Description:
The subject has a type of lymph gland cancer called Lymphoma.
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. 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. They now want to test whether these
genetically modified T cells given after chemotherapy will be more effective at killing
cancer cells.
The gene that will be put into the 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 (CD30.CAR 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.
Several studies suggest that the infused T cells need room to be able to multiply and grow to
accomplish their functions, and that this may not happen if there are too many other T cells
in circulation. Because of that, doctors may use chemotherapy drugs to decrease the level of
circulating T cells prior to the CD30.CAR T cells infusion. This is called "lymphodepletion".
CD30.CAR T cells have previously been studied in lymphoma patients. What is new for this
study is that lymphodepletion chemotherapy will be administered in patients who are not post
autologous transplant in the hope that it will result in more durable anti-tumor effects.
Title
- Brief Title: CD30 CAR T Cells, Relapsed CD30 Expressing Lymphoma (RELY-30)
- Official Title: Phase I Study of Relapsed CD30 Expressing Lymphoma Treated With CD30 CAR T Cells (RELY-30)
Clinical Trial IDs
- ORG STUDY ID:
H-37966, RELY-30
- SECONDARY ID:
RELY-30
- NCT ID:
NCT02917083
Conditions
- Hodgkin's Lymphoma
- Non-Hodgkin Lymphoma
Interventions
| Drug | Synonyms | Arms |
|---|
| Cyclophosphamide | Cytoxan | CD30.CAR T Cells |
| Fludarabine | Fludara | CD30.CAR T Cells |
Purpose
The subject has a type of lymph gland cancer called Lymphoma.
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. 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. They now want to test whether these
genetically modified T cells given after chemotherapy will be more effective at killing
cancer cells.
The gene that will be put into the 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 (CD30.CAR 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.
Several studies suggest that the infused T cells need room to be able to multiply and grow to
accomplish their functions, and that this may not happen if there are too many other T cells
in circulation. Because of that, doctors may use chemotherapy drugs to decrease the level of
circulating T cells prior to the CD30.CAR T cells infusion. This is called "lymphodepletion".
CD30.CAR T cells have previously been studied in lymphoma patients. What is new for this
study is that lymphodepletion chemotherapy will be administered in patients who are not post
autologous transplant in the hope that it will result in more durable anti-tumor effects.
Detailed Description
To prepare the CD30.CAR T cells, research staff will take some blood from the subject. This
would be drawn as two separate blood collections.
Alternatively, if the subject's blood counts are low, staff may collect the cells needed to
prepare T cells by a pheresis procedure. This procedure will involve placing a needle in both
arms, collecting the cells over 3 to 6 hours during which the subject will be required to lie
relatively still.
After the T cells have been collected, some of them will be activated stimulating them with
antibodies and will then be infected with a retroviral vector (a special virus that can
carries a new gene into cells) containing a new gene called anti-CD30 that will make an
antibody to lymphoma cells. The trained cells are called CD30.CAR T cells. Then, the cells
will be tested to make sure that they kill lymphoma cells that express the CD30 antigen and
not normal cells.
The cells generated will be frozen and stored to give back to the subject.
This is a dose escalation study. This means that at the beginning, patients will be started
on the lowest doses (1 of 3 different levels) of CD30.CAR T Cells. Once that dose schedule
proves safe, the next group of patients will be started at a higher dose. This process will
continue until all 3 dose levels are studied. If the side effects are too severe, the dose
will be lowered or the T cell infusions will be stopped. 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.
Subjects will be given one injection of CD30.CAR T cells. The injection will be on Day 0. The
subject may be given a dose of Benadryl and Tylenol before the injection of T cells to
minimize any possible allergic reaction. The injection will take 1-10 minutes. The subject
will be monitored in the clinic after each injection for up to 3 hours.
At the discretion of the study doctor, if the subject has stable disease (the lymphoma did
not grow) or there is a reduction in the size of the lymphoma on imaging studies at week 8
after the T-cell infusion or on subsequent evaluations, then the subject can receive up to
six additional doses of the T cells at 8 to 12 weeks intervals. After each T cell injection,
the subject will be monitored as described above.
If the subject is not post autologous transplant they will receive treatment with
cyclophosphamide and fludarabine (chemotherapy drugs) before the CD30.CAR T cells. These
drugs will decrease the numbers of the patient's T cells before the CD30.CAR T cells are
infused. Although the investigators do not expect any effect on the tumor with the dose that
the patient will receive, these drugs are part of many regimens that are used to treat
lymphoma or leukemia.
To learn more about the way the CD30.CAR T cells are working and how long they last in the
body, extra blood will be drawn. On the day that the subject receives the cells, blood will
be taken before the cells are given and several hours afterwards. Other blood will be drawn
at 1 week, 2 weeks, 3 weeks (optional), 4 weeks, 6 weeks and 8 weeks, every 3 months for 1
year, every 6 months for 4 years, then yearly for a total of 15 years.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| CD30.CAR T Cells | Experimental | Each patient will receive one infusion of CAR modified T cells.
Unless post autologous transplant, patients will receive Cyclophosphamide and Fludarabine to induce lymphopenia.
Patients post autologous stem cell transplantation will receive T cell infusion starting at least 14 days after the date of transplant, unless there is clear evidence of relapse, then T-cell infusion can occur at any time after transplant. No lymphodepleting chemotherapy will be given to these patients. | - Cyclophosphamide
- Fludarabine
|
Eligibility Criteria
PROCUREMENT Inclusion Criteria:
1. Diagnosis of relapsed/refractory HL or NHL.
2. CD30 positive tumor as assayed in a CLIA certified pathology laboratory (result can be
pending at this time)
3. Hgb ≥ 7.0 (may be a transfused value)
4. Informed consent explained to, understood by and signed by patient/guardian.
Patient/guardian given copy of informed consent.
5. Karnofsky or Lansky score of > 60%
TREATMENT Inclusion Criteria:
1. Diagnosis of relapsed/refractory HL or NHL.
2. CD30-positive tumor as assayed in a CLIA certified pathology laboratory.
3. Age 16 to 75 for the first three patients on a dose level; thereafter, if no DLT,
patients aged 12 to 75 can be treated on that dose level.
4. Bilirubin 1.5 times or less than the upper limit of normal.
5. AST 3 times or less than the upper limit of normal.
6. Estimated GFR > 70 mL/min.
7. Pulse oximetry of > 90% on room air
8. EKG shows no significant arrhythmias
9. Karnofsky or Lansky score of > 60%.
10. Available autologous T cells with greater than or equal to 15% expression of CD30CAR
determined by flow-cytometry.
11. Recovered from all acute non-hematologic toxic effects of all prior chemotherapy.
12. Adequate pulmonary function with FEV1, FVC and DLCO greater than or equal to 50% of
expected corrected for hemoglobin.
13. 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.
14. Informed consent explained to, understood by and signed by patient or guardian.
PROCUREMENT Exclusion Criteria:
1. Active infection with HIV or HTLV (can be pending at this time).
2. Active bacterial, fungal or viral infection.
TREATMENT Exclusion Criteria:
1. Currently receiving any investigational agents or received any tumor vaccines within
the previous six weeks.
2. Received anti-CD30 antibody-based therapy within the previous 4 weeks.
3. Subjects with rapidly progressive disease, defined as kinetic failure to previous
chemotherapy.
4. Bulky disease (defined as a 10 cm mass or mediastinal disease with a transverse
diameter exceeding 33% of the transthoracic diameter).
5. History of hypersensitivity reactions to murine protein-containing products.
6. Pregnant or lactating.
7. Tumor in a location where enlargement could cause airway obstruction.
8. Current use of systemic corticosteroids at a dose equivalent to 0.5 mg/kg/day of
prednisone or higher.
9. Active hemorrhagic cystitis.
10. Active bacterial, viral or fungal infection.
11. Symptomatic cardiac disease (NYHA Class III or IV disease).
| Maximum Eligible Age: | 75 Years |
| Minimum Eligible Age: | 12 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Number of Patients with Dose-Limiting Toxicities (DLT) |
| Time Frame: | 6 weeks |
| Safety Issue: | |
| Description: | Each treated patient will be followed for 6 weeks post the T-cell infusion for the evaluation of DLTs. |
Secondary Outcome Measures
| Measure: | Median Number of T cells transduced with the vector |
| Time Frame: | 15 years |
| Safety Issue: | |
| Description: | The investigators will monitor the persistence of these infused cells by measuring the level of the transgene by both phenotypic and molecular analyses. |
| Measure: | Overall Response Rate |
| Time Frame: | 8 weeks |
| Safety Issue: | |
| Description: | Although response is not the primary endpoint of this trial, investigators will summarize tumor response by calculating overall response rates along with exact 95% binomial confidence intervals. |
| Measure: | Mean Number of T cells transduced with the vector |
| Time Frame: | 15 years |
| Safety Issue: | |
| Description: | The investigators will monitor the persistence of these infused cells by measuring the level of the transgene by both phenotypic and molecular analyses. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Baylor College of Medicine |
Trial Keywords
- chimeric antigen receptors
- immunotherapy
- CAR T-cells
- lymphoma
- Cyclophosphamide
- fludarabine
Last Updated
June 10, 2021
