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 expressio
- Conditions
- Peripheral T-cell LymphomaMedDRA version: 21.1Level: LLTClassification code: 10034624Term: Peripheral T-cell lymphoma unspecified NOS Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-509155-14-00
- Lead Sponsor
- Seagen Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 113
Age 18 years or older, Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 12 months after the last dose of cyclophosphamide or 6 months after the last dose of other study treatment, whichever is later., Subjects or their legally authorized representative must provide written informed consent. If informed consent is obtained from a legally authorized representative for a subject who is unable to provide informed consent at study entry, but the subject is later able to provide informed consent, the investigator must obtain written informed consent from the subject., Newly diagnosed PTCL, excluding sALCL, per the Revised European-American Lymphoma World Health Organization (WHO) 2016 classification, The following non-sALCL PTCL subtypes are eligible: a. PTCL – not otherwise specified (PTCL-NOS) b. Angioimmunoblastic T-cell lymphoma (AITL) c. Adult T-cell leukemia/lymphoma (ATLL; acute and lymphoma types only, must be positive for human T cell leukemia virus 1) d. Enteropathy-associated T-cell lymphoma (EATL) e. Hepatosplenic T-cell lymphoma f. Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITCL) g. Indolent T-cell lymphoproliferative disorder (T-LPD) of the gastrointestinal (GI) tract h. Follicular T-cell lymphoma i. Nodal PTCL with T-follicular helper (TFH) phenotype 4. CD30 expression, 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, The following required baseline laboratory data: ? bilirubin =1.5X upper limit of normal (ULN) or =3X ULN for subjects with Gilbert’s disease or documented hepatic involvement with lymphoma ? alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =3X ULN or =5X ULN for subjects with document hepatic involvement with lymphoma ? serum creatinine =2X ULN ? estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) study equation provided below. eGFR (mL/min/1.73 m2 ) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African American) Conversion to creatinine clearance (CrCl) (mL/min) from eGFR using the Mosteller body surface area (BSA) equation and dividing by 1.73 to determine dosing holds. BSA (m2 ) = (Height [cm] x Weight [kg] / 3600)1/2 CrCl (mL/min) = (eGFR [mL/min/1.73 m2 ] x BSA [m2 ])/1.73 ? 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), The following requirements for subjects who are human immunodeficiency virus (HIV)-positive: ? CD4+ T-cell counts =350 cell/µL within 28 days of Day 1 ? No acquired immune deficiency syndrome-defining opportunistic infection within the past 12 months ? On established highly active antiretroviral therapy for at least 4 weeks with an HIV viral load less than 400 copies/mL within 28 days of Day 1, Females of childbearing potential must have a negative serum beta human chorionic gonadotrophin (ß-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 12 m
Current diagnosis of any of the following: a. sALCL b. Primary cutaneous T-cell lymphoproliferative disorders and lymphomas c. Mycosis fungoides (MF), including transformed MF, Females who are pregnant or breastfeeding, Subjects with a known hypersensitivity to any excipient contained in any of the drug formulations of study treatments, Subjects with known urinary outflow obstruction, Any other condition that in the opinion of the investigator would impact patient safety or ability to participate in the trial, Contraindications to any of the study drugs, Has received a live vaccine within 30 days prior to the first dose of study drug and must not receive a live vaccine within 90 days after the last dose of study drug. Vaccines other than live vaccines are permitted, 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 (eg, 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 (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., Current therapy with other systemic anti-neoplastic or investigational agents. Participation in other clinical trials for any condition is not allowed. Participation in observational studies is permitted.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the ORR per blinded independent central review (BICR) using Revised Response Criteria for Malignant Lymphoma criteria;Secondary Objective: To evaluate the complete response (CR) rate following completion of study treatment, To evaluate the progression-free survival PFS, To evaluate overall survival (OS), To evaluate DOR, To evaluate ORR per BICR, using modified Lugano criteria, To evaluate the safety and tolerability;Primary end point(s): ORR per BICR following the completion of study treatment using Revised Response Criteria for Malignant Lymphoma criteria
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Complete response rate per BICR;Secondary end point(s):PFS per BICR;Secondary end point(s):OS;Secondary end point(s):DOR per BICR;Secondary end point(s):ORR per BICR, using modified Lugano criteria;Secondary end point(s):Type, incidence, severity, seriousness, and relatedness of adverse events;Secondary end point(s):Laboratory abnormalities