A Study of Brentuximab Vedotin and CHP in Frontline Treatment of PTCL With Less Than 10% CD30 Expression

Study Overview
=================
Brief Summary
-----------------
This clinical trial will study brentuximab vedotin with CHP to find out if the drugs work for people who have certain types of peripheral T-cell lymphoma (PTCL). It will also find out what side effects occur when brentuximab vedotin and CHP are used together. A side effect is anything the drugs do besides treating cancer. CHP is a type of chemotherapy that uses three drugs (cyclophosphamide, doxorubicin, and prednisone). CHP is approved by the FDA to treat certain types of PTCL.

Official Title
-----------------
A Dual-cohort, Open-label, Phase 2 Study of Brentuximab Vedotin and CHP (A+CHP) in the Frontline Treatment of Subjects With Peripheral T-cell Lymphoma (PTCL) With Less Than 10% CD30 Expression

Conditions
-----------------
Peripheral T-cell Lymphoma

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Newly diagnosed PTCL, excluding systemic anaplastic large cell lymphoma (sALCL), per the Revised European-American Lymphoma World Health Organization (WHO) 2016 classification The following non-sALCL PTCL subtypes are eligible: PTCL - not otherwise specified (PTCL-NOS) Angioimmunoblastic T-cell lymphoma (AITL) Adult T-cell leukemia/lymphoma (ATLL; acute and lymphoma types only, must be positive for human T cell leukemia virus 1) Enteropathy-associated T-cell lymphoma (EATL) Hepatosplenic T-cell lymphoma Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITCL) Indolent T-cell lymphoproliferative disorder (T-LPD) of the gastrointestinal (GI) tract Follicular T-cell lymphoma Nodal peripheral T-cell lymphoma with T-follicular helper (TFH) phenotype CD30 expression <10% by local assessment in tumor containing lymph node or other extranodal soft tissue biopsy Fluorodeoxyglucose (FDG)-avid disease by PET and measurable disease of at least 1.5 cm by CT, as assessed by the site radiologist An Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 Exclusion Criteria Current diagnosis of any of the following: sALCL Primary cutaneous T-cell lymphoproliferative disorders and lymphomas Mycosis fungoides (MF), including transformed MF History of another primary invasive cancer, hematologic malignancy, or myelodysplastic syndrome that has not been in remission for at least 3 years. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., 5-year OS ≥90%), such as carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer. History of progressive multifocal leukoencephalopathy (PML). Cerebral/meningeal disease related to the underlying malignancy. Prior treatment with brentuximab vedotin or doxorubicin. Baseline peripheral neuropathy Grade 2 or higher (per the NCI CTCAE, Version 4.03) or subjects with the demyelinating form of Charcot-Marie-Tooth syndrome. Left ventricular ejection fraction less than 45% or symptomatic cardiac disease (including symptomatic ventricular dysfunction, symptomatic coronary artery disease, and symptomatic arrhythmias), or myocardial infarction within the past 6 months, or previous treatment with complete cumulative dose of >300 mg/m2 of doxorubicin. Any uncontrolled Grade 3 or higher (per the National Cancer Institute's Common Terminology Criteria for Adverse Events, NCI CTCAE Version 4.03) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study drug. Routine antimicrobial prophylaxis is permitted.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CD30-negative Cohort<br>Participants with CD30 expression level < 1% | Drug: brentuximab vedotin<br>* 1.8 mg/kg administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle<br>* Other names: ADCETRIS;Drug: cyclophosphamide<br>* 750 mg/m^2 administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle<br>Drug: doxorubicin<br>* 50 mg/m^2 administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle<br>Drug: prednisone<br>* 100 mg daily administered orally on Days 1-5 of each cycle<br>|
| Experimental: CD30-positive Cohort<br>Participants with CD30 expression level ≥1% to < 10% | Drug: brentuximab vedotin<br>* 1.8 mg/kg administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle<br>* Other names: ADCETRIS;Drug: cyclophosphamide<br>* 750 mg/m^2 administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle<br>Drug: doxorubicin<br>* 50 mg/m^2 administered intravenously (IV; into the vein) on Day 1 of each 21 -day cycle<br>Drug: prednisone<br>* 100 mg daily administered orally on Days 1-5 of each cycle<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) per blinded independent central review (BICR) using Revised Response Criteria for Malignant Lymphoma criteria (Cheson 2007) | ORR is defined as the proportion of participants with complete response (CR) or partial response (PR) at the completion of study treatment | From start of study treatment up to approximately 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response (CR) rate per BICR | CR rate is defined as the proportion of participants with CR following the completion of study treatment using Revised Response Criteria of Malignant Lymphoma (Cheson 2007). | From start of study treatment up to approximately 7 months | 
| Progression-free survival (PFS) per BICR | Time from start of treatment to the first documented disease progression or death from any cause, whichever comes first | Up to approximately 3 years | 
| Overall survival | Time from first dose to death due to any cause | Up to approximately 3 years | 
| Duration of response (DOR) per BICR | Time from first occurrence of an objective response to the date of disease progression or death from any cause, whichever comes first | Approximately 3 years | 
| ORR per BICR per modified Lugano criteria (Cheson 2014) | ORR is defined as the proportion of participants with CR or PR at the completion of study treatment | From start of study treatment up to approximately 7 months | 
| Incidence of adverse events | An adverse event is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment | From start of study treatment up to approximately 7 months | 
| Incidence of laboratory abnormalities | To be summarized using descriptive statistics. | From start of study treatment up to approximately 7 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CD30-positive, CD30-negative, Seattle Genetics