Lymphoma
Conditions
Keywords
Drug Therapy
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.
Interventions
DRUGBrentuximab Vedotin
Brentuximab vedotin IV infusion
DRUGCyclophosphamide
Cyclophosphamide IV infusion
DRUGDoxorubicin
Doxorubicin IV infusion
DRUGPrednisone
Prednisone tablets
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) by Independent Review Facility (IRF) Assessment Per Revised Response Criteria for Malignant Lymphoma | Up to approximately 7 months | 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. |
| Percentage of Participants Who Experienced at Least One Treatment Emergent Adverse Event (TEAE) | Up to approximately 7 months | 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. |
| Number of Participants With Abnormal Changes From Baseline in Laboratory Measurements | Up to approximately 7 months | 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. |
| Number of Participants With Abnormal Changes From Baseline in Vital Sign Measurements (Blood Pressure) | Up to approximately 7 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CR Rate by IRF Assessment Per Revised Response Criteria for Malignant Lymphoma | Up to approximately 7 months | 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. |
| 1-Year Progression Free Survival (PFS) Rate by IRF Assessment Per Revised Response Criteria for Malignant Lymphoma | Month 12 | 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. |
| 1-Year Overall Survival (OS) Rate | Month 12 | 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. |
| ORR by IRF Per 2014 Lugano Classification | Up to approximately 7 months | 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. |
| ORR by Investigator Assessment Per 2014 Lugano Classification | Up to approximately 7 months | 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. |
| CR Rate by IRF Per 2014 Lugano Classification | Up to approximately 7 months | 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. |
| CR Rate by Investigator Assessment Per 2014 Lugano Classification | Up to approximately 7 months | 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 to Response (TTR) by IRF Per 2014 Lugano Classification | Up to approximately 7 months | 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 to Response (TTR) by Investigator Assessment Per 2014 Lugano Classification | Up to approximately 7 months | 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. |
| 1-Year PFS Rate by IRF Per 2014 Lugano Classification | Month 12 | 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. |
| 1-Year PFS Rate by Investigator Assessment Per 2014 Lugano Classification | Month 12 | 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. |
| Duration of Response (DOR) by Investigator Assessment Per 2014 Lugano Classification | Up to approximately 36 months | 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. |
| Serum Antibody-Drug Conjugate (ADC) Concentration | 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 | 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. |
| Plasma Monomethyl Auristatin E (MMAE) Concentration | 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 | 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 | 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 | 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) | Preinfusion on Day 1 of each cycle up to Cycle 8, and anytime within 30 days after last dose; each cycle = 21 days | — |
Countries
China
Contacts
STUDY_DIRECTORMedical Director
Takeda
Participant flow
Recruitment details
Participants took part in the study at 14 investigative sites in China from 10 February 2023 to 27 April 2025. The study is ongoing.
Pre-assignment details
A total of 52 participants with newly diagnosed CD30-positive (CD30+) peripheral T-cell lymphomas (PTCL) were enrolled in the study and treated with brentuximab vedotin in combination with cyclophosphamide, doxorubicin (hydroxydaunorubicin) and prednisone (CHP). The results presented are until the primary completion date.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 48.9 years STANDARD_DEVIATION 15.49 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 52 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 52 |
| other Total, other adverse events | 52 / 52 |
| serious Total, serious adverse events | 18 / 52 |
Outcome results
None listed