A Phase 2 interventional study of Brentuximab Vedotin and CHEP in Lymphoma, Adult T-Cell Leukemia/Lymphoma and Lymphatic Diseases, sponsored by UNC Lineberger Comprehensive Cancer Center. Completed at 4 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-29.
Sponsored by UNC Lineberger Comprehensive Cancer Center · Phase 2, Interventional, and Treatment
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.
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).
PFS is defined as time from D1 of treatment until disease progression (based on Lugano criteria) or death from any cause.
Duration of response is defined as the time from documentation of tumor response per Lugano criteria to disease progression
OS is defined as the time from D1 of treatment until death from any cause
Toxicity and tolerability of therapy will be assessed via the NCI CTCAE v4.03
TREATMENT INFORMATION
Patients will undergo screening to see if they are eligible. If eligible, participants will start by receiving 2 cycles of BV-CHEP (cycles 1 and 2). After 2 cycles of BV-CHEP, participants will have a positron emission tomography/computed tomography (PET/CT) or a CT scan to assess their disease. If the scan shows the cancer has stayed the same or gotten better, participants may continue taking BV-CHEP for two more cycles (cycle 3 and 4). If, at any time during study treatment, a participant's disease gets worse, the participant will end study treatment and other treatment options will be discussed with you.
If a participant continues on BV-CHEP, at the beginning of cycle 5, the participant will have a PET/CT scan. If the cancer has gotten better and the participant is eligible for a bone marrow transplant, he/she will have the transplant. If the participant is not eligible for a bone marrow transplant and the cancer has stayed the same or gotten better, the participant may continue on BV-CHEP for two more cycles (cycles 5 and 6).
At the end of cycle 6 of BV-CHEP, participants will have another PET/CT scan. If the scan shows the cancer has gotten better and the participant is eligible for a bone marrow transplant, he/she will have the transplant. If a participant is not eligible for a bone marrow transplant and his/her cancer cells did not test positive for CD30, the participant will end study treatment. The study doctor will discuss other treatment options that are not part of this study with the participant.
Participants may continue on brentuximab vedotin alone as maintenance therapy if:
Participants will be removed from BV maintenance therapy if their cancer get worse.
DURATION OF THERAPY Therapy in LCCC 1637 involves up to 6 cycles of treatment with brentuximab vedotin (BV) with a chemotherapy treatment made up of cyclophosphamide, doxorubicin, etoposide, and prednisone (CHEP). Each cycle is 21 days long. Participants may continue on BV alone as maintenance therapy after 6 cycles of BV-CHEP if they meet the requirements outlined above. Each cycles of BV maintenance therapy is 21-day long. BV maintenance therapy may continue until a participant's disease progresses.
DURATION OF FOLLOW-UP PERIOD Participants will be followed for survival for up to 5 years. They will also have a PET/CT or CT scan and a blood test every 6 months for 2 years after study treatment ends.
Subjects must meet all of the following inclusion criteria to participate in this study:
Histological confirmation of biopsy-proven peripheral T-cell leukemia/lymphoma consistent with ATLL
Demonstrate adequate organ function as defined below; all screening labs to be obtained within three days prior to study treatment.
System: Renal -Calculated creatinine clearance
Laboratory Value: ≥ 30 mL/min using the Cockcroft-Gault formula for subjects with creatinine levels > 2.0 x institutional ULN
System: Hepatic - Bilirubin
Laboratory Value: ≤ 3.0 mg/dL
System: Hepatic - Aspartate aminotransferase (AST)
Laboratory Value: ≤ 2.5 × ULN
System: Hepatic - Alanine aminotransferase (ALT)
Laboratory Value: ≤ 2.5 × ULN
Exclusion Criteria:
Subjects who meet any of the following criteria should be excluded from study participation:
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 2 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 · Drug: CHEP
Brentuximab Vedotin will be given at 1.8 mg/kg IV over approximately 30 minutes on D1 every 21 days for 2-6 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 2-6 cycles Doxorubicin- 50 mg/m\^2 IV over approximately 3-5 minutes on D1 every 21 days for 2-6 cycles. Etoposide - 100 mg/m\^2 IV over approximately 1 hour each day for 3 days every 21 days for 2-6 cycles. Prednisone - 100 mg, orally once daily for 5 days every 21 days for 2-6 cycles.
Complete Response Rate After 2-6 Cycles of Brentuximab Vedotin in Combination With Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (BV-CHEP)
The response was assessed based on the International Workshop to standardize response criteria for malignant lymphomas (i.e., Lugano Criteria per Cheson, et al. J Clin Oncol. 2014;32(27):3059-68; Complete Response: Positron emission tomography (PET): Complete metabolic response Computerized tomography (CT): Target must regress to ≤ 1.5 cm in the largest transverse diameter (LDi) or no extra lymphatic sites of disease. Partial Response: PET: reduced uptake compared with baseline, and CT: ≥50% decrease in the sum of the products of diameters (SPD).No Response or Stable Disease: No metabolic response on PET or \< 50% decrease from baseline in SPD of up to 6 dominant, measurable nodes and extra nodal sites on CT. Progressive Disease: PET: Score 4 or 5 with an increase in the intensity of uptake or CT: an individual node/lesion must be abnormal with LDi \> 1.5 cm, increase by ≥ 50% from the cross product of the LDi and shortest axis perpendicular to LDi (SDi).
Time frame: 18 weeks
Overall Response Rate (ORR) Associated With 2-6 Cycles of BV-CHEP Therapy in Patients With Adult T-Cell Leukemia/Lymphoma.
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
Time frame: Up to 24 months
Progression-free Survival (PFS) for BV-CHEP in Patients With Adult T-cell Leukemia/Lymphoma
PFS is assessed from day 1 of treatment until disease progression (based on International Workshop to standardize response criteria for malignant lymphomas (i.e. Lugano Criteria) or death. Progression Free Survival (PFS) is calculated from the date of randomization to the date of progression or the date of death from any cause. The median PFS is estimated using the Kaplan-Meier method. The Measure of Dispersion reported is the Full Range, representing the minimum and maximum observed follow-up time (whether censored or event occurred) for all participants in this group.
Time frame: Up to 15.2 months
Duration of Response to BV-CHEP in Patients With Adult T-cell Leukemia/Lymphoma
Duration of response is defined as the time from documentation of tumor response per Lugano criteria to disease progression. Subjects with a leukemic component to their disease at baseline will have peripheral blood assessed per adult T-cell leukemia/lymphoma NCCN Guidelines version 2.2017
Time frame: Up to 24 months
Overall Survival (OS) of Patients With Adult T-cell Leukemia/Lymphoma Treated With BV-CHEP Who Received or Did Not Receive BV Maintenance Therapy.
Overall survival is defined as the time from date of randomization until death from any cause. The median OS is estimated using the Kaplan-Meier method. The Measure of Dispersion reported is the Full Range, representing the minimum and maximum observed follow-up time (whether censored or event occurred) for all participants in this group. BV maintenance was not reported because only one patient received it, and only for a limited number of dose.
Time frame: Up to 68 months
BV-CHEP and BV Maintenance Therapy-Attributed Grade ≥3 Adverse Events Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4)
Toxicity and tolerability of therapy will be assessed via the NCI CTCAE v4.03, a scale from 1-mild to 5-death.Only treatment-attributed Grade ≥3 adverse events were included.
Time frame: Up to 24 months
Progression-free Survival (PFS) for BV Maintenance
PFS will be measured from day 1 of treatment to disease progression (per the Lugano Criteria) or death. BV maintenance was minimal, with only one patient receiving a limited number of doses. The single analyzed participant experienced disease progression during the study period. Number of participant showed no progression is reported.
Time frame: Up to Day 309
Participants were enrolled in the study between 10/11/2018 - 06/22/2022 at four cancer centers in the United States.
| Milestone | Open-label, Multicenter, Single-Arm |
|---|---|
| Started | 16 |
| Completed | 16 |
| Not completed | 0 |
The response was assessed based on the International Workshop to standardize response criteria for malignant lymphomas (i.e., Lugano Criteria per Cheson, et al. J Clin Oncol. 2014;32(27):3059-68; Complete Response: Positron emission tomography (PET): Complete metabolic response Computerized tomography (CT): Target must regress to ≤ 1.5 cm in the largest transverse diameter (LDi) or no extra lymphatic sites of disease. Partial Response: PET: reduced uptake compared with baseline, and CT: ≥50% decrease in the sum of the products of diameters (SPD).No Response or Stable Disease: No metabolic response on PET or \< 50% decrease from baseline in SPD of up to 6 dominant, measurable nodes and extra nodal sites on CT. Progressive Disease: PET: Score 4 or 5 with an increase in the intensity of uptake or CT: an individual node/lesion must be abnormal with LDi \> 1.5 cm, increase by ≥ 50% from the cross product of the LDi and shortest axis perpendicular to LDi (SDi).
| Participants | Open-label, Multicenter, Single-Arm |
|---|---|
| Complete Response | 10 |
| Partial Response | 4 |
| Progressive Disease | 2 |
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
| Participants | Open-label, Multicenter, Single-Arm |
|---|---|
| Overall Response Rate (ORR) Associated With 2-6 Cycles of BV-CHEP Therapy in Patients With Adult T-Cell Leukemia/Lymphoma. | 14 |
PFS is assessed from day 1 of treatment until disease progression (based on International Workshop to standardize response criteria for malignant lymphomas (i.e. Lugano Criteria) or death. Progression Free Survival (PFS) is calculated from the date of randomization to the date of progression or the date of death from any cause. The median PFS is estimated using the Kaplan-Meier method. The Measure of Dispersion reported is the Full Range, representing the minimum and maximum observed follow-up time (whether censored or event occurred) for all participants in this group.
| months | Open-label, Multicenter, Single-Arm |
|---|---|
| Progression-free Survival (PFS) for BV-CHEP in Patients With Adult T-cell Leukemia/Lymphoma | 7.11 (0.7 to 15.2) |
Duration of response is defined as the time from documentation of tumor response per Lugano criteria to disease progression. Subjects with a leukemic component to their disease at baseline will have peripheral blood assessed per adult T-cell leukemia/lymphoma NCCN Guidelines version 2.2017
| months | Open-label, Multicenter, Single-Arm |
|---|---|
| Duration of Response to BV-CHEP in Patients With Adult T-cell Leukemia/Lymphoma | 3.84 (0.76 to 12.46) |
Overall survival is defined as the time from date of randomization until death from any cause. The median OS is estimated using the Kaplan-Meier method. The Measure of Dispersion reported is the Full Range, representing the minimum and maximum observed follow-up time (whether censored or event occurred) for all participants in this group. BV maintenance was not reported because only one patient received it, and only for a limited number of dose.
| months | Open-label, Multicenter, Single-Arm |
|---|---|
| Overall Survival (OS) of Patients With Adult T-cell Leukemia/Lymphoma Treated With BV-CHEP Who Received or Did Not Receive BV Maintenance Therapy. | 15.7 (3.3 to 68) |
Toxicity and tolerability of therapy will be assessed via the NCI CTCAE v4.03, a scale from 1-mild to 5-death.Only treatment-attributed Grade ≥3 adverse events were included.
| Participants | Open-label, Multicenter, Single-Arm |
|---|---|
| Anemia | 7 |
| Febrile neutropenia | 6 |
| Abdominal pain | 1 |
| Esophagitis | 1 |
| Mucositis oral | 3 |
| Nausea | 1 |
| Typhlitis | 1 |
| Vomiting | 1 |
| colitis | 1 |
| Lymphocyte count decreased | 3 |
| Neutrophil count decreased | 5 |
| Platelet count decreased | 4 |
| White blood cell decreased | 5 |
| Hypokalemia | 1 |
| Hyponatremia | 1 |
| Dyspnea | 1 |
| Sore throat | 1 |
| Hypotension | 1 |
PFS will be measured from day 1 of treatment to disease progression (per the Lugano Criteria) or death. BV maintenance was minimal, with only one patient receiving a limited number of doses. The single analyzed participant experienced disease progression during the study period. Number of participant showed no progression is reported.
| Participants | Open-label, Multicenter, Single-Arm |
|---|---|
| Progression-free Survival (PFS) for BV Maintenance | 0 |
Collected over Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. (Up to 68 months).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Open-label, Multicenter, Single-Arm | 12/16 (75%) | 7/16 (43.8%) | 9/16 (56.3%) |
| Event | Open-label, Multicenter, Single-Arm |
|---|---|
| Febrile neutropeniaBlood and lymphatic system disorders | 2/16 |
| General disorders and administration site conditions - Other, specifyGeneral disorders | 2/16 |
| Infections and infestations - Other, specifyInfections and infestations | 2/16 |
| Hearing impairedEar and labyrinth disorders | 1/16 |
| Eye painEye disorders | 1/16 |
| ConstipationGastrointestinal disorders | 1/16 |
| Mucositis oralGastrointestinal disorders | 1/16 |
| TyphlitisGastrointestinal disorders | 1/16 |
| VomitingGastrointestinal disorders | 1/16 |
| FatigueGeneral disorders | 1/16 |
| Event | Open-label, Multicenter, Single-Arm |
|---|---|
| AnemiaBlood and lymphatic system disorders | 7/16 |
| NauseaGastrointestinal disorders | 7/16 |
| Mucositis oralGastrointestinal disorders | 6/16 |
| ChillsGeneral disorders | 6/16 |
| HeadacheNervous system disorders | 6/16 |
| Abdominal painGastrointestinal disorders | 5/16 |
| DiarrheaGastrointestinal disorders | 5/16 |
| DizzinessNervous system disorders | 5/16 |
| FatigueGeneral disorders | 4/16 |
| Investigations - Other, specifyInvestigations | 4/16 |
Participants consented and started the study.
| Age, Continuous(years) | Open-label, Multicenter, Single-Arm |
|---|---|
| Median | 56 (43.75 to 65.50) |
| Sex: Female, Male(Participants) | Open-label, Multicenter, Single-Arm |
|---|---|
| Female | 12 |
| Male | 4 |
| Ethnicity (NIH/OMB)(Participants) | Open-label, Multicenter, Single-Arm |
|---|---|
| Hispanic or Latino | 1 |
| Not Hispanic or Latino | 15 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Open-label, Multicenter, Single-Arm |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 14 |
| White | 0 |
| More than one race | 0 |
| Unknown or Not Reported | 1 |
| Region of Enrollment(participants) | Open-label, Multicenter, Single-Arm |
|---|---|
| United States | 16 |
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