Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT03264131 |
Other study ID # |
LCCC1637 |
Secondary ID |
|
Status |
Active, not recruiting |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
October 15, 2018 |
Est. completion date |
December 15, 2028 |
Study information
Verified date |
September 2023 |
Source |
UNC Lineberger Comprehensive Cancer Center |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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.
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).
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:
- They are not eligible for a bone marrow transplant,
- Their cancer cells tested positive for CD30, and
- Their cancer has not gotten worse after taking BV-CHEP.
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.