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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 82
- Locations
- 80
- Primary Endpoint
- Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by Revised Response Criteria for Malignant Lymphoma Criteria (Cheson 2007) by Central CD30 Assessment
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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:
- •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.
Arms & Interventions
CD30-negative Cohort
Participants with CD30 expression level < 1%
Intervention: cyclophosphamide (Drug)
CD30-negative Cohort
Participants with CD30 expression level < 1%
Intervention: brentuximab vedotin (Drug)
CD30-positive Cohort
Participants with CD30 expression level ≥1% to < 10%
Intervention: brentuximab vedotin (Drug)
CD30-negative Cohort
Participants with CD30 expression level < 1%
Intervention: doxorubicin (Drug)
CD30-negative Cohort
Participants with CD30 expression level < 1%
Intervention: prednisone (Drug)
CD30-positive Cohort
Participants with CD30 expression level ≥1% to < 10%
Intervention: doxorubicin (Drug)
CD30-positive Cohort
Participants with CD30 expression level ≥1% to < 10%
Intervention: cyclophosphamide (Drug)
CD30-positive Cohort
Participants with CD30 expression level ≥1% to < 10%
Intervention: prednisone (Drug)
Outcomes
Primary Outcomes
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by Revised Response Criteria for Malignant Lymphoma Criteria (Cheson 2007) by Central CD30 Assessment
Time Frame: At EOT or the first assessment after the last dose of study treatment (prior to long term follow-up or initiation of subsequent anti-cancer therapies); up to 41.91 months
ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) following the completion of study treatment (at end of treatment \[EOT\]). CR and PR per Cheson 2007: CR was defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy and PR was defined as at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses.
Secondary Outcomes
- Complete Response (CR) Rate Per BICR (Cheson 2007) by Central CD30 Assessment(At EOT or the first assessment after the last dose of study treatment (prior to long term follow-up or initiation of subsequent anti-cancer therapies); up to 41.91 months)
- Progression Free Survival (PFS) Per BICR (Cheson 2007) by Central CD30 Assessment(From the first dose of study treatment to first documentation of objective tumor progression or death due to any cause or censoring, whichever came first (approximately 61.7 months))
- Overall Survival (OS) by Central CD30 Assessment(From the first dose of study treatment until death or censoring date, whichever came first (approximately 61.7 months))
- Duration of Response (DOR) Per BICR (Cheson 2007) by Central CD30 Assessment(From the first documented CR or PR until the first documentation of tumor progression, death or censoring date, whichever came first (up to 61.7 months))
- ORR Per BICR by Modified Lugano Criteria (Cheson 2014) by Central CD30 Assessment(At EOT or the first assessment after the last dose of study treatment (prior to long term follow-up or initiation of subsequent anti-cancer therapies); up to 41.91 months)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Related Adverse Events by Local CD30 Assessment(From first dose of the study treatment (Day 1) up to 30-37 days after the last dose of study treatment (approximately up to 6.6 months))
- Number of Participants With Treatment Emergent Laboratory Abnormalities as Per Worst Post Baseline Grading, by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 by Local CD30 Assessment(From first dose of the study treatment (Day 1) up to 30-37 days after the last dose of study treatment (approximately up to 6.6 months))