Title 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
IRB SEGE 2412
Hospital Main Campus
Phase Phase 3
Disease Lymphoma, Lymphoma, Anaplastic Large Cell , Lymphoma, Non - Hodgkin
Drug Brentuximab Vedotin, CHOP
- To compare the progression-free survival (PFS) as determined by an independent review facility (IRF) between the 2 treatment arms
- To compare the PFS per IRF between the 2 treatment arms for patients with systemic anaplastic large cell lymphoma (sALCL)
- To compare the complete remission (CR) rate per IRF following the completion of study treatment between the 2 treatment arms
- To compare overall survival (OS) between the 2 treatment arms
- To evaluate the safety and tolerability of the 2 treatment arms
- To evaluate medical resource utilization (MRU) and calculate utility values
- To characterize the incidence of antitherapeutic antibodies (ATA) to brentuximab vedotin
- Patients with newly diagnosed, CD30-positive mature T-cell lymphomas per the Revised European- American Lymphoma WHO 2008 classification by local assessment. See Section 7.1.1 for details on definition of CD30 positivity. Eligible histologies are limited to the following:
- ALK-positive sALCL with an IPI score greater than or equal to 2
- ALK-negative sALCL
- Adult T-cell leukemia/lymphoma (ATLL; acute and lymphoma types only, must be positive for human Tcell leukemia virus 1)
- Enteropathy-associated T-cell lymphoma (EATL)
- Hepatosplenic T-cell lymphoma
- Fluorodeoxyglucose (FDG)-avid disease by PET and measurable disease of at least 1.5 cm by CT, as assessed by the site radiologist.
- Age greater than or equal to 18 years.
- An Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
- The following required baseline laboratory data:
- bilirubin ≤ 1.5X upper limit of normal (ULN) or ≤ 3X ULN for patients with Gilberts disease or documented hepatic involvement with lymphoma
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3X ULN or ≤ 5X ULN for patients with document hepatic involvement with lymphoma
- serum creatinine ≤ 2X ULN
- absolute neutrophil count (ANC) ≥ 1000 μL (unless documented bone marrow involvement with lymphoma)
- platelet count ≥ 50,000/μL (unless documented bone marrow involvement with lymphoma).
- Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotrophin (B-hCG) pregnancy test result within 7 days prior to the first dose of study treatment and must agree to use an effective contraception method during the study and for at least 6 months following the last dose of study drug. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.
- Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 6 months following the last dose of study drug.
- Patients or their legally authorized representative must provide written informed consent.
- History of another primary invasive cancer, hematologic malignancy, or myelodysplastic syndrome that has not been in remission for at least 3 years.
- Current diagnosis of any of the following:
- Primary cutaneous CD30-positive T-cell lymphoproliferative disorders and lymphomas. Cutaneous ALCL with extracutaneous tumor spread beyond locoregional lymph nodes is eligible (previous single agent treatment to address cutaneous and locoregional disease is permissible).
- Mycosis fungoides (MF), including transformed MF
- History of progressive multifocal leukoencephalopathy (PML).
- Cerebral/meningeal disease related to the underlying malignancy.
- Prior treatment with brentuximab vedotin.
- Baseline peripheral neuropathy ≥ Grade 2 (per the NCI CTCAE, Version 4.03) or patients 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 doses of doxorubicin or other anthracyclines.
- Any active Grade 3 (per the NCI CTCAE, Version 4.03) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment; any known human immunodeficiency virus (HIV) infection, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.
- Current therapy with other systemic anti-neoplastic or investigational agents.
- Females who are pregnant or breastfeeding.
- Patients with a known hypersensitivity to any excipient contained in any of the drug formulations of study treatments.
- Patients with known urinary outflow obstruction.