A Randomized, Open-label, Phase 3 Trial of A+AVD Versus ABVD as Frontline Therapy in Patients With Advanced Classical Hodgkin Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 1,334
- 主要终点
- Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF)
研究概览
简要总结
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 (<=)
- •Bidimensional measurable disease as documented by radiographic technique per the International Working Group Revised Criteria for Response Assessment for Malignant Lymphoma.
排除标准
- •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.
研究组 & 干预措施
A + AVD
A+AVD consists of brentuximab vedotin (ADCETRIS®) 1.2 milligram per kilogram (mg/kg) plus doxorubicin 25 milligram per square meter (mg/m^2), vinblastine 6 mg/m^2, and dacarbazine (DTIC) 375 mg/m^2.
干预措施: brentuximab vedotin (Drug)
A + AVD
A+AVD consists of brentuximab vedotin (ADCETRIS®) 1.2 milligram per kilogram (mg/kg) plus doxorubicin 25 milligram per square meter (mg/m^2), vinblastine 6 mg/m^2, and dacarbazine (DTIC) 375 mg/m^2.
干预措施: doxorubicin (Drug)
A + AVD
A+AVD consists of brentuximab vedotin (ADCETRIS®) 1.2 milligram per kilogram (mg/kg) plus doxorubicin 25 milligram per square meter (mg/m^2), vinblastine 6 mg/m^2, and dacarbazine (DTIC) 375 mg/m^2.
干预措施: vinblastine (Drug)
A + AVD
A+AVD consists of brentuximab vedotin (ADCETRIS®) 1.2 milligram per kilogram (mg/kg) plus doxorubicin 25 milligram per square meter (mg/m^2), vinblastine 6 mg/m^2, and dacarbazine (DTIC) 375 mg/m^2.
干预措施: dacarbazine (Drug)
ABVD
ABVD consists of doxorubicin 25 mg/m^2, bleomycin 10 units per square meter (units/m^2), vinblastine 6 mg/m^2, and dacarbazine (DTIC) 375 mg/m^2.
干预措施: doxorubicin (Drug)
ABVD
ABVD consists of doxorubicin 25 mg/m^2, bleomycin 10 units per square meter (units/m^2), vinblastine 6 mg/m^2, and dacarbazine (DTIC) 375 mg/m^2.
干预措施: bleomycin (Drug)
ABVD
ABVD consists of doxorubicin 25 mg/m^2, bleomycin 10 units per square meter (units/m^2), vinblastine 6 mg/m^2, and dacarbazine (DTIC) 375 mg/m^2.
干预措施: vinblastine (Drug)
ABVD
ABVD consists of doxorubicin 25 mg/m^2, bleomycin 10 units per square meter (units/m^2), vinblastine 6 mg/m^2, and dacarbazine (DTIC) 375 mg/m^2.
干预措施: dacarbazine (Drug)
结局指标
主要结局
Modified Progression-free Survival (mPFS) Per Independent Review Facility (IRF)
时间窗: 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.
次要结局
- Overall Survival (OS)(Baseline until death (approximately up to 4 years))
- Complete Remission (CR) Rate at the End of Randomized Regimen Per IRF(Baseline up to end of randomized regimen (approximately 1 year))
- 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))
- Disease-free Survival (DFS) Per IRF(From CR until PD or death (approximately up to 4 years))
- Overall Response Rate (ORR) Per IRF(Baseline up to end of randomized regimen (approximately 1 year))
- Duration of Response (DOR) Per IRF(From first documented response until PD (approximately 4 years))
- Duration of Complete Remission (DOCR) Per IRF(From first documentation of CR until PD (approximately 4 years))
- 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))
- Complete Remission (CR) Per IRF Rate at the End of Frontline Therapy(Baseline up to end of frontline therapy (approximately 4 years))
- Positron Emission Tomography (PET) Negativity Rate Per IRF at Cycle 2(Cycle 2 Day 25)
- 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))
- 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))