Clinical trial NCT02939014: Brentuximab Vedotin in Chinese Participants With Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL)
Official title: A Phase 2, Single-Arm, Open-label Study of Brentuximab Vedotin in Chinese Patients With Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hodgkin Disease
Lymphoma, Large-Cell, Anaplastic
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2016-10-19
Enrollment: 39
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: The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics (PK) of brentuximab vedotin as a single agent in Chinese participants with relapsed/refractory CD30+ Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL).

Detailed description: The drug being tested in this study is called brentuximab vedotin. This study will look at efficacy, safety and PK of brentuximab vedotin in Chinese participants with relapsed/refractory CD30+ HL or sALCL.

The study will enroll approximately 30 patients. Participants will receive:

• Brentuximab vedotin 1.8 mg/kg

All participants will be administered IV infusion on Day 1 each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles.

This multi-center trial will be conducted in China only. The overall time to participate in this study is 3.5 years. Participants will make multiple visits to the clinic, and will be followed for overall survival (OS) every 12 weeks until death, withdrawal of consent, 18 months after end of treatment (EOT) or study closure, whichever occurs first.

Eligibility criteria: Inclusion Criteria:

1. Have histologically confirmed CD30+ hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (sALCL). Immunohistochemistry or flow cytometry may be performed on either original diagnostic biopsy material or biopsy of relapsed disease, and pathology reports of CD30+ or their copies should be retained at the site.
2. With CD30+ HL or sALCL who have relapsed from or are refractory to previous treatments.
3. Fluorodeoxyglucose (FDG)- positron emission tomography (PET) positive and measurable disease of at least 1.5 cm in the longest diameter by computed tomography (CT), as assessed by the site.
4. Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
5. Suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) sampling.
6. Must have the following required screening laboratory data. Participants must not have received recombinant granulocyte-colony stimulating factor (G-CSF) or platelet transfusion within 1 week before the screening hematology assessment.

   1. Absolute neutrophil count ≥1500/μL.
   2. Platelet count ≥75,000/μL.
   3. Serum bilirubin level ≤1.5 times the upper limit of the normal range (ULN).
   4. Serum creatinine level ≤1.5 times the ULN.
   5. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the ULN.
7. Survival for 3 or more months must be expected.

Exclusion Criteria:

1. With current diagnosis of primary cutaneous anaplastic large cell lymphoma (ALCL) (participants with other organ involvement who have transformed to sALCL are eligible).
2. With any active viral, bacterial, or fungal infection within 2 weeks before the first dose of brentuximab vedotin.
3. With cardiac failure categorized as Class III or IV according to the New York Heart Association criteria, uncontrolled coronary artery disease or uncontrolled arrhythmia despite of appropriate medical therapy, or a history of myocardial infarction within 6 months before the first dose of brentuximab vedotin.
4. With uncontrolled diabetes mellitus.
5. Peripheral neuropathy ≥Grade 2.
6. With a history of another malignancy that has not been in remission for at least 3 years. The following are exempt from the 3-year limit:

   1. Nonmelanoma skin cancer.
   2. Curatively treated localized prostate cancer.
   3. Cervical carcinoma in situ.
7. With known cerebral/meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML).
8. With a positive result in the screening test for human immunodeficiency virus (HIV) antibody.
9. Known hepatitis B virus (HBV) surface antigen seropositive or positive hepatitis C virus (HCV) antibody. Note: participants who have positive HBV core antibody can be enrolled but must have an undetectable HBV viral load.
10. With a history of liver fibrosis or cirrhosis and clinical signs and symptoms indicating liver fibrosis or cirrhosis.
11. Have received autologous stem cell transplantation (auto-SCT) within 12 weeks before the first dose of brentuximab vedotin.
12. With history of allogeneic stem cell transplantation (allo-SCT).
13. Have received treatment for malignancies (including radiation, chemotherapy, and hormone therapy) within 4 weeks before the first dose of brentuximab vedotin and participants who have received treatment for malignancies with biologics (including molecular target drug) or radioisotopic therapy within 12 weeks before the first dose of brentuximab vedotin.
14. Have unresolved toxicity higher than Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] version 4.03) attributed to any prior therapy/procedure (excluding alopecia or non-clinically significant and asymptomatic laboratory abnormalities).
15. Have received systemic corticosteroids at doses greater than the equivalent of 20 mg/day of prednisone within 1 week before the first dose of brentuximab vedotin.
16. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of the safety and toxicity of the prescribed regimens.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment until disease progression death or end of treatment (approximately 12 months)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)
measure: Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events
timeFrame: First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)
measure: Number of Participants With Abnormal Vital Signs Reported as Adverse Events
timeFrame: First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)
Secondary outcomes:
measure: Complete Remission (CR) Rate
timeFrame: Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment, and every 12 weeks during PFS follow-up period, until disease progression death or end of treatment (approximately 12 months)
measure: Duration of Response (DOR)
timeFrame: Up to 3.2 years
measure: Progression Free Survival (PFS)
timeFrame: Up to 3.2 years
measure: Overall Survival (OS)
timeFrame: Up to 3.2 years
measure: B Symptom Resolution Rate
timeFrame: Day 1 of each cycle (each cycle was of 3 weeks) up to 30 days after last dose of study drug (approximately 12 months)
measure: Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC)
timeFrame: Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
measure: Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb)
timeFrame: Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
measure: Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE)
timeFrame: Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Brentuximab Vedotin ADC
timeFrame: Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
measure: Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb
timeFrame: Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE
timeFrame: Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
measure: AUC(0-∞): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC
timeFrame: Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
measure: AUC(0-∞): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for TAb
timeFrame: Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
measure: AUC(0-∞): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MMAE
timeFrame: Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose
measure: Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin
timeFrame: Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment until disease progression, death or end of treatment (approximately 12 months)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-san University Cancer Center
state: Guangdong
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province People's Hospital
state: Jiangsu
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References:
citation: Song Y, Guo Y, Huang H, Li W, Ke X, Feng J, Xu W, Miao H, Kinley J, Song G, Dai Y, Wang H, Zhu J. Phase II single-arm study of brentuximab vedotin in Chinese patients with relapsed/refractory classical Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Expert Rev Hematol. 2021 Sep;14(9):867-875. doi: 10.1080/17474086.2021.1942831. Epub 2021 Aug 24.