Clinical trial NCT02588651: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2015-10-28
Enrollment: 23
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: 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)

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

Primary outcomes:
measure: Overall Response Rate
timeFrame: Three years after end of treatment
Secondary outcomes:
measure: Complete Response
timeFrame: Three years after end of treatment
measure: Progression Free Survival
timeFrame: Three years after end of treatment
measure: Overall Survival
timeFrame: Three years after end of treatment
measure: Duration of Response
timeFrame: Three years after end of treatment
measure: Time to Treatment Failure
timeFrame: Up to 13 months after start of treatment
measure: Response Review
timeFrame: Three years after end of treatment
Other outcomes:
Locations:
city: Detroit
country: United States
facility: Wayne State University, Karmanos Cancer Institute
state: Michigan
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
name: Deepa Jagadeesh, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
name: Paolo Caimi, MD
role: PRINCIPAL_INVESTIGATOR
References: