Clinical Trial Details
— Status: Active, not recruiting
Administrative data
NCT number |
NCT02663297 |
Other study ID # |
LCCC 1524-ATL |
Secondary ID |
R01HL114564 |
Status |
Active, not recruiting |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
July 15, 2016 |
Est. completion date |
January 2037 |
Study information
Verified date |
April 2024 |
Source |
UNC Lineberger Comprehensive Cancer Center |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
The body has different ways of fighting infection and disease. No single way seems perfect
for fighting cancer. This research study combines two different ways of fighting disease:
antibodies and T cells. Antibodies are proteins that protect the body from disease caused by
bacteria or toxic substances. Antibodies work by binding those bacteria or substances, which
stops them from growing and causing bad effects. T cells, also called T lymphocytes, are
special infection-fighting blood cells that can kill other cells, including tumor cells or
cells that are infected. Both antibodies and T cells have been used to treat patients with
cancers. They both have shown promise, but neither alone has been sufficient to cure most
patients. This study is designed to combine both T cells and antibodies to create a more
effective treatment. The treatment that is being researched is called autologous T lymphocyte
chimeric antigen receptor cells targeted against the CD30 antigen (ATLCAR.CD30)
administration.
In previous studies, it has been shown that a new gene can be put into T cells that will
increase their ability to recognize and kill cancer cells. A gene is a unit of DNA. Genes
make up the chemical structure carrying the patient's genetic information that may determine
human characteristics (i.e., eye color, height and sex). The new gene that is put in the T
cells in this study makes a piece of an antibody called anti-CD30. This antibody floats
around in the blood and can detect and stick to cancer cells called lymphoma cells because
they have a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been
used to treat people with lymphoma, but have not been strong enough to cure most patients.
For this study, the anti-CD30 antibody has been changed so that instead of floating free in
the blood part of it is now joined to the T cells. Only the part of the antibody that sticks
to the lymphoma cells is attached to the T cells instead of the entire antibody. When an
antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30
chimeric (combination) receptor-activated T cells seem to kill some of the tumor, but they do
not last very long in the body and so their chances of fighting the cancer are unknown.
The purpose of this research study is to determine a safe dose of the ATLCAR.CD30 cells that
can be given to subjects after undergoing an autologous transplant. This is the first step in
determining whether giving ATLCAR.CD30 cells to others with lymphoma in the future will help
them. The researchers also want to find out what side effects patients will have after they
receive the ATLCAR.CD30 cells post-transplant. This study will also look at other effects of
ATLCAR.CD30 cells, including their effect on your cancer and how long they will survive in
your body.
Description:
STUDY OBJECTIVES
Primary Objective
- To determine the safety and tolerability and to estimate the MTD of ATLCAR.CD30 post
ASCT in patients with CD30+ lymphoma at high risk for relapse
Secondary Objectives
- To measure the survival of ATLCAR.CD30 in vivo
- To estimate PFS after infusion of ATLCAR.CD30 post ASCT in patients with CD30+ lymphoma
at high risk for relapse
- To determine the overall survival after infusion of ATLCAR.CD30 post ASCT in patients
with CD30+ lymphoma at high risk for relapse
Exploratory Objective
- To measure patient-reported symptom, physical function, and health-related quality of
life at baseline and over time in patients treated with ATLCAR.CD30 cells.
ENDPOINTS
Primary Endpoint
- Toxicity will be classified and graded according to the National Cancer Institute's
Common Terminology Criteria for Adverse Events (CTCAE, version 4.0) and CRS toxicity
will be graded according to the toxicity scale outlined in 11.6 (Appendix F: CRS
Toxicity Grading Scale and Management Guidelines). The MTD will be based on the rate of
dose-limiting toxicity
Secondary (Clinical) Endpoint
- PFS is defined from day of ASCT to relapse (in subjects with a documented complete
response after ASCT) or progression (in subjects with documented stable disease or
partial response after ASCT), or death as a result of any cause as per the Revised
Response Criteria for Malignant Lymphoma.
- Overall survival will be measured from the date of administration of CAR.CD30 transduced
ATL to date of death
- Persistence of CAR.CD30 T cells in vivo will be determined by quantitative PCR and flow
cytometry in peripheral blood samples.
Exploratory Endpoint
- Patient reported symptoms will be measured using selected symptoms from the NCI
PRO-CTCAE. Patient-reported physical function will be measured using the PROMIS Physical
Function Score derived from the PROMIS Physical Function Short Form 20a v1.0.
Patient-reported health-related quality of life will be measured using the PROMIS Global
Health Score derived from the PROMIS Global Health Short Form v1.0-1.1.
OUTLINE
Patients scheduled to undergo an autologous stem cell transplantation (ASCT) for treatment of
lymphoma will be approached for consent to screening and potential enrollment into LCCC1524.
Peripheral blood cells will be collected from consenting patients who meet eligibility for
cell procurement for creation of ATLCAR.CD30 cells prior to ASCT. The ASCT, including
mobilization and collection of PBSCs, administration of myeloablative therapy, reinfusion of
PBSCs and supportive care following transplant will be as per routine standard of care, and
not expected to be impacted by enrollment into LCCC1524. Post ASCT, patients who meet
eligibility criteria for treatment will receive one infusion of ATLCAR.CD30 cells once there
is evidence of hematologic recovery. Research personnel will keep track of any patients who
undergo procurement but do not undergo treatment with ATLCAR.CD30 cells, and the reason for
withholding treatment.
Cell Procurement
Peripheral blood, up to 300 mL total (in up to 3 collections) will be obtained for subjects
for cell procurement. In patients with low (CD3 count as assayed by flow cytometry less than
200/μl) T-cell count in the peripheral blood, a leukopheresis may be performed to isolate
sufficient T cells. The parameters for pheresis will be up to 2 blood volumes.
For pediatric patients (patients under 18 years of age), the total amount of blood drawn will
not be more than 3 mL (less than 1 teaspoon per 2.2 lbs. that the child weighs.
ATLCAR.CD30 Cells Administration
Post ASCT, once the patient has started to experience hematologic recovery (defined as ANC
≥500 cells/mm3 for 3 consecutive days, AND platelet count ≥25 cells/mm3 without transfusion
over the preceding 5 days, AND Hg ≥8g/dL without transfusion support over preceding 5 days),
ATLCAR.CD30 cells will be admnistered. This will generally occur between 14 and 20 days
following infusion of autologous stem cells following high-dose chemotherapy.
Duration of Therapy
Therapy in LCCC1524 involves just one infusion of ATLCAR.CD30 cells. Treatment with one
infusion will be administered unless:
- Patient decides to withdraw from study treatment, OR
- General or specific changes in the patient's condition render the patient unacceptable
for further treatment in the judgment of the investigator.
Duration of Follow-Up
Patients will be followed for up to 15 years or until death, whichever occurs first. Patients
removed from study for unacceptable adverse events will be followed until resolution or
stabilization of the adverse event.