BV-CHEP Chemotherapy for Adult T-cell Leukemia or Lymphoma
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|ClinicalTrials.gov Identifier: NCT03264131|
Recruitment Status : Recruiting
First Posted : August 28, 2017
Last Update Posted : April 26, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma Adult T-Cell Leukemia/Lymphoma Lymphatic Diseases||Drug: Brentuximab Vedotin Drug: CHEP||Phase 2|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||28 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Brentuximab Vedotin With Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (BV-CHEP) for the Treatment of Adult T-Cell Leukemia/Lymphoma: A Phase II Trial of the Rare Lymphoma Working Group|
|Actual Study Start Date :||October 15, 2018|
|Estimated Primary Completion Date :||January 30, 2021|
|Estimated Study Completion Date :||January 30, 2026|
Experimental: Open-label, Multicenter, Single-Arm
This is a single-arm intervention where patients will receive concurrent therapy with BV+CHEP [(brentuximab vedotin; 1.8 mg/kg IV, on D1 every 21 days) (cyclophosphamide 750 mg/m^2 on D1; doxorubicin 50 mg/m^2 on D1, etoposide 100 mg/m^2 IV infusion on D1-3; prednisone 100 mg orally once daily on D1-5; cycle length every 21 days)] for 4 to 6 cycles of induction therapy. After 6 cycles of BV + CHEP, responders (CR, PR or SD) who are not eligible for BMT and have CD30-positive ATLL will continue maintenance therapy with BV alone (1.8 mg/kg IV, every 21 days) until disease progression, withdrawal due to toxicity or death.
Drug: Brentuximab Vedotin
Brentuximab Vedotin will be given at 1.8 mg/kg IV over approximately 30 minutes on D1 every 21 days for 4-6 cycles. Responders (CR, PR or SD) who are not eligible for bone marrow transplant (BMT) and have CD30-positive ATLL will continue maintenance therapy with BV alone (1.8 mg/kg IV for approximately 30 minutes, every 21 days).
Cyclophosphamide- 750 mg/m^2 IV over approximately 1 hour on D1 every 21 days for 4-6 cycles
Doxorubicin- 50 mg/m^2 IV over approximately 3-5 minutes on D1 every 21 days for 4-6 cycles.
Etoposide - 100 mg/m^2 IV over approximately 1 hour each day for 3 days every 21 days for 4-6 cycles.
Prednisone - 100 mg, orally once daily for 5 days every 21 days for 4-6 cycles.
- Proportion of subjects with Complete Response after 4-6 cycles of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, etoposide, and prednisone (BV-CHEP) [ Time Frame: 18 weeks ]Criteria for CR after 4-6 cycles of BV-CHEP will be based on the International Workshop to standardize response criteria for malignant lymphomas (i.e. Lugano Criteria).
- Overall response rate (ORR) associated with 4-6 cycles of BV-CHEP therapy in patients with adult T-Cell leukemia/lymphoma. [ Time Frame: 70 weeks ]ORR will be evaluated as the rate of complete responses (CR) + partial responses (PR) as defined by the International Workshop to standardize response criteria for malignant lymphomas (i.e. Lugano Criteria). Patients with leukemic component to their disease at baseline will be assessed per Adult T-Cell Leukemia/Lymphoma National Comprehensive Cancer Network (NCCN) guidelines version 2.2017
- Progression-free survival (PFS) for BV-CHEP in patients with adult T-cell leukemia/lymphoma who received or did not receive BV maintenance. [ Time Frame: 3 years ]PFS will be assessed from day 1 of treatment until disease progression (based on International Workshop to standardize response criteria for malignant lymphomas (i.e. Lugano Criteria).
- Duration of response to BV-CHEP in patients with adult T-cell leukemia/lymphoma who received or did not receive BV maintenance. [ Time Frame: 3 years ]Duration of response is defined as the time from documentation of tumor response per Lugano criteria to disease progression.
- Overall survival (OS) of patients with adult T-cell leukemia/lymphoma treated with BV-CHEP who received or did not receive BV maintenance therapy. [ Time Frame: 3 years ]Overall survival is defined as the time from day 1 of treatment until death from any cause.
- Toxicity and tolerability of BV-CHEP and BV maintenance therapy via National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4) [ Time Frame: 70 weeks ]Toxicity and tolerability of therapy will be assessed via the NCI CTCAE v4.03
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): NCT03264131
|Contact: Bob Broomeremail@example.com|
|Contact: Jen Reedfirstname.lastname@example.org|
|United States, Massachusetts|
|Boston Medical Center||Recruiting|
|Boston, Massachusetts, United States, 02118|
|Contact: Mark Sloan, MD 617-638-2367 email@example.com|
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Bob Broomer 919-966-9257 firstname.lastname@example.org|
|Principal Investigator:||Dittus Christopher, DO, MPH||UNC Lineberger Comprehensive Cancer Center|