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

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ClinicalTrials.gov Identifier: NCT02588651
Recruitment Status : Recruiting
First Posted : October 28, 2015
Last Update Posted : August 9, 2018
Sponsor:
Information provided by (Responsible Party):
Deepa Jagadeesh, Case Comprehensive Cancer Center

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.


Condition or disease Intervention/treatment Phase
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 Transformed Mycosis Fungoides Drug: Brentuximab vedotin Phase 2

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)

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 31 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Single Agent Brentuximab Vedotin in Relapsed/Refractory CD30 Low (<10%) Mature T Cell Lymphoma (TCL)
Actual Study Start Date : June 17, 2016
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: Brentuximab vedotin
Brentuximab vedotin 1.8 mg/kg intravenously (IV) once every 3 weeks
Drug: Brentuximab vedotin
study drug given intravenously to determine efficacy in study diseases




Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Three years after end of treatment ]

    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 :
  1. Complete Response [ Time Frame: Three years after end of treatment ]
    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.

  2. Progression Free Survival [ Time Frame: Three years after end of treatment ]
    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.

  3. Overall Survival [ Time Frame: Three years after end of treatment ]
    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.

  4. Duration of Response [ Time Frame: Three years after end of treatment ]
    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.

  5. Time to Treatment Failure [ Time Frame: Up to 13 months after start of treatment ]
    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

  6. Response Review [ Time Frame: Three years after end of treatment ]
    Responses will be reviewed by the investigator (PI or co-investigator) who is treating the patient at each participating site.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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), and transformed mycosis fungoides
  • 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 (PE) scan
  • 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
  • Current therapy with chemotherapy or investigational agents within 4 weeks of start of study treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02588651


Contacts
Contact: Deepa Jagadeesh, MD, MPH 216-444-0857 jagaded@ccf.org

Locations
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109-5413
Contact: Ryan Wilcox, MD       rywilcox@umich.edu   
Principal Investigator: Ryan Wilcox, MD         
Wayne State University, Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Radhakrishnan Ramchandren, MD    313-576-8739    ramchanr@karmanos.org   
Principal Investigator: Radhakrishnan Ramchandren, MD         
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Tatyana Feldman, MD    551-996-5900    Tatyana.Feldman@HackensackMeridian.org   
Principal Investigator: Tatyana Feldman, MD         
United States, Ohio
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Paolo Caimi, MD    216-844-0139    Paolo.Caimi@uhhospitals.org   
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Deepa Jagadeesh, MD, MPH    216-444-0857    jagaded@ccf.org   
Sponsors and Collaborators
Deepa Jagadeesh
Investigators
Principal Investigator: Deepa Jagadeesh, MD, MPH Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Principal Investigator: Paolo Caimi, MD Case Medica Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Responsible Party: Deepa Jagadeesh, Principal Investigator, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT02588651     History of Changes
Other Study ID Numbers: CASE1415
First Posted: October 28, 2015    Key Record Dates
Last Update Posted: August 9, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Deepa Jagadeesh, Case Comprehensive Cancer Center:
Lymphoma
Leukemia
Brentuximab Vedotin

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Mycoses
Mycosis Fungoides
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Immunoblastic Lymphadenopathy
Intestinal Diseases
Enteropathy-Associated T-Cell Lymphoma
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell, Cutaneous
Leukemia, Lymphoid
Leukemia
Lymphadenopathy
Gastrointestinal Diseases
Digestive System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs