Study of Brentuximab Vedotin in Participants With Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to assess the antitumor efficacy of single-agent brentuximab vedotin 1.8 mg/kg administered intravenously (IV) every 3 weeks, as measured by the overall objective response rate (ORR) in patients with r/r sALCL following at least 1 multiagent chemotherapy regimen (cyclophosphamide, doxorubicin hydrochloride [hydroxydaunorubicin], vincristine sulfate [Oncovin], and prednisone [CHOP] or equivalent multiagent chemotherapy regimens with curative intent).

Official Title
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A Phase 4, Open-label, Single-Arm Study of Brentuximab Vedotin in Patients With Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: Brentuximab vedotin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants age 18 years or older, with relapsed or refractory sALCL who have previously received at least 1 multiagent chemotherapy Bidimensional measurable disease An Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Female participants who are postmenopausal for at least 1 year before the screening visit, surgically sterile, or agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 30 days after the last dose of study drug, or agree to practice true abstinence Male participants who agree to practice effective barrier contraception during the entire study treatment period through 6 months after the last dose of study drug or agree to practice true abstinence Clinical laboratory values as specified in the study protocol Exclusion Criteria: Previous treatment with brentuximab vedotin. Previously received an allogeneic transplant. Participants with current diagnosis of primary cutaneous anaplastic large cell lymphoma [ALCL] (participants whose ALCL has transformed to sALCL are eligible). Known cerebral/meningeal disease including signs or symptoms of progressive multifocal leukoencephalopathy (PML) Female participants who are lactating and breastfeeding or pregnant Known human immunodeficiency virus (HIV) positive Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brentuximab Vedotin 1.8 mg/kg<br>Participants received brentuximab vedotin 1.8 mg/kg as a 30 minute intravenous (IV) infusion on Day 1 of each 3 week cycle. Participants with stable disease or better and without unacceptable toxicity were to receive a minimum of 8 cycles with the opportunity to receive a maximum of 16 cycles. | Drug: Brentuximab vedotin<br>* Brentuximab vedotin IV infusion<br>* Other names: ADCETRIS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR was defined as the percentage of participants with a complete remission (CR) or partial remission (PR) by Independent Review Facility (IRF) response assessment according to the International Working Group (IWG) Revised Response Criteria for Malignant Lymphoma. CR is defined as the disappearance of all evidence of disease and PR is defined as regression of measurable disease and no new sites. | Up to data cut-off date: 04 May 2021 (Up to approximately 7 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) as Per IRF | DOR was defined as the time between initial response and documented tumor progression in the subset of participants who achieved an objective response, either CR or PR. DOR per IRF was based upon the radiological assessment of measured lesions from an independent review facility. DOR was censored on the date of the last disease assessment documenting absence of progressive disease (PD) for participants who were lost to follow-up, withdrew consent, started a new anticancer therapy other than SCT, or discontinued treatment due to undocumented PD after the last adequate disease assessment. | Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years) | 
| Progression-free Survival (PFS) as Per IRF | PFS is defined as the time from start of study treatment to first documentation of objective tumor progression or to death due to any cause, whichever comes first. PFS per IRF is based upon the radiological assessment from an independent review facility. | Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years) | 
| Complete Remission Rate (CRR) | CRR is defined as percentage of participants with CR. CR is defined as the disappearance of all evidence of disease. | Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years) | 
| Overall Survival (OS) | OS is defined as the time from start of study treatment to date of death due to any cause. | Until death or the data cut-off date: 4 May 2021 (Up to approximately 7 years) | 
| Percentage of Participants Receiving Hematopoietic Stem Cell Transplant (SCT) Following Treatment With Brentuximab Vedotin |  | Until disease progression, death, or the data cut-off date: 4 May 2021 (Up to approximately 7 years) | 
| Percentage of Participants With Adverse Events (AEs), Serious Adverse Events, Related Adverse Events and Adverse Events by Severity (Grade 3 or Higher) | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; the untoward medical occurrence does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. This includes any newly occurring event, or a previous condition that has increased in severity or frequency since the administration of study drug. Serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly/birth defect, or is a medically important event. | From first dose up to 30 days post last dose of study drug (Up to approximately 17 months) | 
| Concentration of Serum Antibody-drug Conjugate (ADC) at the End of Infusion |  | Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion | 
| Concentration of Serum Total Antibody (TAb) Conjugate Plus Free Total Antibody |  | Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion | 
| Maximum Concentration for Unconjugated Drug- Monomethyl Auristatin E (MMAE) |  | Cycle 1, Day 1 and Cycle 3, Day 1 at the end of infusion | 
| Percentage of Participants With Presence of Anti-Therapeutic Antibodies (ATA) and Neutralizing Antidrug Antibody (Nab) to Brentuximab Vedotin |  | Up to 16 cycles (each cycle = 21 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Anaplastic Large-cell, Relapsed, Refractory, Antigens, CD30, Antibody-Drug Conjugate, Antibodies, Monoclonal, Lymphoma, Non-Hodgkin, Lymphoma, Large-Cell, Anaplastic, monomethyl auristatin E, Drug Therapy, Immunotherapy, Hematologic Diseases