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)
Brief Title
A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Hodgkin Lymphoma
Eligibility Criteria
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 exclusion criteria. The study center will determine if you meet all of the 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 exclusion criteria. The study center will determine if you meet all of the criteria.
Inclusion Criteria
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.
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.
Gender
All
Gender Based
false
Keywords
Hodgkin Lymphoma
Hodgkins Lymphoma
Antibody, Monoclonal
Antibody-Drug Conjugate
Antigens, CD-30
Immunotherapy
Lymphoma
Lymphoma, Classical
ECHELON-1
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01712490
Org Class
Industry
Org Full Name
Takeda
Org Study Id
C25003
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Randomized, Open-label, Phase 3 Trial of A+AVD Versus ABVD as Frontline Therapy in Patients With Advanced Classical Hodgkin Lymphoma
Primary Outcomes
Outcome Description
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.
Outcome Measure
Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF)
Outcome 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)
Secondary Ids
Secondary Id
2011-005450-60
Secondary Id
U1111-1161-4937
Secondary Id
12/LO/1950
Secondary Id
JapicCTI-142491
Secondary Id
REec-2013-0114
Secondary Id
1025002760
Secondary Id
C25003CTID
Secondary Id
2023-506419-16
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Baseline until death (approximately up to 4 years)
Outcome Measure
Overall Survival (OS)
Outcome Description
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.
Outcome Time Frame
Baseline up to end of randomized regimen (approximately 1 year)
Outcome Measure
Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF
Outcome Time Frame
Baseline up to 30 days after last dose of study drug (approximately 1 year)
Outcome Measure
Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Outcome Time Frame
Baseline up to 30 days after last dose of study drug (approximately 1 year)
Outcome Measure
Number of Participants With Abnormal Clinical Laboratory Values
Outcome Description
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.
Outcome Time Frame
Baseline until PD or discontinuation of treatment or death, whichever occurs first (approximately up to 4 years)
Outcome Measure
Event-free Survival (EFS) Per IRF
Outcome Description
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.
Outcome Time Frame
From CR until PD or death (approximately up to 4 years)
Outcome Measure
Disease-free Survival (DFS) Per IRF
Outcome Description
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.
Outcome Time Frame
Baseline up to end of randomized regimen (approximately 1 year)
Outcome Measure
Overall Response Rate (ORR) Per IRF
Outcome Description
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.
Outcome Time Frame
From first documented response until PD (approximately 4 years)
Outcome Measure
Duration of Response (DOR) Per IRF
Outcome Description
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.
Outcome Time Frame
From first documentation of CR until PD (approximately 4 years)
Outcome Measure
Duration of Complete Remission (DOCR) Per IRF
Outcome Description
CR was defined as disappearance of all evidence of disease as determined by an IRF.
Outcome Time Frame
Baseline up to end of frontline therapy (approximately 4 years)
Outcome Measure
Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy
Outcome Description
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.
Outcome Time Frame
Baseline up to end of frontline therapy (approximately 4 years)
Outcome Measure
Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy
Outcome Description
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.
Outcome Time Frame
Cycle 2 Day 25
Outcome Measure
Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2
Outcome Time Frame
Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Outcome Measure
A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb)
Outcome Time Frame
Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Outcome Measure
A+AVD: Cmax: Maximum Observed Plasma Concentration for Brentuximab Vedotin Monomethyl Auristatin E (MMAE)
Outcome Time Frame
Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Outcome Measure
A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC and TAb
Outcome Time Frame
Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
Outcome Measure
A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin MMAE
Outcome Description
The nATA positive was defined as positive ATA with neutralizing activity at any postbaseline visit.
Outcome Time Frame
Baseline up to end of treatment (approximately 1 year)
Outcome Measure
A+AVD: Number of Participants With Antitherapeutic Antibody (ATA) and Neutralizing Antitherapeutic Antibody (nATA) Positive for Brentuximab Vedotin
Outcome Description
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.
Outcome Time Frame
Baseline up to end of treatment (approximately 1 year)
Outcome Measure
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
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ioannis Mantzaris
Investigator Email
IMANTZAR@montefiore.org