Back to resultsA Phase II Study of Single Agent Brentuximab Vedotin in Relapsed/Refractory CD30 Low (<10%) Mature T Cell Lymphoma (TCL)
Primary Purpose
T-cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Hepato-splenic T-cell Lymphoma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Brentuximab vedotin
Sponsored by
About this trial
This is an interventional treatment trial for T-cell Lymphoma focused on measuring Lymphoma, Leukemia, Brentuximab Vedotin
Eligibility Criteria
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
Sites / Locations
- University of Michigan
- Wayne State University, Karmanos Cancer InstituteRecruiting
- Hackensack University Medical Center
- University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
- Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Brentuximab vedotin
Arm Description
Brentuximab vedotin 1.8 mg/kg intravenously (IV) once every 3 weeks
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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
Response Review
Responses will be reviewed by the investigator (PI or co-investigator) who is treating the patient at each participating site.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02588651
Brief Title
A Phase II Study of Single Agent Brentuximab Vedotin in Relapsed/Refractory CD30 Low (<10%) Mature T Cell Lymphoma (TCL)
Official Title
A Phase II Study of Single Agent Brentuximab Vedotin in Relapsed/Refractory CD30 Low (<10%) Mature T Cell Lymphoma (TCL)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 17, 2016 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Deepa Jagadeesh
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
Keywords
Lymphoma, Leukemia, Brentuximab Vedotin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Brentuximab vedotin
Arm Type
Experimental
Arm Description
Brentuximab vedotin 1.8 mg/kg intravenously (IV) once every 3 weeks
Intervention Type
Drug
Intervention Name(s)
Brentuximab vedotin
Intervention Description
study drug given intravenously to determine efficacy in study diseases
Primary Outcome Measure Information:
Title
Overall Response Rate
Description
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.
Time Frame
Three years after end of treatment
Secondary Outcome Measure Information:
Title
Complete Response
Description
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.
Time Frame
Three years after end of treatment
Title
Progression Free Survival
Description
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.
Time Frame
Three years after end of treatment
Title
Overall Survival
Description
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.
Time Frame
Three years after end of treatment
Title
Duration of Response
Description
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.
Time Frame
Three years after end of treatment
Title
Time to Treatment Failure
Description
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
Time Frame
Up to 13 months after start of treatment
Title
Response Review
Description
Responses will be reviewed by the investigator (PI or co-investigator) who is treating the patient at each participating site.
Time Frame
Three years after end of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Deepa Jagadeesh, MD, MPH
Phone
1-866-223-8100
Email
TaussigResearch@ccf.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Deepa Jagadeesh, MD, MPH
Organizational Affiliation
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Paolo Caimi, MD
Organizational Affiliation
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-5413
Country
United States
Individual Site Status
Withdrawn
Facility Name
Wayne State University, Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erlene Seymour, MD
Email
seymoure@karmanos.org
First Name & Middle Initial & Last Name & Degree
Erlene Seymour, MD
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Individual Site Status
Completed
Facility Name
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Completed
Facility Name
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Deepa Jagadeesh, MD, MPH
Phone
866-223-8100
Email
TaussigResearch@ccf.org
12. IPD Sharing Statement
Learn more about this trial
A Phase II Study of Single Agent Brentuximab Vedotin in Relapsed/Refractory CD30 Low (<10%) Mature T Cell Lymphoma (TCL)
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