BV-CHEP Chemotherapy for Adult T-cell Leukemia or Lymphoma
brief summary
Adult T-cell leukemia/lymphoma (ATLL) is a rare form of cancer found mostly among people from the Caribbean islands, Western Africa, Brazil, Iran, and Japan. Most cases of this disease in the United States occur along the East Coast due to emigration from the Caribbean islands. There is currently no standard treatment for ATLL. Research shows that patients who go into first time remission (respond completely or partially to treatment) and have a bone marrow transplant have the best outcomes. Traditional chemotherapy treatments have generally not worked well in patients with ATLL. Additionally, not all patients will be eligible for a bone marrow transplant. The purpose of this study is to see how well individuals with ATLL respond to an investigational cancer treatment. This investigational treatment combines a drug called brentuximab vedotin with a standard chemotherapy treatment made up of cyclophosphamide, doxorubicin, etoposide, and prednisone. This treatment is considered investigational because it is not approved by the United States Food and Drug Administration (FDA) for the treatment of ATLL. Brentuximab vedotin, also known as Adcetris, is approved by the United States Food and Drug Administration (FDA) for treatment of certain types of lymphomas, including peripheral T-cell lymphomas when combined with cyclophosphamide, doxorubicin, and prednisone in patients whose cancer cells express a type of marker called CD30. Brentuximab vedotin is an antibody that also has a chemotherapy drug attached to it. Antibodies are proteins that are part of the immune system. They can stick to and attack specific targets on cancer cells. The antibody part of brentuximab vedotin sticks to a target called cluster of differentiation 30 (CD30) that is located on the outside of the cancer cells. Normal cells have little or no CD30 on their surface. ATLL cancer cells often have a larger amount of CD30 on their surface than normal cells. However, CD30 is found in different amounts on ATLL cancer cells. This study will also test the amount of CD30 found on each participant's cancer cells. Researchers will be looking to see if the response to the study treatment varies based on the amount of CD30 found on the outside participants' cancer cells. In another study, brentuximab vedotin was combined in another study with cyclophosphamide, doxorubicin, and prednisone. The study included patients with various types of T-cell lymphomas. Two of the patients enrolled in that study had ATLL. Both had a complete response (no evidence of disease). The researchers in this study (LCCC 1637) have added etoposide to the combination of brentuximab vedotin with cyclophosphamide, doxorubicin, and prednisone. They predict that the addition of etoposide will improve patient outcomes. Research shows that etoposide helps improve outcomes in patients with certain types of T-cell lymphomas who undergo chemotherapy treatment. This investigational combination of brentuximab vedotin with cyclophosphamide, doxorubicin, etoposide, and prednisone is called BV-CHEP.
detailed description
STUDY OBJECTIVES
Primary Objective To define the proportion of subjects with CR after 4-6 cycles of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, etoposide, and prednisone (BV-CHEP) in the treatment of adult T-cell leukemia/lymphoma.
Secondary Objectives
To estimate the overall response rate (ORR) with 4-6 cycles of BV-CHEP therapy in patients with adult T-cell leukemia/lymphoma.
To determine progression-free survival (PFS) for BV-CHEP in patients with adult T-cell leukemia/lymphoma who received or did not receive BV maintenance.
To determine duration of response to BV-CHEP in patients with adult T-cell leukemia/lymphoma who received or did not receive BV maintenance.
To determine overall survival (OS) of patients with adult T-cell leukemia/lymphoma treated with BV-CHEP who received or did not receive BV maintenance therapy.
To evaluate the toxicity and tolerability of BV-CHEP and BV maintenance therapy via the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03).
\*Note: After completion or withdrawal from BV-CHEP therapy, patients will segregate into one of the following groups: 1) those who progressed on BV-CHEP; 2) those who completed 4-6 cycles of BV-CHEP and went on to allogeneic transplant; 3) those who completed 6 cycles of BV-CHEP but were CD30 negative and ineligible for maintenance therapy; and 4) those who completed 6 cycles of BV-CHEP, were CD30 positive, but continued study treatment on BV in the maintenance phase of the study.
ENDPOINTS
Primary Endpoint
Criteria for CR after 4-6 cycles of BV-CHEP will be based on the International Workshop to standardize response criteria for malignant lymphomas (ie, Lugano Criteria per Cheson, et al. J Clin Oncol. 2014;32(27):3059-68).
Secondary Endpoints
Criteria for overall response will be based on the International Workshop to standardize response criteria for malignant lymphomas (ie, Lugano Criteria per Cheson, et al. J Clin Oncol. 2014;32(27):3059-68).
official title
Brentuximab Vedotin With Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (BV-CHEP) for the Treatment of Adult T-Cell Leukemia/Lymphoma: A Pilot Study of the Rare Lymphoma Working Group