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)

Takeda

Status and phase: Active, not recruiting; Phase 2

Conditions: Lymphoma

Treatments: Drug: Prednisone; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Brentuximab Vedotin

Study type: Interventional

Funder types: Industry

Identifiers

NCT05673785

C25024

Details and patient eligibility

About

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.

Full 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.

Enrollment: 52 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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52 participants in 1 patient group

Brentuximab Vedotin + CHP

Experimental group

Description:

Brentuximab vedotin 1.8 mg/kg, intravenous (IV) infusion, within 1 hour of completing treatment with other IV agents, i.e., cyclophosphamide 750 mg/m\^2 and doxorubicin 50 mg/m\^2 IV, on Day 1 of each 21-day cycle, and prednisone 100 mg tablets, orally, on Days 1 through Day 5, for up to 8 cycles (6 months) or until progressive disease (PD), unacceptable toxicity, whichever occurs first.

Treatment:

Drug: Brentuximab Vedotin

Drug: Cyclophosphamide

Drug: Doxorubicin

Drug: Prednisone