Clinical trial NCT01712490: A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma
Official title: A Randomized, Open-label, Phase 3 Trial of A+AVD Versus ABVD as Frontline Therapy in Patients With Advanced Classical Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hodgkin Lymphoma
Keywords: Hodgkin Lymphoma
Hodgkins Lymphoma
Antibody, Monoclonal
Antibody-Drug Conjugate
Antigens, CD-30
Immunotherapy
Lymphoma
Lymphoma, Classical
ECHELON-1
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Seagen Inc.
First posted: 2012-10-23
Enrollment: 1334
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


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.

Primary outcomes:
measure: Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF)
timeFrame: 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 outcomes:
measure: Overall Survival (OS)
timeFrame: Baseline until death (approximately up to 4 years)
measure: Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF
timeFrame: Baseline up to end of randomized regimen (approximately 1 year)
measure: Number of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
timeFrame: Baseline up to 30 days after last dose of study drug (approximately 1 year)
measure: Number of Participants With Abnormal Clinical Laboratory Values
timeFrame: Baseline up to 30 days after last dose of study drug (approximately 1 year)
measure: Event-free Survival (EFS) Per IRF
timeFrame: Baseline until PD or discontinuation of treatment or death, whichever occurs first (approximately up to 4 years)
measure: Disease-free Survival (DFS) Per IRF
timeFrame: From CR until PD or death (approximately up to 4 years)
measure: Overall Response Rate (ORR) Per IRF
timeFrame: Baseline up to end of randomized regimen (approximately 1 year)
measure: Duration of Response (DOR) Per IRF
timeFrame: From first documented response until PD (approximately 4 years)
measure: Duration of Complete Remission (DOCR) Per IRF
timeFrame: From first documentation of CR until PD (approximately 4 years)
measure: Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy
timeFrame: Baseline up to end of frontline therapy (approximately 4 years)
measure: Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy
timeFrame: Baseline up to end of frontline therapy (approximately 4 years)
measure: Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2
timeFrame: Cycle 2 Day 25
measure: A+AVD: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC) and Total Antibody (TAb)
timeFrame: Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
measure: A+AVD: Cmax: Maximum Observed Plasma Concentration for Brentuximab Vedotin Monomethyl Auristatin E (MMAE)
timeFrame: Cycle 1 Day 1 and Cycle 3 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
measure: A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC and TAb
timeFrame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
measure: A+AVD: AUCinf: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin MMAE
timeFrame: Cycle 1 Day 1: pre-dose and at multiple timepoints (up to 48 hours) post-dose
measure: A+AVD: Number of Participants With Antitherapeutic Antibody (ATA) and Neutralizing Antitherapeutic Antibody (nATA) Positive for Brentuximab Vedotin
timeFrame: Baseline up to end of treatment (approximately 1 year)
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
timeFrame: Baseline up to end of treatment (approximately 1 year)
Other outcomes:
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city: Wroclaw
country: Poland
city: Saint-Petersburg
country: Russian Federation
state: Poselok Pesochny
city: Ufa
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state: Republic Of Bashkortostan
city: Kazan
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city: Moscow
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city: Moskva
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city: St.Petersburg
country: Russian Federation
city: Johannesburg
country: South Africa
state: Gauteng
city: Pretoria
country: South Africa
state: Gauteng
city: Amanzimtoti
country: South Africa
state: Kwa Zulu Natal
city: Bloemfontein
country: South Africa
city: Cape Town
country: South Africa
city: Badalona
country: Spain
city: Barcelona
country: Spain
city: Marbella
country: Spain
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country: Spain
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country: Spain
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country: Turkey
city: Istanbul
country: Turkey
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country: Turkey
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state: Cornwall
city: Aberdeen
country: United Kingdom
state: Scotland
city: Glasgow
country: United Kingdom
state: Scotland
city: Sutton
country: United Kingdom
state: Surrey
city: Cardiff
country: United Kingdom
state: Wales
city: Birmingham
country: United Kingdom
city: Canterbury
country: United Kingdom
city: Exeter
country: United Kingdom
city: Inverness
country: United Kingdom
city: Leicester
country: United Kingdom
city: Lincoln
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Norfolk
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city: Northwood
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Oxford
country: United Kingdom
city: Romford
country: United Kingdom
city: Southampton
country: United Kingdom
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Ansell SM, Radford J, Connors JM, Dlugosz-Danecka M, Kim WS, Gallamini A, Ramchandren R, Friedberg JW, Advani R, Hutchings M, Evens AM, Smolewski P, Savage KJ, Bartlett NL, Eom HS, Abramson JS, Dong C, Campana F, Fenton K, Puhlmann M, Straus DJ; ECHELON-1 Study Group. Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2022 Jul 28;387(4):310-320. doi: 10.1056/NEJMoa2206125. Epub 2022 Jul 13.
citation: Evens AM, Connors JM, Younes A, Ansell SM, Kim WS, Radford J, Feldman T, Tuscano J, Savage KJ, Oki Y, Grigg A, Pocock C, Dlugosz-Danecka M, Fenton K, Forero-Torres A, Liu R, Jolin H, Gautam A, Gallamini A. Older patients (aged >/=60 years) with previously untreated advanced-stage classical Hodgkin lymphoma: a detailed analysis from the phase III ECHELON-1 study. Haematologica. 2022 May 1;107(5):1086-1094. doi: 10.3324/haematol.2021.278438.
citation: Straus DJ, Dlugosz-Danecka M, Connors JM, Alekseev S, Illes A, Picardi M, Lech-Maranda E, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Ramchandren R, Zinzani PL, Hutchings M, Munoz J, Lee HJ, Kim WS, Advani R, Ansell SM, Younes A, Gallamini A, Liu R, Little M, Fenton K, Fanale M, Radford J. Brentuximab vedotin with chemotherapy for stage III or IV classical Hodgkin lymphoma (ECHELON-1): 5-year update of an international, open-label, randomised, phase 3 trial. Lancet Haematol. 2021 Jun;8(6):e410-e421. doi: 10.1016/S2352-3026(21)00102-2.
citation: Straus DJ, Dlugosz-Danecka M, Alekseev S, Illes A, Picardi M, Lech-Maranda E, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Ramchandren R, Zinzani PL, Hutchings M, Connors JM, Radford J, Munoz J, Kim WS, Advani R, Ansell SM, Younes A, Miao H, Liu R, Fenton K, Forero-Torres A, Gallamini A. Brentuximab vedotin with chemotherapy for stage III/IV classical Hodgkin lymphoma: 3-year update of the ECHELON-1 study. Blood. 2020 Mar 5;135(10):735-742. doi: 10.1182/blood.2019003127.
citation: Ramchandren R, Advani RH, Ansell SM, Bartlett NL, Chen R, Connors JM, Feldman T, Forero-Torres A, Friedberg JW, Gopal AK, Gordon LI, Kuruvilla J, Savage KJ, Younes A, Engley G, Manley TJ, Fenton K, Straus DJ. Brentuximab Vedotin plus Chemotherapy in North American Subjects with Newly Diagnosed Stage III or IV Hodgkin Lymphoma. Clin Cancer Res. 2019 Mar 15;25(6):1718-1726. doi: 10.1158/1078-0432.CCR-18-2435. Epub 2019 Jan 7.
citation: Connors JM, Jurczak W, Straus DJ, Ansell SM, Kim WS, Gallamini A, Younes A, Alekseev S, Illes A, Picardi M, Lech-Maranda E, Oki Y, Feldman T, Smolewski P, Savage KJ, Bartlett NL, Walewski J, Chen R, Ramchandren R, Zinzani PL, Cunningham D, Rosta A, Josephson NC, Song E, Sachs J, Liu R, Jolin HA, Huebner D, Radford J; ECHELON-1 Study Group. Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma. N Engl J Med. 2018 Jan 25;378(4):331-344. doi: 10.1056/NEJMoa1708984. Epub 2017 Dec 10.
citation: Younes A, Connors JM, Park SI, Fanale M, O'Meara MM, Hunder NN, Huebner D, Ansell SM. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol. 2013 Dec;14(13):1348-56. doi: 10.1016/S1470-2045(13)70501-1. Epub 2013 Nov 15.