A Study to Compare Standard Therapy to Treat Hodgkin Lymphoma to the Use of Two Drugs, Brentuximab Vedotin and Nivolumab
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| ClinicalTrials.gov Identifier: NCT05675410 |
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Recruitment Status :
Recruiting
First Posted : January 9, 2023
Last Update Posted : September 13, 2023
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Sponsor:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
National Cancer Institute (NCI)
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Brief Summary:
This phase III trial compares the effect of adding immunotherapy (brentuximab vedotin and nivolumab) to standard treatment (chemotherapy with or without radiation) to the standard treatment alone in improving survival in patients with stage I and II classical Hodgkin lymphoma. Brentuximab vedotin is in a class of medications called antibody-drug conjugates. It is made of a monoclonal antibody called brentuximab that is linked to a cytotoxic agent called vedotin. Brentuximab attaches to CD30 positive lymphoma cells in a targeted way and delivers vedotin to kill them. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs such as doxorubicin hydrochloride, bleomycin sulfate, vinblastine sulfate, dacarbazine, and procarbazine hydrochloride work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body's immune response. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Adding immunotherapy to the standard treatment of chemotherapy with or without radiation may increase survival and/or fewer short-term or long-term side effects in patients with classical Hodgkin lymphoma compared to the standard treatment alone.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lugano Classification Limited Stage Hodgkin Lymphoma AJCC v8 | Procedure: Biospecimen Collection Biological: Bleomycin Sulfate Drug: Brentuximab Vedotin Procedure: Computed Tomography Drug: Cyclophosphamide Drug: Dacarbazine Drug: Doxorubicin Hydrochloride Drug: Etoposide Drug: Etoposide Phosphate Other: Fludeoxyglucose F-18 Radiation: Involved-site Radiation Therapy Procedure: Magnetic Resonance Imaging Biological: Nivolumab Procedure: Positron Emission Tomography Drug: Prednisolone Drug: Prednisone Drug: Procarbazine Hydrochloride Other: Questionnaire Administration Drug: Vinblastine Sulfate Drug: Vincristine Sulfate | Phase 3 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 1875 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized Phase 3 Interim Response Adapted Trial Comparing Standard Therapy With Immuno-Oncology Therapy for Children and Adults With Newly Diagnosed Stage I and II Classic Hodgkin Lymphoma |
| Actual Study Start Date : | April 28, 2023 |
| Estimated Primary Completion Date : | April 28, 2031 |
| Estimated Study Completion Date : | April 28, 2031 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Arm A (ABVD)
Patients receive ABVD IV for an additional 2 cycles on study. Each cycle lasts 28 days and ABVD is administered on days 1 and 15 of each cycle. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or magnetic resonance imaging (MRI) throughout the trial. Patients may also undergo blood sample collection on trial.
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Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Biological: Bleomycin Sulfate Given IV
Other Names:
Procedure: Computed Tomography Undergo CT and/or PET-CT
Other Names:
Drug: Dacarbazine Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Other: Fludeoxyglucose F-18 Undergo FDG-PET
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI and/or PET-MRI
Other Names:
Procedure: Positron Emission Tomography Undergo FDG-PET, PET, PET-CT, and/or PET-MRI
Other Names:
Other: Questionnaire Administration Ancillary studies Drug: Vinblastine Sulfate Given IV
Other Names:
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Experimental: Arm B (ABVD, brentuximab vedotin, nivolumab)
Patients receive brentuximab vedotin IV and nivolumab IV once during each treatment cycle. Each cycle lasts 21 days. Treatment continues for 4 cycles. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.
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Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Biological: Bleomycin Sulfate Given IV
Other Names:
Drug: Brentuximab Vedotin Given IV
Other Names:
Procedure: Computed Tomography Undergo CT and/or PET-CT
Other Names:
Drug: Dacarbazine Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Other: Fludeoxyglucose F-18 Undergo FDG-PET
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI and/or PET-MRI
Other Names:
Biological: Nivolumab Given IV
Other Names:
Procedure: Positron Emission Tomography Undergo FDG-PET, PET, PET-CT, and/or PET-MRI
Other Names:
Other: Questionnaire Administration Ancillary studies Drug: Vinblastine Sulfate Given IV
Other Names:
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Experimental: Arm C (ABVD, eBEACOPP, ISRT)
Patients receive eBEACOPP regimen (doxorubicin hydrochloride IV on day 1, cyclophosphamide IV on day 1, etoposide or etoposide phosphate IV on days 1-3, prednisone or prednisolone orally [PO] daily for the first 14 days of each treatment cycle, procarbazine hydrochloride PO on days 1-7, bleomycin sulfate IV on day 8, and vincristine sulfate IV) on day 8 of each treatment cycle. Treatment continues for 2 cycles. Each cycle lasts 21 days. Subsequently, patients undergo ISRT. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.
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Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Biological: Bleomycin Sulfate Given IV
Other Names:
Procedure: Computed Tomography Undergo CT and/or PET-CT
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Dacarbazine Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Drug: Etoposide Phosphate Given IV
Other Name: Etopophos Other: Fludeoxyglucose F-18 Undergo FDG-PET
Other Names:
Radiation: Involved-site Radiation Therapy Undergo ISRT
Other Name: ISRT Procedure: Magnetic Resonance Imaging Undergo MRI and/or PET-MRI
Other Names:
Procedure: Positron Emission Tomography Undergo FDG-PET, PET, PET-CT, and/or PET-MRI
Other Names:
Drug: Prednisolone Given PO
Other Names:
Drug: Prednisone Given PO
Other Names:
Drug: Procarbazine Hydrochloride Given PO
Other Names:
Other: Questionnaire Administration Ancillary studies Drug: Vinblastine Sulfate Given IV
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm D (ABVD, brentuximab vedotin, nivolumab, ISRT)
Patients receive brentuximab vedotin IV and nivolumab IV as in arm B followed by ISRT. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.
|
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Biological: Bleomycin Sulfate Given IV
Other Names:
Drug: Brentuximab Vedotin Given IV
Other Names:
Procedure: Computed Tomography Undergo CT and/or PET-CT
Other Names:
Drug: Dacarbazine Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Other: Fludeoxyglucose F-18 Undergo FDG-PET
Other Names:
Radiation: Involved-site Radiation Therapy Undergo ISRT
Other Name: ISRT Procedure: Magnetic Resonance Imaging Undergo MRI and/or PET-MRI
Other Names:
Biological: Nivolumab Given IV
Other Names:
Procedure: Positron Emission Tomography Undergo FDG-PET, PET, PET-CT, and/or PET-MRI
Other Names:
Other: Questionnaire Administration Ancillary studies Drug: Vinblastine Sulfate Given IV
Other Names:
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Experimental: Arm E (ABVD, AVD)
Patients receive AVD regimen (doxorubicin hydrochloride IV, vinblastine IV, and dacarbazine IV) on days 1 and 15 of each treatment cycle. Each cycle lasts 28 days. Treatment continues for 4 cycles. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.
|
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Biological: Bleomycin Sulfate Given IV
Other Names:
Procedure: Computed Tomography Undergo CT and/or PET-CT
Other Names:
Drug: Dacarbazine Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Other: Fludeoxyglucose F-18 Undergo FDG-PET
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI and/or PET-MRI
Other Names:
Procedure: Positron Emission Tomography Undergo FDG-PET, PET, PET-CT, and/or PET-MRI
Other Names:
Other: Questionnaire Administration Ancillary studies Drug: Vinblastine Sulfate Given IV
Other Names:
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Experimental: Arm F (ABVD, brentuximab vedotin, nivolumab)
Patients receive treatment as in arm B. Patients also undergo FDG-PET, PET, PET-CT, PET-MRI, CT, and/or MRI throughout the trial. Patients may also undergo blood sample collection on trial.
|
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Biological: Bleomycin Sulfate Given IV
Other Names:
Drug: Brentuximab Vedotin Given IV
Other Names:
Procedure: Computed Tomography Undergo CT and/or PET-CT
Other Names:
Drug: Dacarbazine Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Other: Fludeoxyglucose F-18 Undergo FDG-PET
Other Names:
Procedure: Magnetic Resonance Imaging Undergo MRI and/or PET-MRI
Other Names:
Biological: Nivolumab Given IV
Other Names:
Procedure: Positron Emission Tomography Undergo FDG-PET, PET, PET-CT, and/or PET-MRI
Other Names:
Other: Questionnaire Administration Ancillary studies Drug: Vinblastine Sulfate Given IV
Other Names:
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Experimental: Arm G (ABVD, eBEACOPP, ISRT)
Patients receive treatment and imaging, and may undergo blood sample collection as in arm C.
|
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Biological: Bleomycin Sulfate Given IV
Other Names:
Procedure: Computed Tomography Undergo CT and/or PET-CT
Other Names:
Drug: Cyclophosphamide Given IV
Other Names:
Drug: Dacarbazine Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Drug: Etoposide Given IV
Other Names:
Drug: Etoposide Phosphate Given IV
Other Name: Etopophos Other: Fludeoxyglucose F-18 Undergo FDG-PET
Other Names:
Radiation: Involved-site Radiation Therapy Undergo ISRT
Other Name: ISRT Procedure: Magnetic Resonance Imaging Undergo MRI and/or PET-MRI
Other Names:
Procedure: Positron Emission Tomography Undergo FDG-PET, PET, PET-CT, and/or PET-MRI
Other Names:
Drug: Prednisolone Given PO
Other Names:
Drug: Prednisone Given PO
Other Names:
Drug: Procarbazine Hydrochloride Given PO
Other Names:
Other: Questionnaire Administration Ancillary studies Drug: Vinblastine Sulfate Given IV
Other Names:
Drug: Vincristine Sulfate Given IV
Other Names:
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Experimental: Arm H (ABVD, brentuximab vedotin, nivolumab, ISRT)
Patients receive treatment and imaging, and may undergo blood sample collection as in arm D.
|
Procedure: Biospecimen Collection
Undergo blood sample collection
Other Names:
Biological: Bleomycin Sulfate Given IV
Other Names:
Drug: Brentuximab Vedotin Given IV
Other Names:
Procedure: Computed Tomography Undergo CT and/or PET-CT
Other Names:
Drug: Dacarbazine Given IV
Other Names:
Drug: Doxorubicin Hydrochloride Given IV
Other Names:
Other: Fludeoxyglucose F-18 Undergo FDG-PET
Other Names:
Radiation: Involved-site Radiation Therapy Undergo ISRT
Other Name: ISRT Procedure: Magnetic Resonance Imaging Undergo MRI and/or PET-MRI
Other Names:
Biological: Nivolumab Given IV
Other Names:
Procedure: Positron Emission Tomography Undergo FDG-PET, PET, PET-CT, and/or PET-MRI
Other Names:
Other: Questionnaire Administration Ancillary studies Drug: Vinblastine Sulfate Given IV
Other Names:
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Primary Outcome Measures :
- Progression-free survival (PFS) in rapid early responder (RER) patients [ Time Frame: Time from randomization to the first event (disease progression, relapse or death), assessed up to 3 years after the randomization of the last patient or when reaching 230 events, whichever comes first ]Will compare PFS of the immunotherapy (IO) therapy to that of the standard therapy in RER patients. PFS curves will be estimated using Kaplan Meier approach. Primary analyses will be based on 1-sided log-rank test comparisons of PFS curves between the 2 randomized arms per intention-to-treat principle.
- PFS in slow-early responder (SER) patients [ Time Frame: Time from randomization to the first event (disease progression, relapse or death), assessed up to 3 years after the randomization of the last patient or when reaching 116 events, whichever comes first ]Will compare PFS of the IO therapy and involved site radiation therapy (ISRT) to that of the standard therapy and ISRT in SER patients. PFS curves will be estimated using Kaplan Meier approach. Primary analyses will be based on 1-sided log-rank test comparisons of PFS curves between the 2 randomized arms per intention-to-treat principle.
Secondary Outcome Measures :
- Overall survival (OS) in RER patients [ Time Frame: Time of randomization to death, assessed up to 12 years after the last enrollment ]Will compare OS in IO therapy to standard therapy in RER patients. OS will be determined by positron emission tomography (PET)/computed tomography (CT) and compared using a 1-sided log-rank test. The analysis will be conducted based on confidence interval (CI) approach at 12 years after the last enrollment. The 12-year OS and corresponding confidence interval will be estimated with Kaplan-Meier method for each study arm.
- OS in SER patients [ Time Frame: Time of randomization to death, assessed up to 12 years after the last enrollment ]Will compare OS in IO therapy and ISRT to standard therapy and ISRT in SER patients. OS will be determined by PET/CT and compared using a 1-sided log-rank test. The analysis will be conducted based on CI approach at 12 years after the last enrollment. The 12-year OS and corresponding confidence interval will be estimated with Kaplan-Meier method for each study arm.
- OS for entire patient population [ Time Frame: At 12 years after the last enrollment ]Comparison will be conducted using 1-sided log-rank tests. The 12-year OS and corresponding CI will be estimated with Kaplan-Meier method.
- PFS for favorable risk patients [ Time Frame: Time from randomization to the first event (disease progression, relapse or death), assessed up to 3 years ]3-year PFS and corresponding confidence interval will be estimated using the Kaplan-Meier approach. Meanwhile, the 3-year PFS will also be compared between the IO therapy and the standard therapy cohorts with the log-rank test.
- PFS for unfavorable risk patients [ Time Frame: Time from randomization to the first event (disease progression, relapse or death), assessed up to 3 years from last enrollment ]3-year PFS and corresponding confidence interval will be estimated using the Kaplan-Meier approach. Meanwhile, the 3-year PFS will also be compared between the IO therapy and the standard therapy cohorts with the log-rank test.
- PFS for entire population [ Time Frame: Time from randomization to the first event (disease progression, relapse or death), assessed up to 3 years from last enrollment ]3-year PFS and corresponding confidence interval will be estimated using the Kaplan-Meier approach. Meanwhile, the 3-year PFS will also be compared between the IO therapy and the standard therapy cohorts with the log-rank test.
- Event-free survival (EFS) [ Time Frame: Time from randomization to the first event (disease progression, relapse, subsequent malignant neoplasms, or death), assessed up to 12 years from last enrollment ]12-year EFS and corresponding confidence interval will be estimated with Kaplan-Meier approach for patients with and without radiation therapy (RT) under each treatment arm (standard chemotherapy and IO therapy). Meanwhile the EFS curves will be compared between patients with and without RT for each of the treatment arm with log-rank test.
- Incidence of adverse events (AEs) [ Time Frame: Assessed up to 12 years from last enrollment ]Will use the American Society of Clinical Oncology and the Society for Immunotherapy of Cancer guidelines to capture immune-related adverse events. Physician-reported treatment related adverse events will be reported for all grades using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Comparison of toxicities with grades greater or equal to 3 will be conducted between the arms using Fisher's exact test. The maximum grade for each toxicity will be recorded for each patient. The averages and confidence intervals for these toxicity frequencies will be provided. Comparison of AEs will also be conducted for physician-reported treatment-related adverse events between RT and non-RT patients.
- Patient reported outcomes (PROs) [ Time Frame: Assessed up to 12 years from last enrollment ]PROs will be assessed using the PRO-CTCAE for patients 17 and older. The pediatric (Ped)-PRO-CTCAE will be used for patients aged 7-17 and the PRO-CTCAE will be used for those 18 and older. the scores for each attribute together with frequency, severity and/or interference will be presented descriptively using summary statistics at each assessment time. Additionally, the worst severity and/or interference over the entire course will be summarized. The changes among main time points will be calculated. Regression models based on longitudinal measurements can be constructed by considering the following covariates besides age groups: baseline demographics, clinical risk factors, and study arms. Comparisons of PRO CTCAE will also be conducted between RT and non-RT patients.
- Patient-reported fatigue [ Time Frame: At baseline, during chemotherapy (cycle 2, day 1), at completion of therapy (time 0 of follow up) and at 1 and 4 years post completion of therapy ]Will be measured by validated short forms from the Patient Reported Outcomes Measurement Information System initiative. Domain scores will be converted to T-scores with an established standard deviation of 10 points with an average score normalized to 50 within the healthy adult population. The minimal clinically important difference (MCID) in these PRO measures has been accepted to be 2-3 points of the standard deviation ([SD] = 10) of the measure. To account for the dual primary PRO outcomes of fatigue, will consider Bonferroni correction family-wise p-value for overall difference evaluation. Primary interests will be differences in T-scores between immunotherapy and chemotherapy arms at 1-year post completion of therapy.
- Patient-reported cognitive deficits [ Time Frame: At baseline, during chemotherapy (cycle 2, day 1), at completion of therapy (time 0 of follow up) and at 1 and 4 years post completion of therapy ]Will be measured by validated short form, Quality of Life in Neurological Disorders initiatives. Domain scores will be converted to T-scores with an established standard deviation of 10 points with an average score normalized to 50 within the healthy adult population. The MCID in these PRO measures has been accepted to be 2-3 points of the standard deviation (SD = 10) of the measure. To account for the dual primary PRO outcomes of cognitive deficits, will consider Bonferroni correction family-wise p-value for overall difference evaluation. Primary interests will be differences in T-scores between immunotherapy and chemotherapy arms at 1-year post completion of therapy.
- Patient-reported health-related quality of life [ Time Frame: At baseline, during chemotherapy (cycle 2, day 1), at completion of therapy (time 0 of follow up) and at 1 and 4 years post completion of therapy ]
- Incidence of self-reported late morbidities [ Time Frame: Assessed up to 12 years from last enrollment ]Will be collected by using validated measures from the St. Jude Life Cohort. The cumulative incidence of late-morbidities (e.g., cardiovascular, pulmonary and endocrine) will be compared between the standard chemotherapy and the IO therapy and among different age groups (7-14; 15-40 and 41-60) with K-sample method. The frequencies of selected organ toxicities will be compared between two treatment arms, among the three age groups and between RT and non-RT with chi-square tests.
- Effect of metabolic tumor burden (MTV) on PFS [ Time Frame: At baseline prior to initiation of therapy ]MTV will be measured at baseline using fludeoxyglucose F-18 (FDG)-PET. The Kaplan-Meier curves of PFS will be compared between the two levels with log-rank tests.
- Effect of total lesion glycolysis (TLG) on PFS [ Time Frame: At baseline prior to initiation of therapy ]TLG will be measured at baseline using FDG-PET. The Kaplan-Meier curves of PFS will be compared between the two levels with log-rank tests.
- Contribution of social determinants of health (SDOH) to initial response to therapy by race/ethnicity [ Time Frame: Assessed post cycle 2 ]
- Contribution of SDOH to PFS by race/ethnicity [ Time Frame: Assessed up to 12 years after last enrollment ]Kaplan-Meier (K-M) curves of PFS will be generated by racial/ethnic groups. The p values for the K-M curve comparison will be provided via log-rank test. Life tables will provide the PFS over the follow-up years. Associations between race/ethnicity and survival outcomes (PFS) will be evaluated with univariable and multivariable Cox proportional hazard models by considering other covariates such as baseline clinical conditions, toxicities and up-front therapy (conventional versus IO). Backward selection will be used to select those factors with p-value < 0.2, which will be included in final multivariable models.
- Contribution of SDOH to OS by race/ethnicity [ Time Frame: Assessed up to 12 years after last enrollment ]Kaplan-Meier curves of OS will be generated by racial/ethnic groups. The p values for the K-M curve comparison will be provided via log-rank test. Life tables will provide the OS over the follow-up years. Associations between race/ethnicity and survival outcomes (OS) will be evaluated with univariable and multivariable Cox proportional hazard models by considering other covariates such as baseline clinical conditions, SDOH, toxicities and up-front therapy (conventional versus IO). Backward selection will be used to select those factors with p-value < 0.2, which will be included in final multivariable models.
Other Outcome Measures:
- PFS comparison between treatment arms for each age group [ Time Frame: At 3 years ]Will be compared between a standard chemotherapy approach and an IO therapy approach stratified by different age groups (ages 5-11 years, 12-21 years, 22-39 years, 40-60 years) with log-rank test. Cox regression model will be constructed to evaluate the treatment effects for different age groups by considering all other significant including baseline demographics and clinical risk factors. The 3-year PFS and corresponding confidence interval for each age group and each treatment arm will be provided with Kaplan-Meier method.
- Concordance and discordance of 5-point score (PS) visual PET assessments [ Time Frame: At baseline, post cycle 2, and at end of systemic therapy ]The concordance and discordance of 5-PS visual PET assessment from rapid central review and local institutional review will be evaluated at each of the timepoints. Will collect and retrospectively review local versus central review concordance rates. For discordant cases, will document the differences in treatments if only local review or only central review were performed
- Association between FDG PET parameters obtained by automated measurements and PFS [ Time Frame: At baseline, post cycle 2, and at the end of therapy ]The association between FDG PET parameters obtained by automated measurements using convolutional neural networks and PFS will be evaluated in this aim. The PET parameters of interest are total MTV and TLG, tumor standardized uptake value change. PET parameters will be obtained based on artificial intelligence (AI) based measurements. The effect of these PET measurements will be evaluated by Cox regression models.
- Agreement between AI derived FDG-PET measurement extraction and physician-based manual quantitative PET measurement [ Time Frame: At baseline, post cycle 2, and at the end of therapy ]Will compare AI derived automated quantitative FDG-PET measurement extraction and physician-based manual quantitative PET measurement with Spearman rank correlation coefficients for each extracted PET metric.
- Incidence of patient reported adverse events and provider adverse event reporting [ Time Frame: Assessed up to 12 years ]Will be collected by PRO-CTCAE and Ped-PRO-CTCAE. The patient reported adverse events will be compared to provider reported adverse events. The descriptive statistics will be reported, and frequencies will be compared with chi-square tests.
- Association between self-reported race/ethnicity and dimensional SDOH [ Time Frame: Assessed up to 12 years ]Will be evaluated by chi-square tests. Will also calculate the area deprivation index (derived from patient-reported address and zip code to census block-group data for patients treated in the United States, and the Canadian Index of Multiple Deprivation for patients treated in Canada) and investigate its association with race/ethnicity and SDOH.
- Post-relapse/post-progression overall survival by race/ethnicity and select SDOH measures [ Time Frame: Assessed up to 12 years ]The K-M curves will be presented together with p-values via log-rank tests across the different race/ethnicity groups for each treatment arm. Cox proportional hazard models to evaluate the relationship between race/ethnicity and post-relapse OS will be constructed.
- Completion rate of PRO and health-related quality of life contact forms [ Time Frame: At 1 year off treatment ]Will be evaluated for the first 450 eligible participants.
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| Ages Eligible for Study: | 5 Years to 60 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patients must be 5 to 60 years of age at the time of enrollment
- Patients with newly diagnosed untreated histologically confirmed classic Hodgkin lymphoma (cHL) (nodular sclerosis, mixed cellularity, lymphocyte-rich, or lymphocyte-depleted, or not otherwise specified [NOS]) with stage I or II disease
- Patients must have bidimensionally measurable disease (at least one lesion with longest diameter >= 1.5 cm)
- Patients must have a whole body or limited whole body PET scan performed within 42 days prior to enrollment. PET-CT is strongly preferred. PET-MRI allowed if intravenous contrast enhanced CT is also obtained
- Pediatric patients (age 5-17 years) must have an upright posteroanterior (PA) chest X-ray (CXR) for assessment of bulky mediastinal disease. Adult patients must have either a CXR or CT chest
- Patients >= 18 years must have a performance status corresponding to Zubrod scores of 0, 1 or 2
- Patients =< 17 years of age must have a Lansky performance score of >= 50
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Pediatric patients (age 5-17 years): A serum creatinine based on age/gender as follows (within 7 days prior to enrollment):
- 2 to < 6 years (age): 0.8 mg/dL (male), 0.8 mg/dL (female)
- 6 to < 10 years (age): 1 mg/dL (male), 1 mg/dL (female)
- 10 to < 13 years (age): 1.2 mg/dL (male), 1.2 mg/dL (female)
- 13 to < 16 years (age): 1.5 mg/dL (male), 1.4 mg/dL (female)
- >= 16 years (age): 1.7 mg/dL (male), 1.4 mg/dL (female) OR a 24 hour urine creatinine clearance >= 50 mL/min/1.73 m^2 (within 7 days prior to enrollment) OR a glomerular filtration rate (GFR) >= 50 mL/min/1.73 m^2 (within 7 days prior to enrollment). GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
- Note: Estimated GFR (eGFR) from serum or plasma creatinine, cystatin C or other estimates are not acceptable for determining eligibility
- For adult patients (age 18 years or older) (within 7 days prior to enrollment): Creatinine clearance >= 30 mL/min, as estimated by the Cockcroft and Gault formula or a 24-hour urine collection. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on actual body weight
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Total bilirubin =< 2 x upper limit of normal (ULN) (within 7 days prior to enrollment)
- Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
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Aspartate aminotransferase (AST) =< 3 x ULN (within 7 days prior to enrollment)
- Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
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Alanine aminotransferase (ALT) =< 3 x ULN (within 7 days prior to enrollment)
- Unless due to Gilbert's disease, lymphomatous involvement of liver or vanishing bile duct syndrome
- Shortening fraction of >= 27% by echocardiogram (ECHO), multigated acquisition scan (MUGA), or functional cardiac imaging scan (within 7 days prior to enrollment) or ejection fraction of >= 50% by radionuclide angiogram, ECHO, MUGA, or cardiac imaging scan (within 7 days prior to enrollment)
- Diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% of predicted value as corrected for hemoglobin by pulmonary function test (PFT) (within 7 days prior to enrollment). If unable to obtain PFTs, the criterion is: a pulse oximetry reading of > 92% on room air
- Known human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Exclusion Criteria:
- Patients with nodular lymphocyte predominant Hodgkin lymphoma
- Patients with a history of active interstitial pneumonitis or interstitial lung disease
- Patients with a diagnosis of inherited or acquired immunodeficiency that is poorly controlled or requiring active medications, such as primary immunodeficiency syndromes or organ transplant recipients
- Patients with any known uncontrolled intercurrent illness that would jeopardize the patient's safety such as infection, autoimmune conditions, cardiac arrhythmias, angina pectoris, and gastrointestinal disorders affecting swallowing and/or absorption of pills
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Patients with a condition requiring systemic treatment with either corticosteroids (defined as equivalent to > 10 mg daily prednisone for patients >= 18 years or > 0.5 mg/kg [up to 10 mg/day] for patients < 18 years) or other immunosuppressive medications within 14 days prior to enrollment
- Note: Replacement therapy such as thyroxine, insulin, or physiologic corticosteroid for adrenal or pituitary insufficiency is not considered a form of systemic treatment. Inhaled or topical steroids, and adrenal replacement doses (=< 10 mg daily for patients >= 18 years or =< 0.5 mg/kg [up to 10 mg/day] prednisone equivalents) are permitted in the absence of active autoimmune disease
- Note: Steroid use for the control of Hodgkin lymphoma symptoms is allowable, but must be discontinued by cycle 1, day 1
- Patients with peripheral neuropathy > grade 1 at the time of enrollment or patients with known Charcot-Marie-Tooth syndrome
- Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
- Administration of prior chemotherapy, radiation, or antibody-based treatment for cHL
- Prior solid organ transplant
- Prior allogeneic stem cell transplantation
- Live vaccine within 30 days prior to planned day 1 of protocol therapy (e.g., measles, mumps, rubella, varicella, yellow fever, rabies, bacillus calmette guerin [BCG], oral polio vaccine, and oral typhoid). Administration of messenger ribonucleic acid (mRNA) vaccines are permitted
- Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test within 28 days prior to enrollment is required for female patients of childbearing potential
- Lactating females who plan to breastfeed their infants starting with the first dose of study therapy and for at least 6 months after the last treatment
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Sexually active patients of reproductive potential who have not agreed to use a highly effective contraceptive method (failure rate of < 1% per year when used consistently and correctly) for the duration of their study drug therapy. Following therapy, patients will be advised to use contraception as per institutional practice or as listed below for investigational agents, whichever is longer
- Men and women of childbearing potential must continue contraception for a period of 6 months after last dose of brentuximab vedotin
- Women of child-bearing potential (WOCBP) must continue contraception for a period of at least 5 months after the last dose of nivolumab
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05675410
Locations
Show 108 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Tara O Henderson | Children's Oncology Group |
| Responsible Party: | National Cancer Institute (NCI) |
| ClinicalTrials.gov Identifier: | NCT05675410 |
| Other Study ID Numbers: |
NCI-2022-10845 NCI-2022-10845 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) AHOD2131 ( Other Identifier: Children's Oncology Group ) AHOD2131 ( Other Identifier: CTEP ) U10CA180886 ( U.S. NIH Grant/Contract ) |
| First Posted: | January 9, 2023 Key Record Dates |
| Last Update Posted: | September 13, 2023 |
| Last Verified: | June 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page |
| URL: | https://grants.nih.gov/policy/sharing.htm |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
|
Lymphoma Hodgkin Disease Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Deoxyglucose Prednisone Prednisolone Methylprednisolone Acetate Methylprednisolone Methylprednisolone Hemisuccinate Prednisolone acetate |
Hydrocortisone Hydrocortisone 17-butyrate 21-propionate Hydrocortisone acetate Hydrocortisone hemisuccinate Cortisone Cyclophosphamide Dacarbazine Doxorubicin Liposomal doxorubicin Nivolumab Etoposide Etoposide phosphate Vincristine Brentuximab Vedotin Bleomycin |