Administration of T Lymphocytes for Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma (CART CD30)
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 4/6/2019 |
| Start Date: | October 3, 2011 |
| End Date: | December 31, 2030 |
Phase I Study of the Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor for Relapsed CD30+ Hodgkin's Lymphoma and CD30+ Non-Hodgkin's Lymphoma (CART CD30)
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 diseases caused by
germs or toxic substances. They work by binding those germs 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 with germs. Both antibodies and T cells have been used to treat patients with
cancers: they both have shown promise, but have not been strong enough to cure most patients.
Investigators hope that both will work better together.
Investigators have found from previous research that they can put a new gene into T cells
that will make them recognize cancer cells and kill them. Investigators now want to see if
they can attach a gene to T cells that will help them do a better job at recognizing and
killing lymphoma cells.
The new gene that investigators will put in T cells makes an antibody called anti-CD30. This
antibody sticks to lymphoma cells because of 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 it is now joined to the T cells. When an antibody is joined to a T cell in this
way, it is called a chimeric receptor. These CD30 chimeric receptor-activated T cells seem to
kill some of the tumor, but they don't last very long and so their chances of fighting the
cancer are unknown.
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 diseases caused by
germs or toxic substances. They work by binding those germs 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 with germs. Both antibodies and T cells have been used to treat patients with
cancers: they both have shown promise, but have not been strong enough to cure most patients.
Investigators hope that both will work better together.
Investigators have found from previous research that they can put a new gene into T cells
that will make them recognize cancer cells and kill them. Investigators now want to see if
they can attach a gene to T cells that will help them do a better job at recognizing and
killing lymphoma cells.
The new gene that investigators will put in T cells makes an antibody called anti-CD30. This
antibody sticks to lymphoma cells because of 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 it is now joined to the T cells. When an antibody is joined to a T cell in this
way, it is called a chimeric receptor. These CD30 chimeric receptor-activated T cells seem to
kill some of the tumor, but they don't last very long and so their chances of fighting the
cancer are unknown.
When the patient enrolls on this study, they will be assigned a dose of CD30 chimeric
receptor-activated T cells. The dose level of cells that they will receive will not be based
on a medical determination of what is best for the patient, instead the dose is based on the
order in which the patient enrolled on the study relative to other participants. Subjects
enrolled earlier in the study will receive a lower dose of cells than those enrolled later in
the study. The risks of harm and discomfort from the study treatment may bear some
relationship to the dose level. The potential for direct benefit, if any, may also vary with
the dose level.
The patient will be given an injection of CD30 chimeric receptor-activated T cells into the
vein through an IV line at the assigned dose. The injection will take 1-10 minutes.
Investigators will follow the subject in the clinic after the injection for up to 4 hours.
To learn more about the way the CD30 chimeric receptor-activated T cells are working and how
long they last in the body, extra blood will be drawn.
If the patient has stable disease (the lymphoma did not grow) or there is a reduction in the
size of the lymphoma on imaging studies after the T-cell infusion, s/he can receive up to six
additional doses of the T cells at 8 to 12 weeks intervals if s/he wishes. After each T-cell
infusion, s/he will be monitored as described above.
receptor-activated T cells. The dose level of cells that they will receive will not be based
on a medical determination of what is best for the patient, instead the dose is based on the
order in which the patient enrolled on the study relative to other participants. Subjects
enrolled earlier in the study will receive a lower dose of cells than those enrolled later in
the study. The risks of harm and discomfort from the study treatment may bear some
relationship to the dose level. The potential for direct benefit, if any, may also vary with
the dose level.
The patient will be given an injection of CD30 chimeric receptor-activated T cells into the
vein through an IV line at the assigned dose. The injection will take 1-10 minutes.
Investigators will follow the subject in the clinic after the injection for up to 4 hours.
To learn more about the way the CD30 chimeric receptor-activated T cells are working and how
long they last in the body, extra blood will be drawn.
If the patient has stable disease (the lymphoma did not grow) or there is a reduction in the
size of the lymphoma on imaging studies after the T-cell infusion, s/he can receive up to six
additional doses of the T cells at 8 to 12 weeks intervals if s/he wishes. After each T-cell
infusion, s/he will be monitored as described above.
INCLUSION CRITERIA:
PROCUREMENT:
Referred patients will initially be consented for procurement of blood for generation of
the transduced ATL. Eligibility criteria at this stage include:
- Diagnosis of recurrent CD30+ HL or CD30+ NHL, or newly diagnosed patients unable to
receive or complete standard therapy OR diagnosis of relapsed/refractory CD30+ HL or
CD30+ NHL with a treatment plan that will include high dose therapy and stem cell
transplantation
- CD30 positive tumor (result can be pending at this time)
- Hgb > 8.0
- Informed consent explained to, understood by and signed by patient/guardian.
Patient/guardian given copy of informed consent.
- Karnofsky or Lansky score greater than 60%
TREATMENT:
Diagnosis - CD30+ HL or CD30+ NHL:
1. During the Dose Escalation Phase: only adult patients with active disease failing
standard therapy
2. After Dose Escalation: any patient (children or adults) newly diagnosed, unable to
receive or complete standard therapy OR diagnosis of relapsed/refractory CD30+ HL or
CD30+ NHL with a treatment plan that will include high dose therapy and autologous
stem cell transplantation. (During dose escalation: only adult patients (age 18 and
older; After Dose Escalation: any patient (children ages 0-17 or adults)
- CD30 positive tumor
- Bilirubin 1.5 times or less than upper limit of normal.
- AST 3 times or less than upper limit of normal.
- Serum creatinine 1.5 times or less than upper limit of normal.
- Pulse oximetry of > 90% on room air
- Karnofsky or Lansky score of > 60%.
- Available autologous T cells with 15% or more expression of CD30CAR determined by
flow-cytometry.
- Recovered from acute toxic effects of all prior chemotherapy at least one week
and 30 days from prior chemotherapy before entering this study
- Adequate pulmonary function with FEV1, FVC and DLCO greater than or equal to 50%
of expected corrected for hemoglobin.
- Sexually active patients must be willing to utilize one of the more effective
birth control methods during the study and for 6 months after the study is
concluded. The male partner should use a condom.
- Patients or legal guardians must sign an informed consent indicating that they
are aware this is a research study and have been told of its possible benefits
and toxic side effects. Patients or their guardians will be given a copy of the
consent form.
EXCLUSION CRITERIA:
PROCUREMENT:
- Active infection with HIV, HTLV, HBV, HCV (can be pending at this time).
TREATMENT:
- Currently receiving any investigational agents or received any tumor vaccines within
the previous six weeks.
- Received anti-CD30 antibody-based therapy within the previous 4 weeks.
- History of hypersensitivity reactions to murine protein-containing products.
- Pregnant or lactating.
- Tumor in a location where enlargement could cause airway obstruction.
- Current use of systemic corticosteroids.
We found this trial at
3
sites
University of North Carolina at Chapel Hill Carolina’s vibrant people and programs attest to the...
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Houston Methodist Hospital Houston Methodist is comprised of a leading academic medical center in the...
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Texas Children's Hospital Texas Children's Hospital, located in Houston, Texas, is a not-for-profit organization whose...
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