A Phase II Study of Single Agent Brentuximab Vedotin in Relapsed/Refractory CD30 Low (<10%) Mature T Cell Lymphoma (TCL)

Study Overview
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Brief Summary
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This study will include patients with mature T-cell lymphoma (MTCL) that has been treated with at least one type of chemotherapy, but is not responding or coming back after the previous treatment. This clinical trial uses a drug called Brentuximab Vedotin. The Food and Drug Administration (FDA) has approved Brentuximab Vedotin for sale in the United States for certain diseases. Brentuximab is still being studied in clinical trials like this one to learn more about what its side effects are and whether or not it is effective in the disease or condition being studied. Brentuximab Vedotin is a type of drug called an antibody drug conjugate (ADC). ADCs usually have 2 parts; a part that targets cancer cells (the antibody) and a cell killing part (the chemotherapy). Antibodies are proteins that are part of your immune system. They can stick to and attack specific targets on cells. The antibody part of Brentuximab Vedotin sticks to a target called CD30. CD30 is an important molecule on some cancer cells (including non Hodgkin lymphoma) and some normal cells of the immune system. The cell killing part of Brentuximab Vedotin is a chemotherapy called monomethyl auristatin E (MMAE). It can kill cells that the antibody part of Brentuximab Vedotin sticks to. Brentuximab Vedotin has also been shown to kill cancer cells with levels of CD30 that cannot be seen by traditional methods. This study is being done to test if the study drug has an effect on Mature T cell Lymphoma with such low levels of a target called CD30 and how your disease respond to the study drug.

Detailed Description
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Primary Objective • To determine overall response rate (CR+PR) of brentuximab vedotin in CD30 low (<10%) relapsed or refractory T cell lymphoma (TCL) Secondary Objective(s) Complete remission (CR) rate Duration of response (DOR) Progression free survival (PFS) Overall survival (OS) Time to treatment failure (TTF)

Official Title
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A Phase II Study of Single Agent Brentuximab Vedotin in Relapsed/Refractory CD30 Low (<10%) Mature T Cell Lymphoma (TCL)

Conditions
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T-cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Hepato-splenic T-cell Lymphoma, Adult T-cell Leukemia/Lymphoma, Enteropathy Associated T-cell Lymphoma, NK T-cell Lymphoma

Intervention / Treatment
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* Drug: Brentuximab vedotin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed relapsed/refractory CD30 low (<10%) TCL: including peripheral TCL not otherwise specified (PTCL NOS), angioimmunoblastic T cell lymphoma (AITL), hepato-splenic T cell lymphoma (HTCL), adult T cell leukemia/lymphoma (ATLL), enteropathy associated T cell lymphoma (EATL), adult T cell leukemia/lymphoma (ATLL), enteropathy associated T cell lymphoma (EATL), NK T cell lymphoma (NK/TCL) At least 1 prior chemotherapy regimen Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. ECOG Performance Status (PS) 3 will be permitted if the decreased PS is attributed to the lymphoma Adequate organ function Bilirubin ≤1.5X upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3X ULN even in patients with documented hepatic involvement with lymphoma Serum creatinine clearance ≥30 ml/min Absolute neutrophil count (ANC) ≥1000/μL (unless documented bone marrow involvement with lymphoma) Platelet count ≥50,000/μL (unless documented bone marrow involvement with lymphoma) At least 6 weeks from autologous stem cell transplantation At least 3 months from allogeneic stem cell transplantation and off immunosuppression and no evidence of graft versus host disease (GVHD) Previous treatment with brentuximab vedotin will be allowed if it was done 6 months prior to enrollment and patient was not refractory Measurable disease ≥1.5 cm seen on computed tomography (CT) scan and Fluorodeoxyglucose (FDG) avid disease on positron emission Tomography (PET) scan. Splenomegaly measuring >12 cm, if attributed to TCL and/or positive bone marrow involvement with lymphoma are also eligible. Females of childbearing potential must have a negative serum or urine pregnancy test result within 7 days prior to the first dose of study treatment. Women of child-bearing age must agree to use an effective contraception method during the study and for at least 6 months following the last dose of study drug. Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 6 months following the last dose of study drug. Subjects must have the ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Anaplastic large cell lymphoma (ALCL) both alk positive and negative Cutaneous T cell lymphomas except transformed Mycosis fungoides (MF) Prior treatment with Brentuximab in the last 6 months or previously refractory to Brentuximab Vedotin (BV) or had progressive disease (PD) while on BV Pregnancy or breast feeding women Prior malignancy within the past 3 years except non melanoma skin cancer or other localized cancer treated with curative intent Presence of grade >2 peripheral neuropathy or patients with the demyelinating form of Charcot-Marie-Tooth syndrome. Presence of central nervous system (CNS) involvement requiring active treatment History of progressive multifocal leukoencephalopathy (PML) Myocardial infarction within the past 6 months Patients with the following medical conditions that could affect their participation in the study: any active acute or chronic or uncontrolled infection liver disease including history of viral hepatitis B or C, evidence of cirrhosis, chronic active or persistent hepatitis a known history of HIV symptomatic cardiac disease, including congestive heart failure, coronary artery disease, and arrhythmias Prior hypersensitivity to any component in the ADC formulation Treatment with chemotherapy or investigational agents within 2 weeks of start of study treatment

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<br>Brentuximab vedotin 1.8 mg/kg intravenously (IV) once every 3 weeks | Drug: Brentuximab vedotin<br>* study drug given intravenously to determine efficacy in study diseases<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | The primary objective is to evaluate overall response rate (ORR). Overall response rate will be estimated by the total number of patients who achieve a CR and PR divided by the total number of evaluable patients. Response will be assessed using CT scans according to the revised Cheson criteria. CR is defined as complete resolution of all clinically detectable disease and disease related symptoms that were present prior to therapy PR is defined as at least 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses Patients should have completed at least 1 cycle of treatment to be evaluable for ORR. | Three years after end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response | Complete Response is defined as complete resolution of all clinically detectable disease and disease related symptoms that were present prior to therapy. A post-treatment residual mass of any size is permitted as long as it is PET negative. CR rate will be calculated by dividing the total number of patients who have achieved a complete response by the total number of evaluable patients. | Three years after end of treatment | 
| Progression Free Survival | Progression-free survival (PFS) is defined as the time from enrollment into the study to disease progression or death due to any cause. The distribution of PFS will be estimated using the Kaplan-Meier method. Disease progression may be defined as the date of documentation of a new lesion or enlargement of a previous lesion, or the date of the scheduled clinic visit immediately after radiologic assessment has been completed. For a patient who is alive without progression at the end of study follow-up, observation of PFS is censored on the date of last contact. | Three years after end of treatment | 
| Overall Survival | The overall survival (OS) is defined as the time from enrollment to the time of death due to any cause. For a patient who is alive at the end of study follow-up, observation of OS is censored on the date of last contact. The distribution of OS will be estimated using the Kaplan-Meier method. | Three years after end of treatment | 
| Duration of Response | Duration of response (DOR) is defined as the time from first documentation of objective tumor response (CR or PR) to the time to tumor progression or death due to any cause. | Three years after end of treatment | 
| Time to Treatment Failure | Time to treatment failure (TTF) is defined as the time from enrollment to discontinuation of treatment for any reason, including disease progression, treatment toxicity, and death | Up to 13 months after start of treatment | 
| Response Review | Responses will be reviewed by the investigator (PI or co-investigator) who is treating the patient at each participating site. | Three years after end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Leukemia, Brentuximab Vedotin