Hodgkin Lymphoma
Conditions
Keywords
Hodgkin Lymphoma, Hodgkins Lymphoma, Antibody, Monoclonal, Antibody-Drug Conjugate, Antigens, CD-30, Immunotherapy, Lymphoma, Lymphoma, Classical, ECHELON-1
Brief summary
This open-label, randomized, 2-arm, multicenter, phase 3 study has the primary objective of comparing the modified progression-free survival (mPFS) obtained with brentuximab vedotin (ADCETRIS®) plus AVD (doxorubicin \[Adriamycin\], vinblastine, and dacarbazine; abbreviated A+AVD) versus that obtained with ABVD (doxorubicin \[Adriamycin\],bleomycin, vinblastine, and dacarbazine) for the frontline treatment of advanced classical Hodgkin lymphoma(HL)
Interventions
DRUGbrentuximab vedotin
Brentuximab vedotin (ADCETRIS®)1.2 mg/kg by IV infusion on Days 1 and 15 of each 28-day cycle.
DRUGdoxorubicin
Doxorubicin: 25 mg/m\^2 by IV infusion on Days 1 and 15 of each 28-day cycle.
DRUGbleomycin
Bleomycin: 10 units/m\^2 by IV infusion on Days 1 and 15 of each 28-day cycle.
DRUGvinblastine
Vinblastine: 6 mg/m2 will be administered by IV infusion on Days 1 and 15 of each 28-day cycle
DRUGdacarbazine
Dacarbazine (DTIC): 375 mg/m\^2 by IV infusion on Days 1 and 15 of each 28-day cycle.
Sponsors
Takeda
Seagen Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Treatment-naïve participants with Ann Arbor Stage III or IV HL. 2. Histologically confirmed classical Hodgkin Lymphoma (HL) according to the current World Health Organization (WHO) classification. 3. Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (\<=) 2. 4. Bidimensional measurable disease as documented by radiographic technique per the International Working Group Revised Criteria for Response Assessment for Malignant Lymphoma.
Exclusion criteria
1. Nodular lymphocyte predominant Hodgkin lymphoma. 2. Cerebral/meningeal disease, including signs and symptoms of progressive multifocalleukoencephalopathy (PML). 3. Sensory or motor peripheral neuropathy. 4. Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy within 12 weeks of first study drug dose. 5. Known human immunodeficiency virus (HIV) positive. 6. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection. Please note that there are additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF) | Baseline until PD or death or receipt of any subsequent anticancer therapy for HL after completion of frontline therapy (approximately up to 4 years) | mPFS was defined as the time from the date of randomization to the date of the first of documentation of progressive disease (PD), death due to any cause, or for participants who were confirmed non complete responders per IRF, receipt of subsequent anticancer therapy for Hodgkin lymphoma (HL) after completion of frontline therapy. PD was defined as any new lesion or increase by greater than or equal to (\>=) 50 percent (%) of previously involved sites from nadir. Frontline therapy is the part of standard set of treatments. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Baseline until death (approximately up to 4 years) | OS was defined as the time from the date of randomization to the date of death. Participants without documented death at the time of analysis were censored at the date last known to be alive. |
| Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF | Baseline up to end of randomized regimen (approximately 1 year) | CR rate at the end of randomized regimen per investigator was defined as the percentage of participants who achieved CR at the end of treatment with randomized regimen (ABVD or A+AVD) as determined by IRF. CR was defined as disappearance of all evidence of disease. |
| Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | Baseline up to 30 days after last dose of study drug (approximately 1 year) | — |
| Number of Participants With Abnormal Clinical Laboratory Values | Baseline up to 30 days after last dose of study drug (approximately 1 year) | — |
| Event-free Survival (EFS) Per IRF | Baseline until PD or discontinuation of treatment or death, whichever occurs first (approximately up to 4 years) | EFS was defined as the time from randomization until any cause of treatment failure: PD, premature discontinuation of randomized treatment for any reason, or death due to any cause, whichever occurs first. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir per IRF. |
| Disease-free Survival (DFS) Per IRF | From CR until PD or death (approximately up to 4 years) | DFS per IRF was defined as the time from CR to disease progression as determined by an IRF or to death from lymphoma or acute toxicity from treatment. CR was defined as disappearance of all evidence of disease. |
| Overall Response Rate (ORR) Per IRF | Baseline up to end of randomized regimen (approximately 1 year) | ORR per IRF was defined as the percentage of participants who achieved CR or partial remission (PR) at the end of treatment with randomized regimen (ABVD or A+AVD) as determined by an IRF. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites. |
| Duration of Response (DOR) Per IRF | From first documented response until PD (approximately 4 years) | DOR per IRF in participants with response was the time between first documentation of response (PR or CR) and PD as determined by an IRF. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites. |
| Duration of Complete Remission (DOCR) Per IRF | From first documentation of CR until PD (approximately 4 years) | DOCR per IRF in participants with CR was the time between first documentation of CR and PD as determined by an IRF. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir. CR was defined as disappearance of all evidence of disease. |
| Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy | Baseline up to end of frontline therapy (approximately 4 years) | CR was defined as disappearance of all evidence of disease as determined by an IRF. |
| Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy | Baseline up to end of frontline therapy (approximately 4 years) | CR rate at the end of frontline therapy per IRF was defined as the percentage of participants who achieved CR at the end of frontline therapy that is after completion of either randomized regimen or alternate frontline therapy as determined by an IRF. CR was defined as disappearance of all evidence of disease. |
| Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2 | Cycle 2 Day 25 | PET negativity rate at Cycle 2 was defined as the percentage of participants with negative Cycle 2 PET results defined as Deauville score less than or equal to (\<=) 3 at Cycle 2. The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans. |
| A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb) | Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose | — |
| A+AVD: Cmax: Maximum Observed Plasma Concentration for Brentuximab Vedotin Monomethyl Auristatin E (MMAE) | Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose | — |
| A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC and TAb | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose | — |
| A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin MMAE | Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose | — |
| A+AVD: Number of Participants With Antitherapeutic Antibody (ATA) and Neutralizing Antitherapeutic Antibody (nATA) Positive for Brentuximab Vedotin | Baseline up to end of treatment (approximately 1 year) | The nATA positive was defined as positive ATA with neutralizing activity at any postbaseline visit. |
| Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT | Baseline up to end of treatment (approximately 1 year) | EORTC QLQ-C30 included 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and global health status/QOL scale. It has 28 questions (4-point scale where 1=not at all \[best\] to 4=Very Much \[worst\]) and 2 questions (7-point scale where 1=very poor \[worst\] to 7= excellent \[best\]). Raw scores were converted into scale scores from 0 to 100. For functional scales and global health status/QOL scale, higher scores show better QOL; for symptom scales, lower scores show better QOL. mPFS was time from date of randomization to date of first of documentation of PD, death due to any cause, or for participants who were confirmed non complete responders per IRF, receipt of subsequent anticancer therapy for HL after completion of frontline therapy. PD is any new lesion or increase by \>=50% of previously involved sites from nadir. |
Countries
Australia, Belgium, Brazil, Canada, Czechia, Denmark, France, Hong Kong, Hungary, Italy, Japan, Norway, Poland, Russia, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORStudy Director
Takeda
Participant flow
Recruitment details
Participants took part in the study at 218 investigative sites in Asia Pacific, Europe, Latin America, and North America from 09 November 2012 to the primary completion date of 20 April 2017.
Pre-assignment details
Participants with histologically confirmed diagnosis of advanced classical hodgkin lymphoma (cHL) were enrolled to receive: brentuximab vedotin 1.2 mg/kg plus doxorubicin 25 mg/m\^2, vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2 (A+AVD) or doxorubicin 25 mg/m\^2, bleomycin 10 units/m\^2, vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2 (ABVD).
Participants by arm
| Arm | Count |
|---|---|
| A+AVD Brentuximab vedotin 1.2 milligram per kilogram (mg/kg), infusion, intravenously over 30-minutes plus doxorubicin 25 milligram per square meter (mg/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. Brentuximab vedotin was administered within approximately 1 hour after completion of AVD. | 664 |
| ABVD Doxorubicin 25 mg/m\^2, bleomycin 10 units per square meter (units/m\^2), vinblastine 6 mg/m\^2, and dacarbazine 375 mg/m\^2, infusion, intravenously, once on Days 1 and 15 of each 28-day treatment cycle for up to a maximum of 6 cycles. | 670 |
| Total | 1,334 |
Baseline characteristics
| Characteristic | ABVD | Total | A+AVD |
|---|---|---|---|
| Age, Continuous | 40.2 years STANDARD_DEVIATION 16.05 | 39.5 years STANDARD_DEVIATION 15.95 | 38.8 years STANDARD_DEVIATION 15.83 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 55 Participants | 106 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 577 Participants | 1148 Participants | 571 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 38 Participants | 80 Participants | 42 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 57 Participants | 113 Participants | 56 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 45 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 17 Participants | 35 Participants | 18 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 17 Participants | 27 Participants | 10 Participants |
| Race (NIH/OMB) White | 554 Participants | 1114 Participants | 560 Participants |
| Sex: Female, Male Female | 272 Participants | 558 Participants | 286 Participants |
| Sex: Female, Male Male | 398 Participants | 776 Participants | 378 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 9 / 662 | 13 / 659 |
| other Total, other adverse events | 644 / 662 | 632 / 659 |
| serious Total, serious adverse events | 284 / 662 | 178 / 659 |
Outcome results
Primary
Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF)
mPFS was defined as the time from the date of randomization to the date of the first of documentation of progressive disease (PD), death due to any cause, or for participants who were confirmed non complete responders per IRF, receipt of subsequent anticancer therapy for Hodgkin lymphoma (HL) after completion of frontline therapy. PD was defined as any new lesion or increase by greater than or equal to (\>=) 50 percent (%) of previously involved sites from nadir. Frontline therapy is the part of standard set of treatments.
Time frame: Baseline until PD or death or receipt of any subsequent anticancer therapy for HL after completion of frontline therapy (approximately up to 4 years)
Population: The ITT population included all participants randomized to treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A+AVD | Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF) | NA months |
| ABVD | Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF) | NA months |
Comparison: Hazard ratio (A+AVD/ABVD) and 95% confidence interval (CI) are based on a stratified Cox's proportional hazard regression model with stratification factors region and number of International Prognostic Factor Project (IPFP) risk factors at baseline with treatment as the explanatory variable in the model. Hazard ratio less than (\<) 1 favors A+AVD arm.p-value: 0.03595% CI: [0.603, 0.983]Log Rank
Secondary
A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC and TAb
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Population: The PK population included enrolled participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. The iPK population was the subset of PK population. The iPK population where data at specified timepoints was available.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A+AVD | A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC and TAb | Cycle 1 Day 1: ADC | 47.4 day*microgram per milliliter (day*ug/mL) | Standard Deviation 12 |
| A+AVD | A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC and TAb | Cycle 1 Day 1: TAb | 93.0 day*microgram per milliliter (day*ug/mL) | Standard Deviation 25.7 |
Secondary
A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin MMAE
Time frame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Population: The PK population included enrolled participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. The iPK population was the subset of PK population. The iPK population where data at specified timepoints was available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A+AVD | A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin MMAE | 25.3 day*nanogram per milliliter (day*ng/mL) | Standard Deviation 19.2 |
Secondary
A+AVD: Cmax: Maximum Observed Plasma Concentration for Brentuximab Vedotin Monomethyl Auristatin E (MMAE)
Time frame: Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Population: The PK population included enrolled participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. The iPK population was the subset of PK population. The iPK population where data at specified timepoints was available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| A+AVD | A+AVD: Cmax: Maximum Observed Plasma Concentration for Brentuximab Vedotin Monomethyl Auristatin E (MMAE) | Cycle 1 Day 1 | 3.20 nanogram per milliliter (ng/mL) | Standard Deviation 2.99 |
| A+AVD | A+AVD: Cmax: Maximum Observed Plasma Concentration for Brentuximab Vedotin Monomethyl Auristatin E (MMAE) | Cycle 3 Day 1 | 1.36 nanogram per milliliter (ng/mL) | Standard Deviation 0.79 |
Secondary
A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb)
Time frame: Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Population: The pharmacokinetic (PK) population included enrolled participants with sufficient dosing and PK data to reliably estimate PK parameters as determined by a clinical pharmacologist. The intensive PK (iPK) population was the subset of PK population. The iPK population where data at specified timepoints was available.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| A+AVD | A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb) | Cycle 1 Day 1: ADC | 22.9 microgram per milliliter (microgm/mL) | Standard Deviation 6.72 |
| A+AVD | A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb) | Cycle 3 Day 1: ADC | 23.6 microgram per milliliter (microgm/mL) | Standard Deviation 6.81 |
| A+AVD | A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb) | Cycle 1 Day 1: TAb | 22.6 microgram per milliliter (microgm/mL) | Standard Deviation 5.48 |
| A+AVD | A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb) | Cycle 3 Day 1: TAb | 26.4 microgram per milliliter (microgm/mL) | Standard Deviation 6.11 |
Secondary
A+AVD: Number of Participants With Antitherapeutic Antibody (ATA) and Neutralizing Antitherapeutic Antibody (nATA) Positive for Brentuximab Vedotin
The nATA positive was defined as positive ATA with neutralizing activity at any postbaseline visit.
Time frame: Baseline up to end of treatment (approximately 1 year)
Population: The safety population included all enrolled participants who received at least 1 dose of any study drug. The safety population-immunogenicity-evaluable participants where baseline and at least one postbaseline sample was available.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A+AVD | A+AVD: Number of Participants With Antitherapeutic Antibody (ATA) and Neutralizing Antitherapeutic Antibody (nATA) Positive for Brentuximab Vedotin | ATA positive | 109 participants |
| A+AVD | A+AVD: Number of Participants With Antitherapeutic Antibody (ATA) and Neutralizing Antitherapeutic Antibody (nATA) Positive for Brentuximab Vedotin | nATA positive | 12 participants |
Secondary
Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT
EORTC QLQ-C30 included 30 items across 5 functional scales (physical, role, cognitive, emotional, and social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) and global health status/QOL scale. It has 28 questions (4-point scale where 1=not at all \[best\] to 4=Very Much \[worst\]) and 2 questions (7-point scale where 1=very poor \[worst\] to 7= excellent \[best\]). Raw scores were converted into scale scores from 0 to 100. For functional scales and global health status/QOL scale, higher scores show better QOL; for symptom scales, lower scores show better QOL. mPFS was time from date of randomization to date of first of documentation of PD, death due to any cause, or for participants who were confirmed non complete responders per IRF, receipt of subsequent anticancer therapy for HL after completion of frontline therapy. PD is any new lesion or increase by \>=50% of previously involved sites from nadir.
Time frame: Baseline up to end of treatment (approximately 1 year)
Population: The ITT population included all participants randomized to treatment.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A+AVD | Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT | Baseline: With mPFS event | 78.15 units on scale | Standard Deviation 16.527 |
| A+AVD | Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT | Without mPFS event | 79.85 units on scale | Standard Deviation 16.648 |
| A+AVD | Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT | Change at end of treatment: with mPFS event | 2.68 units on scale | Standard Deviation 15.434 |
| A+AVD | Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT | Change at end of treatment: without mPFS event | 3.35 units on scale | Standard Deviation 17.417 |
| ABVD | Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT | Change at end of treatment: without mPFS event | 6.08 units on scale | Standard Deviation 16.141 |
| ABVD | Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT | Baseline: With mPFS event | 76.68 units on scale | Standard Deviation 18.661 |
| ABVD | Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT | Change at end of treatment: with mPFS event | 8.58 units on scale | Standard Deviation 17.848 |
| ABVD | Change From Baseline in Patient-Reported Outcome (PRO) Scores by mPFS Based on European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (EORTC QLQ-C30) at EOT | Without mPFS event | 79.91 units on scale | Standard Deviation 16.218 |
Secondary
Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy
CR rate at the end of frontline therapy per IRF was defined as the percentage of participants who achieved CR at the end of frontline therapy that is after completion of either randomized regimen or alternate frontline therapy as determined by an IRF. CR was defined as disappearance of all evidence of disease.
Time frame: Baseline up to end of frontline therapy (approximately 4 years)
Population: The ITT population included all participants randomized to treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A+AVD | Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy | 73 percentage of participants |
| ABVD | Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy | 71 percentage of participants |
Secondary
Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF
CR rate at the end of randomized regimen per investigator was defined as the percentage of participants who achieved CR at the end of treatment with randomized regimen (ABVD or A+AVD) as determined by IRF. CR was defined as disappearance of all evidence of disease.
Time frame: Baseline up to end of randomized regimen (approximately 1 year)
Population: The ITT population included all participants randomized to treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A+AVD | Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF | 73 percentage of participants |
| ABVD | Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF | 70 percentage of participants |
Secondary
Disease-free Survival (DFS) Per IRF
DFS per IRF was defined as the time from CR to disease progression as determined by an IRF or to death from lymphoma or acute toxicity from treatment. CR was defined as disappearance of all evidence of disease.
Time frame: From CR until PD or death (approximately up to 4 years)
Population: The ITT included all participants randomized to treatment. The ITT population where participants achieved CR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A+AVD | Disease-free Survival (DFS) Per IRF | NA months |
| ABVD | Disease-free Survival (DFS) Per IRF | NA months |
Secondary
Duration of Complete Remission (DOCR) Per IRF
DOCR per IRF in participants with CR was the time between first documentation of CR and PD as determined by an IRF. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir. CR was defined as disappearance of all evidence of disease.
Time frame: From first documentation of CR until PD (approximately 4 years)
Population: The ITT population included all participants randomized to treatment. The ITT population where participants achieved CR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A+AVD | Duration of Complete Remission (DOCR) Per IRF | NA months |
| ABVD | Duration of Complete Remission (DOCR) Per IRF | NA months |
Secondary
Duration of Response (DOR) Per IRF
DOR per IRF in participants with response was the time between first documentation of response (PR or CR) and PD as determined by an IRF. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.
Time frame: From first documented response until PD (approximately 4 years)
Population: The ITT population included all participants randomized to treatment. The ITT population where participants achieved confirmed response of CR or PR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A+AVD | Duration of Response (DOR) Per IRF | NA months |
| ABVD | Duration of Response (DOR) Per IRF | NA months |
Secondary
Event-free Survival (EFS) Per IRF
EFS was defined as the time from randomization until any cause of treatment failure: PD, premature discontinuation of randomized treatment for any reason, or death due to any cause, whichever occurs first. PD was defined as any new lesion or increase by \>=50% of previously involved sites from nadir per IRF.
Time frame: Baseline until PD or discontinuation of treatment or death, whichever occurs first (approximately up to 4 years)
Population: The ITT population included all participants randomized to treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A+AVD | Event-free Survival (EFS) Per IRF | NA months |
| ABVD | Event-free Survival (EFS) Per IRF | NA months |
Secondary
Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Time frame: Baseline up to 30 days after last dose of study drug (approximately 1 year)
Population: The safety population included all enrolled participants who received at least 1 dose of any study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| A+AVD | Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | TEAE | 653 participants |
| A+AVD | Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | SAE | 284 participants |
| ABVD | Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | TEAE | 646 participants |
| ABVD | Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) | SAE | 178 participants |
Secondary
Number of Participants With Abnormal Clinical Laboratory Values
Time frame: Baseline up to 30 days after last dose of study drug (approximately 1 year)
Population: The safety population included all enrolled participants who received at least 1 dose of any study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A+AVD | Number of Participants With Abnormal Clinical Laboratory Values | 662 participants |
| ABVD | Number of Participants With Abnormal Clinical Laboratory Values | 658 participants |
Secondary
Overall Response Rate (ORR) Per IRF
ORR per IRF was defined as the percentage of participants who achieved CR or partial remission (PR) at the end of treatment with randomized regimen (ABVD or A+AVD) as determined by an IRF. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.
Time frame: Baseline up to end of randomized regimen (approximately 1 year)
Population: The ITT population included all participants randomized to treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A+AVD | Overall Response Rate (ORR) Per IRF | 86 percentage of participants |
| ABVD | Overall Response Rate (ORR) Per IRF | 83 percentage of participants |
Secondary
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death. Participants without documented death at the time of analysis were censored at the date last known to be alive.
Time frame: Baseline until death (approximately up to 4 years)
Population: The ITT population included all participants randomized to treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| A+AVD | Overall Survival (OS) | NA months |
| ABVD | Overall Survival (OS) | NA months |
Comparison: Hazard ratio (A+AVD/ABVD) and 95% CI are based on a stratified Cox's proportional hazard regression model with stratification factors region and number of IPFP risk factors at baseline with treatment as the explanatory variable in the model. Hazard ratio \<1 favors A+AVD arm.p-value: 0.19995% CI: [0.448, 1.184]Log Rank
Secondary
Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy
CR was defined as disappearance of all evidence of disease as determined by an IRF.
Time frame: Baseline up to end of frontline therapy (approximately 4 years)
Population: The ITT population included all participants randomized to treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A+AVD | Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy | 8 percentage of participants |
| ABVD | Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy | 13 percentage of participants |
Secondary
Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2
PET negativity rate at Cycle 2 was defined as the percentage of participants with negative Cycle 2 PET results defined as Deauville score less than or equal to (\<=) 3 at Cycle 2. The Deauville score according to IRF assessment of response was used to evaluate the results of PET scans.
Time frame: Cycle 2 Day 25
Population: The ITT population included all participants randomized to treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A+AVD | Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2 | 89 percentage of participants |
| ABVD | Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2 | 86 percentage of participants |