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OpenTrials
Completed

NCT Number: NCT01712490

A Frontline Therapy Trial in Participants With Advanced Classical Hodgkin Lymphoma

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)

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Kingswood, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Treatment-naïve participants with Ann Arbor Stage III or IV HL.
  • Histologically confirmed classical Hodgkin Lymphoma (HL) according to the current World Health Organization (WHO) classification.
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (<=) 2.
  • Bidimensional measurable disease as documented by radiographic technique per the International Working Group Revised Criteria for Response Assessment for Malignant Lymphoma.

Exclusion criteria

  • Nodular lymphocyte predominant Hodgkin lymphoma.
  • Cerebral/meningeal disease, including signs and symptoms of progressive multifocalleukoencephalopathy (PML).
  • Sensory or motor peripheral neuropathy.
  • Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy within 12 weeks of first study drug dose.
  • Known human immunodeficiency virus (HIV) positive.
  • 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.

Treatment and study plan

Brentuximab Vedotin

Drug

Brentuximab vedotin (ADCETRIS®)1.2 mg/kg by IV infusion on Days 1 and 15 of each 28-day cycle.

Other names: ADCETRIS®, SGN-35

Doxorubicin

Drug

Doxorubicin: 25 mg/m^2 by IV infusion on Days 1 and 15 of each 28-day cycle.

Other names: Adriamycin

Bleomycin

Drug

Bleomycin: 10 units/m^2 by IV infusion on Days 1 and 15 of each 28-day cycle.

Vinblastine

Drug

Vinblastine: 6 mg/m2 will be administered by IV infusion on Days 1 and 15 of each 28-day cycle

Dacarbazine

Drug

Dacarbazine (DTIC): 375 mg/m^2 by IV infusion on Days 1 and 15 of each 28-day cycle.

Other names: DTIC

Primary outcomes

  1. Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF)

    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)

    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 outcomes

  1. Overall Survival (OS)

    Time frame: 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.

  2. Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF

    Time frame: 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.

  3. 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)

  4. Number of Participants With Abnormal Clinical Laboratory Values

    Time frame: Baseline up to 30 days after last dose of study drug (approximately 1 year)

  5. Event-free Survival (EFS) Per IRF

    Time frame: 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.

  6. Disease-free Survival (DFS) Per IRF

    Time frame: 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.

  7. Overall Response Rate (ORR) Per IRF

    Time frame: 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.

  8. Duration of Response (DOR) Per IRF

    Time frame: 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.

  9. Duration of Complete Remission (DOCR) Per IRF

    Time frame: 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.

  10. Percentage of Participants Not in CR Per IRF Who Received Subsequent Radiation After Completion of Frontline Therapy

    Time frame: 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.

  11. Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy

    Time frame: 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.

  12. Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2

    Time frame: 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. A+AVD: Number of Participants With Antitherapeutic Antibody (ATA) and Neutralizing Antitherapeutic Antibody (nATA) Positive for Brentuximab Vedotin

    Time frame: Baseline up to end of treatment (approximately 1 year)

    The nATA positive was defined as positive ATA with neutralizing activity at any postbaseline visit.

  18. 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

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Takeda

Industry

Collaborators

  • Seagen Inc.

Registry information

Official study title

A Randomized, Open-label, Phase 3 Trial of A+AVD Versus ABVD as Frontline Therapy in Patients With Advanced Classical Hodgkin Lymphoma

Important dates

Study start
2012
Primary completion
2017
Study completion
2026
First posted
Oct 23, 2012
Registry last updated
Feb 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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