ECHELON-2: A Comparison of Brentuximab Vedotin and CHP With Standard-of-care CHOP in the Treatment of Patients With CD30-positive Mature T-cell Lymphomas

Study Overview
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Brief Summary
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This is a double-blind, randomized, multicenter, phase 3 clinical trial to compare the efficacy and safety of brentuximab vedotin in combination with CHP with the standard-of-care CHOP in patients with CD30-positive mature T-cell lymphomas.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of Brentuximab Vedotin and CHP (A+CHP) Versus CHOP in the Frontline Treatment of Patients With CD30-positive Mature T-cell Lymphomas

Conditions
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Anaplastic Large-Cell Lymphoma, Non-Hodgkin Lymphoma, T-Cell Lymphoma

Intervention / Treatment
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* Drug: brentuximab vedotin
* Drug: doxorubicin
* Drug: prednisone
* Drug: vincristine
* Drug: cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly diagnosed, CD30-positive mature T-cell lymphomas Fluorodeoxyglucose (FDG)-avid disease by PET and measurable disease of at least 1.5 cm by CT Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 Exclusion Criteria: History of another primary invasive malignancy that has not been in remission for at least 3 years Current diagnosis of primary cutaneous CD30-positive T-cell lymphoproliferative disorders and lymphomas or mycosis fungoides History of progressive multifocal leukoencephalopathy (PML) Cerebral/meningeal disease related to the underlying malignancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CHOP<br>cyclophosphamide, doxorubicin, vincristine, and prednisone | Drug: doxorubicin<br>* 50 mg/m2 every 3 weeks by IV infusion for 6-8 cycles<br>Drug: prednisone<br>* 100 mg on Days 1 to 5 of each 3-week cycle, orally for 6-8 cycles<br>Drug: vincristine<br>* 1.4 mg/m2 (maximum 2 mg) every 3 weeks by IV infusion for 6-8 cycles<br>Drug: cyclophosphamide<br>* 750 mg/m2 every 3 weeks by IV infusion for 6-8 cycles<br>|
| Experimental: A+CHP<br>brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone | Drug: brentuximab vedotin<br>* 1.8 mg/kg every 3 weeks by IV infusion for 6-8 cycles<br>* Other names: Adcetris; SGN-35;Drug: doxorubicin<br>* 50 mg/m2 every 3 weeks by IV infusion for 6-8 cycles<br>Drug: prednisone<br>* 100 mg on Days 1 to 5 of each 3-week cycle, orally for 6-8 cycles<br>Drug: cyclophosphamide<br>* 750 mg/m2 every 3 weeks by IV infusion for 6-8 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Per Independent Review Facility (IRF) | The time from the date of randomization to the date of first documentation of progressive disease (PD), death due to any cause, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease whichever occurred first. | Up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Per IRF in Patients With Systemic Anaplastic Large Cell Lymphoma (sALCL) | The time from the date of randomization to the date of first documentation of progressive disease (PD), death due to any cause, or receipt of subsequent anticancer chemotherapy to treat residual or progressive disease whichever occurred first. | Up to 60 months | 
| Complete Remission (CR) Rate Per IRF at End of Treatment (EOT) | The count of participants with CR per IRF following the completion of study treatment (at end of treatment or at the first assessment after the last dose of study treatment and prior to long-term follow-up) according to the Revised Response Criteria for Malignant Lymphoma. | Up to 8.34 months | 
| Overall Survival (OS) | The time from randomization to death due to any cause. | Up to 90 months | 
| Objective Response Rate (ORR) Per IRF at End of Treatment | The count of participants with CR or partial response (PR) per IRF following the completion of study treatment (at end of treatment or the first assessment after the last dose of study treatment and prior to long-term follow-up) according to the Revised Response Criteria for Malignant Lymphoma. | Up to 8.34 months | 
| Incidence of Adverse Events (AEs) | Any untoward medical occurrence in a clinical investigational participant administered a medicinal product which does not necessarily have a causal relationship with this treatment. | Up to 8.28 months | 
| Incidence of Laboratory Abnormalities | Number of participants who experienced a Grade 3 or higher laboratory toxicity. | Up to 8.28 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibodies, Monoclonal, Antibody-Drug Conjugate, Antigens, CD30, Drug Therapy, Hematologic Diseases, Lymphoma, Monomethyl auristatin E, Lymphoma, T-Cell, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Anaplastic