Fucosylated T Cells for Graft Versus Host Disease (GVHD) Prevention
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Blood Cancer, Lymphoma, Hematology, Leukemia |
| Therapuetic Areas: | Hematology, Oncology |
| Healthy: | No |
| Age Range: | Any - 80 |
| Updated: | 1/17/2019 |
| Start Date: | July 30, 2015 |
| End Date: | July 2019 |
Pilot Study of Infusion of Fucosylated Regulatory T Cells to Prevent Graft Versus Host Disease
Any time the words "you," "your," "I," or "me" appear, it is meant to apply to the potential
participant.
T-cells are white blood cells that are important to the immune system. The T cells for this
study (called regulatory T-cells, or Tregs) will be from a donor who is not related to you.
Before the Tregs are given to you, they may be changed in the laboratory to make use of sugar
that is found in small amounts in blood cells through a process called fucosylation. They are
then called fucosylated Tregs. Adding more sugars to the Tregs in the laboratory is designed
to help the Tregs find their way faster to the bone marrow, which may help low blood counts
to recover faster.
The goal of this clinical research study is to learn if it is safe and practical to give
fucosylated Tregs to patients who will receive a matched related donor (MRD), a matched
unrelated donor (MUD), or cord blood transplant. Researchers also want to learn if these
Tregs may prevent or reduce the effects of graft-versus host disease (GVHD). GVHD can result
from a reaction of the transplanted cord blood cells against certain tissues in the body.
This is an investigational study. Fucosylation of Tregs is not an FDA-approved process. It is
currently being used for research purposes only. Fludarabine, melphalan, cyclophosphamide and
rituximab are FDA approved and commercially available to be given to patients with leukemia
or lymphoma having a cord blood transplant. Total body irradiation is delivered using
FDA-approved and commercially available methods.
Up to 47 patients will take part in this study. All will be enrolled at MD Anderson.
participant.
T-cells are white blood cells that are important to the immune system. The T cells for this
study (called regulatory T-cells, or Tregs) will be from a donor who is not related to you.
Before the Tregs are given to you, they may be changed in the laboratory to make use of sugar
that is found in small amounts in blood cells through a process called fucosylation. They are
then called fucosylated Tregs. Adding more sugars to the Tregs in the laboratory is designed
to help the Tregs find their way faster to the bone marrow, which may help low blood counts
to recover faster.
The goal of this clinical research study is to learn if it is safe and practical to give
fucosylated Tregs to patients who will receive a matched related donor (MRD), a matched
unrelated donor (MUD), or cord blood transplant. Researchers also want to learn if these
Tregs may prevent or reduce the effects of graft-versus host disease (GVHD). GVHD can result
from a reaction of the transplanted cord blood cells against certain tissues in the body.
This is an investigational study. Fucosylation of Tregs is not an FDA-approved process. It is
currently being used for research purposes only. Fludarabine, melphalan, cyclophosphamide and
rituximab are FDA approved and commercially available to be given to patients with leukemia
or lymphoma having a cord blood transplant. Total body irradiation is delivered using
FDA-approved and commercially available methods.
Up to 47 patients will take part in this study. All will be enrolled at MD Anderson.
Central Venous Catheter Placement:
You will first have a central venous catheter (CVC) placed. A CVC is a sterile flexible tube
that will be placed into a large vein while you are under local anesthesia. Your doctor will
explain this procedure to you in more detail, and you will be required to sign a separate
consent form for it.
The chemotherapy, some of the other drugs in this study, the Tregs, and the MRD, MUD or cord
blood transplant will be given by vein through your CVC. Some blood samples will also be
drawn through your CVC. The CVC will remain in your body for about 2-5 months.
Study Treatments:
If you are found to be eligible to take part in this study, you will be assigned to a dose
level of Tregs based on when you joined this study. You may receive fucosylated or
non-fucosylated Treg cells. Two dose levels of fucosylated Tregs will be tested. Up to 3
participants will be enrolled in Dose Level 1, and up to 17 will be in Dose Level 2. The
first group of participants will receive the lower dose level. The next group will receive a
higher dose than the first group, if no intolerable side effects were seen.
The next 10 participants will receive non-fucosylated Tregs at Dose Level 2.
The last 34 patients enrolled in the study will be will be randomly assigned (as in the flip
of a coin) to 1 of 2 study groups and will have an equal chance of receiving either
fucosylated or non-fucosylated Treg cells.
You will receive 1 of 2 preparative regimens before your transplant. These regimens are used
to prepare your body to receive the transplant. Your study doctor will decide which regimen
is best for you.
Regimen #1:
On Day -12, you will receive rituximab by vein over 4-6 hours, if you are receiving it. This
will depend on the disease that you have.
On Day -9, you will be admitted to the hospital and given fluids by vein to hydrate you.
On Day -8, you will receive fludarabine and cyclophosphamide by vein over 1 hour. You will
also receive mesna by vein over 30-60 minutes before the cyclophosphamide dose and then every
4 hours for a total of 5 doses. Mesna is given to lower the risk of side effects to the
bladder caused by cyclophosphamide.
On Days -7, -6, and -5, you will receive fludarabine by vein over 1 hour.
On Day -4, you will receive a single treatment of low-dose total body irradiation as part of
the standard of care for stem cell transplants. You will receive a separate consent form that
describes this procedure and its risks.
On Day -1, you will receive the Tregs by vein over 30-60 minutes.
On Day 0, you will receive your stem cell transplant through the CVC over about 30 minutes to
several hours depending on the donor type of stem cell transplant you receive.
Regimen #2:
On Day -12, you will receive rituximab by vein over 4-6 hours, if you are receiving it. This
will depend on the disease that you have.
On Day -6, you will be admitted to the hospital and given fluids by vein to hydrate you.
On Days -5, -4, -3 and -2, you will receive fludarabine by vein over 1 hour.
On Day -2, you will receive melphalan by vein over 30 mins.
On Day -1, you will receive the Tregs by vein over 30-60 minutes.
On Day 0, you will receive your stem cell transplant through the CVC over about 30 minutes to
several hours depending on the donor type of stem cell transplant you receive.
Supportive Drugs:
You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff about how the drugs are given and their risks.
Starting on Day -3, you will receive sirolimus by mouth once a day. You will receive
mycophenolate mofetil (MMF) as a tablet by mouth 3 times a day.
If you are not able to take the MMF tablet by mouth, you will receive MMF by vein over 2
hours. If you do not have GVHD at Day 100, the dose of MMF will be gradually lowered. If you
have GVHD, MMF may be stopped 7 days after the GVHD is controlled. If you do not have GVHD at
Day 180 after your transplant, the dose of sirolimus will be gradually lowered. Your doctor
will discuss this with you.
You will receive filgrastim as an injection under the skin 1 time a day, starting on Day 0
for cord blood transplant or Day 7 for a matched related or MUD transplant, until your blood
cell levels return to normal. Filgrastim is designed to help with the growth of white blood
cells.
Study Visits:
As part of standard care, you will remain in the hospital for about 4 weeks after the
transplant. After you are released from the hospital, you will continue as an outpatient in
the Houston area to be monitored for infections and transplant-related complications.
On Days -10, -1, 0, +1, +3, +7, +14, +21, and then at 1, 2, 3, 6, and 12 months after the
transplant, blood (about 3 tablespoons) will be drawn to check your immune function, response
to the T cells, inflammatory responses, and for GVHD markers. If possible, the blood will be
collected during standard of care blood draws so that no additional needle sticks will be
needed.
About 1, 3, 6, and 12 months after the transplant:
- You will have a physical exam.
- You will be checked for possible reactions to the transplant and study drugs, including
GVHD.
- Blood (about 4 teaspoons) will be drawn for routine tests, to check for cytomegalovirus
(CMV), and for genetic tests to learn if your body has accepted the donor cells.
Urine will be collected for routine tests.
- If the doctor thinks it is needed, you will have a bone marrow aspiration to check the
status of the disease. To collect a bone marrow aspiration/biopsy, an area of the hip or
other site is numbed with anesthetic, and a small amount of bone marrow and bone is
withdrawn through a large needle.
- If you have lymphoma or Hodgkin's Disease and the doctor thinks it is needed, you will
have a CT scan of your neck, chest, abdomen, and pelvis to check the status of the
disease.
Length of Study:
You will be on study for up to 1 year. You will be taken off study early if the disease gets
worse, if intolerable side effects occur, if not enough T cells can be created, if you are
unable to follow study directions, or if your doctor thinks it is in your best interest.
You will first have a central venous catheter (CVC) placed. A CVC is a sterile flexible tube
that will be placed into a large vein while you are under local anesthesia. Your doctor will
explain this procedure to you in more detail, and you will be required to sign a separate
consent form for it.
The chemotherapy, some of the other drugs in this study, the Tregs, and the MRD, MUD or cord
blood transplant will be given by vein through your CVC. Some blood samples will also be
drawn through your CVC. The CVC will remain in your body for about 2-5 months.
Study Treatments:
If you are found to be eligible to take part in this study, you will be assigned to a dose
level of Tregs based on when you joined this study. You may receive fucosylated or
non-fucosylated Treg cells. Two dose levels of fucosylated Tregs will be tested. Up to 3
participants will be enrolled in Dose Level 1, and up to 17 will be in Dose Level 2. The
first group of participants will receive the lower dose level. The next group will receive a
higher dose than the first group, if no intolerable side effects were seen.
The next 10 participants will receive non-fucosylated Tregs at Dose Level 2.
The last 34 patients enrolled in the study will be will be randomly assigned (as in the flip
of a coin) to 1 of 2 study groups and will have an equal chance of receiving either
fucosylated or non-fucosylated Treg cells.
You will receive 1 of 2 preparative regimens before your transplant. These regimens are used
to prepare your body to receive the transplant. Your study doctor will decide which regimen
is best for you.
Regimen #1:
On Day -12, you will receive rituximab by vein over 4-6 hours, if you are receiving it. This
will depend on the disease that you have.
On Day -9, you will be admitted to the hospital and given fluids by vein to hydrate you.
On Day -8, you will receive fludarabine and cyclophosphamide by vein over 1 hour. You will
also receive mesna by vein over 30-60 minutes before the cyclophosphamide dose and then every
4 hours for a total of 5 doses. Mesna is given to lower the risk of side effects to the
bladder caused by cyclophosphamide.
On Days -7, -6, and -5, you will receive fludarabine by vein over 1 hour.
On Day -4, you will receive a single treatment of low-dose total body irradiation as part of
the standard of care for stem cell transplants. You will receive a separate consent form that
describes this procedure and its risks.
On Day -1, you will receive the Tregs by vein over 30-60 minutes.
On Day 0, you will receive your stem cell transplant through the CVC over about 30 minutes to
several hours depending on the donor type of stem cell transplant you receive.
Regimen #2:
On Day -12, you will receive rituximab by vein over 4-6 hours, if you are receiving it. This
will depend on the disease that you have.
On Day -6, you will be admitted to the hospital and given fluids by vein to hydrate you.
On Days -5, -4, -3 and -2, you will receive fludarabine by vein over 1 hour.
On Day -2, you will receive melphalan by vein over 30 mins.
On Day -1, you will receive the Tregs by vein over 30-60 minutes.
On Day 0, you will receive your stem cell transplant through the CVC over about 30 minutes to
several hours depending on the donor type of stem cell transplant you receive.
Supportive Drugs:
You will be given standard drugs to help decrease the risk of side effects. You may ask the
study staff about how the drugs are given and their risks.
Starting on Day -3, you will receive sirolimus by mouth once a day. You will receive
mycophenolate mofetil (MMF) as a tablet by mouth 3 times a day.
If you are not able to take the MMF tablet by mouth, you will receive MMF by vein over 2
hours. If you do not have GVHD at Day 100, the dose of MMF will be gradually lowered. If you
have GVHD, MMF may be stopped 7 days after the GVHD is controlled. If you do not have GVHD at
Day 180 after your transplant, the dose of sirolimus will be gradually lowered. Your doctor
will discuss this with you.
You will receive filgrastim as an injection under the skin 1 time a day, starting on Day 0
for cord blood transplant or Day 7 for a matched related or MUD transplant, until your blood
cell levels return to normal. Filgrastim is designed to help with the growth of white blood
cells.
Study Visits:
As part of standard care, you will remain in the hospital for about 4 weeks after the
transplant. After you are released from the hospital, you will continue as an outpatient in
the Houston area to be monitored for infections and transplant-related complications.
On Days -10, -1, 0, +1, +3, +7, +14, +21, and then at 1, 2, 3, 6, and 12 months after the
transplant, blood (about 3 tablespoons) will be drawn to check your immune function, response
to the T cells, inflammatory responses, and for GVHD markers. If possible, the blood will be
collected during standard of care blood draws so that no additional needle sticks will be
needed.
About 1, 3, 6, and 12 months after the transplant:
- You will have a physical exam.
- You will be checked for possible reactions to the transplant and study drugs, including
GVHD.
- Blood (about 4 teaspoons) will be drawn for routine tests, to check for cytomegalovirus
(CMV), and for genetic tests to learn if your body has accepted the donor cells.
Urine will be collected for routine tests.
- If the doctor thinks it is needed, you will have a bone marrow aspiration to check the
status of the disease. To collect a bone marrow aspiration/biopsy, an area of the hip or
other site is numbed with anesthetic, and a small amount of bone marrow and bone is
withdrawn through a large needle.
- If you have lymphoma or Hodgkin's Disease and the doctor thinks it is needed, you will
have a CT scan of your neck, chest, abdomen, and pelvis to check the status of the
disease.
Length of Study:
You will be on study for up to 1 year. You will be taken off study early if the disease gets
worse, if intolerable side effects occur, if not enough T cells can be created, if you are
unable to follow study directions, or if your doctor thinks it is in your best interest.
Inclusion Criteria:
1. Patients with high risk hematologic malignancies, including those with induction
failure and in relapse.
2. Patients must have matched related or matched unrelated donor source OR CB unit(s)
available for the primary transplant which is/are matched with the patient at 4, 5, or
6/6 HLA class I (serological) and II (molecular) antigens. The cord(s) must contain at
least 3 x 107 total nucleated cells/Kg recipient body weight (pre-thaw).
3. Age Criteria: Age >/= 16 and be determined in conjunction with an MDACC pediatrician.
4. Bilirubin
5. Calculated creatinine clearance of >50 mL/min using the Cockcroft-Gault equation for
adult patients 18 to 70 years old based on ideal body weight, and the Schwartz
equation for pediatric patients 6 months to 17 years old.
6. Diffusing capacity for carbon monoxide (DLCO) >/= 45% predicted corrected for
hemoglobin. For children function test, an O2 saturation of >/= 92% on room air.
7. Left ventricular ejection fraction (LEF) >/= 40%.
8. Zubrod performance status /= 60%.
9. Twenty-one or more days must have elapsed since the patient's last radiation or
chemotherapy administration before beginning treatment for stem cell transplant.
Hydrea, Gleevec and other TKI inhibitors as well as intrathecal therapy are accepted
exceptions.
10. A back-up graft identified, in case of graft failure, from any of the following
sources: an available fraction of autologous marrow; or PBPCs harvested and
cryopreserved; or family member donor; or a third cord blood unit.
11. Able to stop all CYP3A4 inhibitors (voriconazole or posaconazole) at least 7 days
before admission.
12. Patient or patient's legal representative, parent(s) or guardian able to sign informed
consent. Age 7-18 able to provide assent.
Exclusion Criteria:
1. HIV seropositivity.
2. Uncontrolled infection, not responding to appropriate antimicrobial agents after seven
days of therapy. The PI is the final arbiter of eligibility.
3. Positive beta HCG in female of child-bearing potential defined as not post-menopausal
for 12 months or no previous surgical sterilization or lactating females.
We found this trial at
1
site
1515 Holcombe Blvd
Houston, Texas 77030
Houston, Texas 77030
713-792-2121
University of Texas M.D. Anderson Cancer Center The mission of The University of Texas MD...
Click here to add this to my saved trials
