Clinical trial NCT05673785: 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)
Official title: A Phase 2, Single-Arm, Open-Label, Multicenter Study of Brentuximab Vedotin in Combination With Cyclophosphamide, Doxorubicin (Hydroxydaunorubicin), Prednisone (CHP) in the Frontline Treatment of Chinese Patients With CD30-Positive (CD30+) Peripheral T-Cell Lymphomas (PTCL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Lymphoma
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2023-01-06
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate (ORR) by Independent Review Facility (IRF) Assessment per Revised Response Criteria for Malignant Lymphoma
timeFrame: Up to approximately 7 months
measure: Percentage of Participants who Experience at Least One Treatment Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 7 months
measure: Percentage of Participants With Clinically Significant Laboratory Test Values
timeFrame: Up to approximately 7 months
measure: Percentage of Participants With Clinically Significant Vital Signs
timeFrame: Up to approximately 7 months
Secondary outcomes:
measure: CR Rate by IRF Assessment per Revised Response Criteria for Malignant Lymphoma
timeFrame: Up to approximately 7 months
measure: 1-Year Progression Free Survival (PFS) Rate by IRF Assessment per Revised Response Criteria for Malignant Lymphoma
timeFrame: Up to approximately 12 months
measure: 1-Year Overall Survival (OS) Rate
timeFrame: Up to approximately 12 months
measure: ORR by IRF and Investigator Assessment per 2014 Lugano Classification
timeFrame: Up to approximately 7 months
measure: CR Rate by IRF and Investigator Assessment per 2014 Lugano Classification
timeFrame: Up to approximately 7 months
measure: Time to Response (TTR) by IRF and Investigator Assessment per 2014 Lugano Classification
timeFrame: Up to approximately 7 months
measure: 1-Year PFS Rate by IRF and Investigator Assessment per 2014 Lugano Classification
timeFrame: Up to approximately 12 months
measure: Duration of Response (DOR) by Investigator Assessment per 2014 Lugano Classification
timeFrame: Up to approximately 36 months
measure: Serum Antibody-drug Conjugate (ADC) Concentration
timeFrame: Preinfusion and at multiple time points (Up to 96 hours [Cycle 1]/168 hours [Cycle 2]) postinfusion; Preinfusion up to Cycle 8, each cycle = 21 days
measure: Plasma Monomethyl Auristatin E (MMAE) Concentration
timeFrame: Preinfusion and at multiple time points (Up to 96 hours [Cycle 1]/168 hours [Cycle 2]) postinfusion; Preinfusion up to Cycle 8, each cycle = 21 days
measure: Percentage of Participants who are Antidrug Antibodies (ADA) Negative, ADA Transiently and Persistently Positive, ADA Titer, and Neutralizing Antidrug Antibody (Nab) Negative and Positive
timeFrame: Preinfusion on Day 1 of each cycle up to Cycle 8, each cycle = 21 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University school of medicine
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute & Hospital
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: