, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, United States
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, United States
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, United States
M D Anderson Cancer Center
Houston, Texas, United States
University of Washington Medical Center - Montlake
Seattle, Washington, United States
Progression free survival
The distribution of progression-free survival time will be estimated using the method of Kaplan-Meier and the efficacy will be determined by the log rank statistic. Overall progression-free survival at 3 years will be reported.
Time frame: From registration, where progression is by computed tomography (CT)-based or positron emission tomography (PET)-CT based criteria, assessed at 3 years
Overall survival
The distribution of overall survival time will be estimated using the method of Kaplan-Meier. Will be estimated in each group.
Time frame: Time from registration to death due to any cause, assessed at 3 and 5 years
The proportion of patients who are positron emission tomography (PET) negative
Will be estimated by the number of patients who are PET negative divided by the total number of evaluable patients.
Time frame: After 3 courses (84 days)
Proportion of patients who are positron emission tomography (PET) positive
Will be estimated by the number of patients who are PET positive divided by the total number of evaluable patients.
Time frame: After 3 courses (84 days)
Progression free survival
Differences between the groups will be assessed by log-rank statistics.
Time frame: From registration, where progression is by CT-based or PET-CT based criteria, assessed at 84 days
Progression free survival
Differences between the groups will be assessed by log-rank statistics.
Time frame: From registration, where progression is by CT-based or PET-CT based criteria, assessed at 3 years
Progression free survival
Differences between the groups will be assessed by log-rank statistics.
Time frame: From registration, where progression is by CT-based or PET-CT based criteria, assessed at 5 years
Overall response rate (ORR)
The ORR will be estimated by the number of patients with an complete response (CR)/complete metabolic response/partial response (PR)/partial metabolic response or better divided by the total number of evaluable patients. The ORR may be analysed when all patients are off treatment. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.
Time frame: Up to 5 years
Time to progression
The distribution of time to progression will be estimated using the method of Kaplan-Meier.
Time frame: Time from registration to the earliest date of documentation of disease progression, assessed up to 5 years
The proportion of patients who convert from partial response at the end of induction therapy to complete response after brentuximab vedotin plus nivolumab (NVB)
Will be estimated by the number of patients who convert divided by the total number of evaluable patients who receive at least one dose of NVB induction therapy. Exact binomial 95% confidence intervals for the true conversion rate will be calculated.
Time frame: Up to 5 years
Duration of response
Will be defined for all evaluable patients who have achieved a PR or CR as the date at which the patient's objective status is first noted to be a response to the earliest date progression is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier.
Time frame: Up to 5 years
Incidence of adverse events
Will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
Time frame: Up to 5 years
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