To prepare the DIPG/HGG specific T cells (GD2-C7R T cells), research staff will take some
blood from the patient. We will grow the GD2.C7R T cells by infecting the T cells with a
retroviral vector (a special virus that can carry a new gene into cells) containing one gene
that can recognize and kill DIPG/HGG cells (GD2.CAR) and the new gene called C7R that will
help these cells survive longer. After the new genes have been put into the T cells, the
cells will be tested to make sure that they kill GD2-positive DIPG/HGG cells.
Because we are growing the cells in the laboratory, we will also need to take blood to test
for infectious viruses such as hepatitis and HIV (the virus that causes AIDS), and we will
also ask patients to complete a questionnaire that is given to blood donors.
The cells generated will be frozen and stored to give back to the patient. Because patients
will have received cells with a new gene in them patients will be followed for a total of 15
years to see if there are any long term side effects of gene transfer.
Patients will be assigned a dose of GD2-C7R T cells. There is one dose where patients will
only receive GD2 T cells without the C7R. The assigned dose of cells is adjusted based on
body weight and height.
In this study, patients will receive the GD2-(C7R) cells and also receive cyclophosphamide
and fludarabine. These two drugs are standard chemotherapy medicines and may be given before
the T cells to make space in the blood for the T cells to grow after receiving them.
Cyclophosphamide and fludarabine will be given intravenously (through an i.v. needle inserted
in a vein or your central line) for 2 days and then fludarabine alone on the third day.
The patient will be given an injection of GD2-(C7R) T cells into the vein through an IV line
at the assigned dose. Before receiving the T cell infusion, the patient may be given a dose
of Benadryl (diphenhydramine) and Tylenol (acetaminophen). The infusion will take between 1
and 10 minutes. We will then monitor the patient in the hospital for at least 3 days. The
treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital.
The patient will need to stay in Houston for up to 4 weeks after the infusion so we can
monitor for side effects.
The patient will have follow-up visits at weeks 1, 2, 3, 4, 6, and 8, then at months 3, 6, 9,
and 12, and then twice a year for the next 4 years and annually for the next 10 years for a
total of 15 years. The patient will also have scheduled disease evaluations after the T-cell
injection at week 6 and then as clinically needed.
After disease re-evaluation, the patient may be eligible to receive one additional dose of T
cells if the following criteria are met: (1) The disease has not gotten worse and/or it seems
the patient may benefit in the future from an additional dose. (2) The patient has not had a
severe side effect caused by the infusion of GD2-C7R T cells. The dose will be at the same
dose level as the first infusion and separated by at least 3 months such that we can make
sure there are no severe side effects between infusions. If the patient receives an
additional dose of GD2-(C7R) T-cells, then they will need to stay in Houston for up to 4
weeks after the infusion as well so we can monitor for side effects.
Medical tests before treatment--
Before being treated, the patient will receive a series of standard medical tests:
- Physical exam
- Blood tests to measure blood cells, kidney and liver function
- Measurements of the tumor by routine MRI (Magnetic Resonance Imaging)
Medical tests during and after treatment--
The patient will receive standard medical tests when they are getting the infusions and
afterwards:
- Physical exams
- Blood tests to measure blood cells, kidney and liver function
- Measurements of the tumor by MRI imaging studies and spinal fluid analysis 6 weeks after
the infusion and repeat MRI imaging at 3 months.
Spinal Fluid Tests: One spinal tap will be performed as part of the study. This procedure is
usually done under general anesthesia in children. After the skin is numbed, a long needle is
placed into the lower back to remove 1-2 ml of spinal fluid (less than half a teaspoon).
To learn more about the way the GD2-(C7R) T cells are working and how long they last in the
body, an extra amount of blood will be obtained on the day that chemotherapy starts, the day
of the T-cell infusion(s) and at the end of the T-cell infusion(s), 1, 2, 4, 6 and 8 weeks
after the T-cell infusion(s) and every 3 months for the 1st year, every 6 months for the next
4 years and annually for the next 10 years. The amount of blood taken will be based on weight
with up to a maximum of 60 mL (12 teaspoons) of blood to be obtained at any one time. For
children, the total amount of blood drawn will not be more than 3 mL (less than 1 teaspoon)
per 1 kg of body weight on any one day. This volume is considered safe, but may be decreased
if the patient is anemic (has a low red blood cell count).
During the time points listed above, if the GD2-(C7R) T cells are found in the patient's
blood at a certain amount, an extra 5 mL (about 1 teaspoon) of blood may need to be collected
for additional testing.
If the patient has a procedure where tumor samples are obtained, like a spinal tap evaluation
or tumor biopsy, we will request a sample to be used for research purposes.
The patient will receive supportive care for any acute or chronic toxicities, including blood
components or antibiotics, and other intervention as appropriate.
Procurement Inclusion Criteria:
1. Patients with histologically confirmed, GD2-expressing newly diagnosed DIPG or HGG or
confirmation of positive H3K27M mutation status if sufficient tissue for GD2 staining
by IHC is not available.
2. Tumors less than 5 cm in maximum dimension at enrollment
1. Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks
post-radiotherapy remain eligible for study
2. Tumors with >25% increase in size on post-radiation imaging may be reassessed
with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently ≤
25% increased compared with time of diagnosis
3. Measurable disease on at least 2 dimensions on MRI
4. Age 12 months to 18 years
5. Functional score (Karnofsky/Lansky) ≥ 50 expected at infusion
6. Organ function:
1. ANC > 1000 cells/ul
2. Platelet count > 100,000 cells/ul
3. Total bilirubin < 1.5x ULN
4. ALT and AST < 5x ULN
5. Serum creatinine or kidney within 2x ULN for age
Procurement Exclusion Criteria:
1. Patients who are pregnant or breast feeding
2. Any patient with other risk factors for whom administration of investigational agent
is deemed not in the patient's best interest, in the opinion of the investigator.
Treatment Inclusion Criteria
1. Patients with histologically confirmed, GD2-expressing newly diagnosed DIPG or HGG or
confirmation of positive H3K27M mutation status if sufficient tissue for GD2 staining
by IHC is not available.
2. Tumors less than 5 cm in maximum dimension at enrollment
1. Tumors with ≤25% increase in size (on any dimension) on MRI 4-8 weeks
post-radiotherapy remain eligible for study
2. Tumors with >25% increase in size on post-radiation imaging may be reassessed
with repeat MRI in 4-6 weeks, and are eligible if tumor size is subsequently ≤
25% increased compared with time of diagnosis
3. Measurable disease on at least 2 dimensions on MRI
4. Central line (PICC or other) in place or planned to be placed
5. Age 12 months to 18 years
6. Functional score (Karnofsky/Lansky) ≥ 50
7. Patients must have completed radiation therapy. Radiation therapy must be completed at
least 4 weeks prior to administration of investigational agent
8. Stable neurologic exam for 7 days prior to enrollment
9. Stable or decreasing dose of steroids (max. allowable dose of dexamethasone is 0.1
mg/kg/day over the past 7 days prior to infusion of investigational therapy)
10. Organ function:
1. ANC > 1000 cells/ul
2. Platelet count > 100,000 cells/ul
3. Total bilirubin < 1.5x ULN
4. ALT and AST < 5x ULN
5. Serum creatinine or kidney within 2x ULN for age
Treatment Exclusion Criteria
1. Patients who received any other forms of immunotherapy ≤ 42 days before administration
of investigational agent
2. Patients who received colony-stimulating factors within 14 days prior to
administration of lymphodepletion
3. Patients receiving any concurrent anti-cancer therapy
4. Patients who are pregnant or breast feeding
5. Any patient with other risk factors for whom administration of investigational agent
is deemed not in the patient's best interest, in the opinion of the investigator.
