A Study of Brentuximab Vedotin in Combination With Cyclophosphamide, Doxorubicin (Hydroxydaunorubicin), Prednisone (CHP) in Chinese Participants With CD30-Positive (CD30+) Peripheral T-Cell Lymphomas (PTCL)

Phase 2Active Not RecruitingNCT05673785

Takeda52 enrolled

Overview

This study will use a combination of Brentuximab vedotin with CHP to treat adult Chinese participants with CD30+ PTCL. The main aims of the study are to evaluate: * Side effect from the A+CHP * Check how much A+CHP stays in their blood over time. This will help Takeda to work out the best dose to give people in the future. * If A+CHP improves outcome of newly diagnosed CD30+ PTCL Brentuximab vedotin will be given through vein on Day 1 of each 21-day cycle. Cyclophosphamide and doxorubicin will be given through vein. Prednisone will be given orally daily on Days 1 through 5.

The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat CD30+ PTCL in Chinese participants. This study will look at the efficacy, safety, and pharmacokinetics (PK) of A+CHP as frontline treatment for newly diagnosed CD30+ PTCL. The study will enroll approximately 52 participants. Participants will be enrolled in a single group to receive: • Brentuximab vedotin 1.8 milligrams per kilogram (mg/kg) + Cyclophosphamide 750 milligrams per square meter (mg/m\^2), Doxorubicin 50 mg/m\^2 and Prednisone 100 mg This multi-center trial will be conducted in China. The overall time to participate in this study is approximately 36 months.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Lymphoma

Brentuximab VedotinDRUG

Brentuximab vedotin IV infusion

CyclophosphamideDRUG

Cyclophosphamide IV infusion

DoxorubicinDRUG

Doxorubicin IV infusion

PrednisoneDRUG

Prednisone tablets

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Participants must have newly diagnosed CD30+ PTCL, per the Revised European American Lymphoma 2016 World Health Organization (WHO) classification, by local assessment. Tumor specimen must be submitted before enrollment for subsequent central pathology review to confirm histology (and anaplastic lymphoma kinase (ALK) status, if applicable), and CD30 expression. Eligible histologies include: 1. ALK-positive systemic anaplastic large cell lymphoma (sALCL) with an International Prognostic Index (IPI) score of ≥2. 2. ALK-negative sALCL. 3. PTCL- not otherwise specified (NOS). 4. Angioimmunoblastic T-cell lymphoma (AITL). 5. Enteropathy associated T-cell lymphoma (EATL). 6. Hepatosplenic T-cell lymphoma (HSTCL). 2. Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2. 3. Fluorodeoxyglucose (FDG)-avid disease by positron emission tomography (PET) imaging and measurable disease with at least 1 bidimensionally measurable lesion (\>1.5 cm in its largest dimension) by computed tomography (CT). 4. Suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) and immunogenicity sampling. 5. Clinical laboratory values as specified below at screening/baseline within 7 days before the first dose of study drug: 1. Total bilirubin must be ≤1.5 times the upper limit of normal (ULN) or ≤3 times the ULN for participants with Gilbert's disease or documented hepatic involvement with lymphoma. 2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be ≤3 times the ULN or ≤5 times the ULN for participants with an elevation that can be reasonably ascribed to the presence of metastatic disease in liver. 3. Serum creatinine must be \<2.0 milligram per deciliter (mg/dL) and/or creatinine clearance or calculated creatinine clearance \>40 milliliter (mL)/minute. 4. Hemoglobin must be ≥8 grams per deciliter (g/dL). (Red blood cell transfusion is allowed ≥14 days before assessment.) 5. Absolute neutrophil count \>1.5×10\^9/liter (L). 6. Platelet count ≥75×10\^9/L (unless documented bone marrow involvement with lymphoma). Exclusion Criteria: 1. Systemic anticancer therapy, including traditional Chinese medicine with antitumor indication for disease under study before the first dose of study drugs. 2. Major surgery within 28 days before the first dose of study drug. 3. Known human immunodeficiency virus (HIV)-positive status. 4. Known hepatitis B virus (HBV) surface antigen (HBsAg) seropositivity or active hepatitis C virus infection. Note: Participants who have positive HBV core antibody and are HBsAg negative can be enrolled, but must have an undetectable HBV viral load. 5. Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection. 6. Any of the following cardiovascular conditions or values within 6 months before the first dose of study drug: 1. Left-ventricular ejection fraction \<45%. 2. Myocardial infarction within 6 months of enrollment. 3. New York Heart Association Class III or IV heart failure. 7. Participants with current diagnosis of primary cutaneous CD30+ T-cell lymphoproliferative disorders and lymphomas. Participants with cutaneous anaplastic large cell lymphoma (ALCL) with extracutaneous tumor spread beyond locoregional lymph nodes are eligible (previous single-agent treatment to address cutaneous and locoregional disease is permissible). 8. Participants with mycosis fungoides (MF) \[including transformed MF\]. 9. Uncontrolled diabetes mellitus. 10. Baseline peripheral neuropathy ≥Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\], version 5.0). 11. History of progressive multifocal leukoencephalopathy (PML). 12. Previous treatment with brentuximab vedotin or CD30 monoclonal antibody.

Locations (16)

Beijing Cancer Hospital

Beijing, China

Peking University Third Hospital

Beijing, China

The First Hospital of Jilin University

Changchun, China

West China Hospital, Sichuan University

Chengdu, China

Chongqing University Cancer Hospital

Chongqing, China

Fujian Medical University Union Hospital

Fuzhou, China

Guangdong Provincial Peoples Hospital

Guangzhou, China

The First Affiliated Hospital of Zhejiang University school of medicine

Hangzhou, China

Anhui Provincial Cancer Hospital

Hefei, China

Shandong Cancer Hospital

Jinan, China

...and 6 more locations

Outcomes

Primary Outcomes

Overall Response Rate (ORR) by Independent Review Facility (IRF) Assessment Per Revised Response Criteria for Malignant Lymphoma

ORR by IRF assessment following the completion of study treatment was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) by IRF assessment using the International Working Group (IWG) Revised Response criteria following the completion of study treatment. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

Time frame: Up to approximately 7 months

Percentage of Participants Who Experienced at Least One Treatment Emergent Adverse Event (TEAE)

An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event that occurs after administration of the first dose of study treatment and up through 30 days after the last dose of study treatment.

Time frame: Up to approximately 7 months

Number of Participants With Abnormal Changes From Baseline in Laboratory Measurements

Laboratory parameters like Potassium, Aspartate Aminotransferase (AST), Bilirubin, Serum Gamma-glutamyl Transferase (GGT), High Glucose (Hyperglycemia), Neutrophils, Leukocytes, Platelets, and Hemoglobin were assessed. Intensity of changes in laboratory parameters were evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Time frame: Up to approximately 7 months

Number of Participants With Abnormal Changes From Baseline in Vital Sign Measurements (Blood Pressure)

Time frame: Up to approximately 7 months

Secondary Outcomes

CR Rate by IRF Assessment Per Revised Response Criteria for Malignant Lymphoma

CR rate by IRF assessment following the completion of study treatment was defined as the percentage of participants who achieved a CR by IRF assessment using the IWG Revised Response criteria following the completion of study treatment. CR was defined as disappearance of all evidence of disease.

Time frame: Up to approximately 7 months

1-Year Progression Free Survival (PFS) Rate by IRF Assessment Per Revised Response Criteria for Malignant Lymphoma

The 1-year PFS rate by IRF assessment using the IWG Revised Response criteria is defined as the percentage of participants alive and progression free at 1 year. PFS is defined as the time from the start of study treatment to the date of first documentation of PD, death due to any cause, or receipt of subsequent anticancer therapy to treat residual or PD, whichever occurs first.

Time frame: Month 12

1-Year Overall Survival (OS) Rate

The 1-year OS rate is defined as the percentage of participants alive at 1 year. OS is defined as the time from the start of study treatment to the date of death due to any cause.

Time frame: Month 12

ORR by IRF Per 2014 Lugano Classification

ORR by IRF per 2014 Lugano Classification, assessed by integrated computed tomography (CT) and positron emission tomography (PET)-based responses was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) by IRF following the completion of study treatment. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

Time frame: Up to approximately 7 months

ORR by Investigator Assessment Per 2014 Lugano Classification

ORR by investigator assessment per 2014 Lugano Classification, assessed by integrated computed tomography (CT) and positron emission tomography (PET)-based responses was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) by investigator assessment following the completion of study treatment. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

Data from ClinicalTrials.gov

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Time frame: Up to approximately 7 months

CR Rate by IRF Per 2014 Lugano Classification

CR rate by IRF per 2014 Lugano Classification, assessed by integrated CT and PET-based responses was defined as the percentage of participants who achieved a CR by IRF following the completion of study treatment. CR was defined as disappearance of all evidence of disease.

Time frame: Up to approximately 7 months

CR Rate by Investigator Assessment Per 2014 Lugano Classification

CR rate by investigator assessment per 2014 Lugano Classification, assessed by integrated CT and PET-based responses is defined as the percentage of participants who have achieved a CR by investigator assessment following the completion of study treatment. CR was defined as disappearance of all evidence of disease

Time frame: Up to approximately 7 months

Time to Response (TTR) by IRF Per 2014 Lugano Classification

TTR by IRF per 2014 Lugano Classification, assessed by integrated CT and PET-based responses was the time from date of first study drug administration to date of first documented objective response (CR or PR) by IRF following the completion of study treatment for responders. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

Time frame: Up to approximately 7 months

Time to Response (TTR) by Investigator Assessment Per 2014 Lugano Classification

TTR by investigator assessment per 2014 Lugano Classification, assessed by integrated CT and PET-based responses was the time from date of first study drug administration to date of first documented objective response (CR or PR) by investigator assessment following the completion of study treatment for responders. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.

Time frame: Up to approximately 7 months

1-Year PFS Rate by IRF Per 2014 Lugano Classification

The 1-year PFS rate by IRF per 2014 Lugano Classification is defined as the percentage of participants alive and progression free at 1 year. PFS is defined as the time from the start of study treatment to the date of first documentation of PD, death due to any cause, or receipt of subsequent anticancer therapy to treat residual or PD, whichever occurs first.

Time frame: Month 12

1-Year PFS Rate by Investigator Assessment Per 2014 Lugano Classification

The 1-year PFS rate by investigator assessment per 2014 Lugano Classification is defined as the percentage of participants alive and progression free at 1 year. PFS is defined as the time from the start of study treatment to the date of first documentation of PD, death due to any cause, or receipt of subsequent anticancer therapy to treat residual or PD, whichever occurs first.

Time frame: Month 12

Duration of Response (DOR) by Investigator Assessment Per 2014 Lugano Classification

DOR by investigator assessment using the 2014 Lugano Classification criteria is defined as the time between the first documentation of objective tumor response (CR or PR) by investigator assessment and the first subsequent documentation of objective tumor progression, death due to any cause, or receipt of subsequent anticancer therapy to treat residual or PD, whichever occurs first.

Time frame: Up to approximately 36 months

Serum Antibody-Drug Conjugate (ADC) Concentration

Antibody-Drug Conjugates (ADCs) are targeted cancer therapies that combine a monoclonal antibody with a cytotoxic drug to selectively deliver treatment to cancer cells while minimizing damage to healthy cells.

Time frame: Cycle 1:Predose on Day1 and at 30minutes (min),48and 96hours postdose;Cycle 2:Predose on Day1 and at 30min,48 and 168hours postdose;Predose on Day1 of Cycles3,5,6,7;Anytime once on Days15,21 of Cycles4,6,8;30 days post-last dose; each cycle=21days

Plasma Monomethyl Auristatin E (MMAE) Concentration

The plasma concentration of MMAE is a critical factor in determining the efficacy and safety of ADCs.

Number of Participants Who Are Antidrug Antibodies (ADA) Negative, ADA Transiently and Persistently Positive

Time frame: Pre-infusion on Day 1 of each cycle up to Cycle 8, and anytime within 30 days after last dose; each cycle = 21 days.

ADA Titer in Participants Positive for ADA Post Baseline

Time frame: Pre-infusion on Day 1 of each cycle up to Cycle 8, and anytime within 30 days after last dose; each cycle = 21 days.

Number of Participants With Negative and Positive Neutralizing Antibody Status (NAb)

Time frame: Preinfusion on Day 1 of each cycle up to Cycle 8, and anytime within 30 days after last dose; each cycle = 21 days

A Study of Brentuximab Vedotin in Combination With Cyclophosphamide, Doxorubicin (Hydroxydaunorubicin), Prednisone (CHP) in Chinese Participants With CD30-Positive (CD30+) Peripheral T-Cell Lymphomas (PTCL)

Overview

Conditions

Interventions

Eligibility

Locations (16)

Outcomes

Primary Outcomes

Secondary Outcomes