Ignite Creation Date:
2024-05-06 @ 9:50 AM
Last Modification Date:
2024-10-26 @ 12:20 PM
Study NCT ID:
NCT03081910
Status:
RECRUITING
Last Update Posted:
2024-02-12
First Post:
2017-03-08
Brief Title:
Autologous T-Cells Expressing a Second Generation CAR for Treatment of T-Cell Malignancies Expressing CD5 Antigen
Sponsor:
Baylor College of Medicine
Organization:
Baylor College of Medicine
Study Overview
Official Title:
Phase 1 Therapy With Manufactured Autologous T-Cells Expressing a Second Generation Chimeric Antigen Receptor CAR for Treatment of T-Cell Malignancies Expressing CD5 Antigen
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MAGENTA
Brief Summary:
Patients eligible for this study have a type of blood cancer called T-cell leukemia or lymphoma lymph gland cancer
The body has different ways of fighting infection and disease No one way seems perfect for fighting cancers This research combines two different ways of fighting disease antibodies and T cells Antibodies are proteins that protect the body from bacterial and other diseases T cells or T lymphocytes are special infection-fighting blood cells that can kill other cells including tumor cells Both antibodies and T cells have shown promise treating patients with cancers but have not been strong enough to cure most patients
T lymphocytes can kill tumor cells but there normally are not enough of them Some researchers have taken T cells from a persons blood grown more in the lab then given them back to the person In some patients whove had recent bone marrow or stem cell transplant the number of T cells in their blood may not be enough to grow in the lab In this case T cells may be collected from their previous transplant donor who has a similar tissue type
The antibody used in this study called anti-CD5 first came from mice that have developed immunity to human leukemia This antibody sticks to T-cell leukemia or lymphoma cells because of a substance on the outside of these cells called CD5 CD5 antibodies have been used to treat people with T-cell leukemia and lymphoma For this study anti-CD5 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 In the lab investigators have also found that T cells work better if stimulating proteins such as one called CD28 are also added Adding the CD28 makes the cells grow better and last longer in the body giving them a better chance of killing the leukemia or lymphoma cells
In this study investigators will attach the CD5 chimeric receptor with CD28 added to it to the patients T cells or the previous bone marrow transplant donors T cells The investigators will then test how long the cells last The decision to use the bone marrow transplant donors T cells instead of the patients will be based on 1 whether there is an available and willing donor and 2 the likelihood of the patients T cells being able to grow in the lab These CD5 chimeric receptor T cells with CD28 are investigational products not approved by the FDA
The body has different ways of fighting infection and disease No one way seems perfect for fighting cancers This research combines two different ways of fighting disease antibodies and T cells Antibodies are proteins that protect the body from bacterial and other diseases T cells or T lymphocytes are special infection-fighting blood cells that can kill other cells including tumor cells Both antibodies and T cells have shown promise treating patients with cancers but have not been strong enough to cure most patients
T lymphocytes can kill tumor cells but there normally are not enough of them Some researchers have taken T cells from a persons blood grown more in the lab then given them back to the person In some patients whove had recent bone marrow or stem cell transplant the number of T cells in their blood may not be enough to grow in the lab In this case T cells may be collected from their previous transplant donor who has a similar tissue type
The antibody used in this study called anti-CD5 first came from mice that have developed immunity to human leukemia This antibody sticks to T-cell leukemia or lymphoma cells because of a substance on the outside of these cells called CD5 CD5 antibodies have been used to treat people with T-cell leukemia and lymphoma For this study anti-CD5 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 In the lab investigators have also found that T cells work better if stimulating proteins such as one called CD28 are also added Adding the CD28 makes the cells grow better and last longer in the body giving them a better chance of killing the leukemia or lymphoma cells
In this study investigators will attach the CD5 chimeric receptor with CD28 added to it to the patients T cells or the previous bone marrow transplant donors T cells The investigators will then test how long the cells last The decision to use the bone marrow transplant donors T cells instead of the patients will be based on 1 whether there is an available and willing donor and 2 the likelihood of the patients T cells being able to grow in the lab These CD5 chimeric receptor T cells with CD28 are investigational products not approved by the FDA
Detailed Description:
To make the T cells the investigators will take blood from the patient or from the previous bone marrow transplant donor and stimulate it with growth factors to make the T cells grow To get the CD5 antibody and CD28 to attach to the surface of the T cell investigators insert the antibody gene into the T cell This is done with a virus called a retrovirus that has been made for this study and will carry the antibody gene into the T cell This virus also helps investigators find the T cells in the patients blood after they are injected Because the patient will have received cells with a new gene in them the patient will be followed for a total of 15 years to see if there are any long term side effects of gene transfer
When the patient is enrolled on this study they will be assigned a dose of CD5 chimeric receptor-T cells Several studies suggest that the infused T cells need room to be able to proliferate grow and accomplish their functions and that this may not happen if there are too many other T cells in circulation Because of that the patient will receive two chemotherapy medications prior to receiving the CD5 chimeric receptor-T cells
One medication is called cyclophosphamide and the other fludarabine The patient will receive 3 daily doses of each drug ending at least one day before the patient receives the chimeric receptor-T cells These drugs will decrease the numbers of the patients own T cells before the CD5 chimeric receptor T cells are infused and also will help decrease the number of other cells that may interfere with the chimeric receptor-T cells working well These drugs are part of many regimens that are used to treat leukemia or lymphoma and not expected to have any effect on the patients tumor with the doses given
A potential side effect of receiving the chemotherapy as well as receiving CD5CD28 Chimeric Receptor T cells is that it can cause development an Epstein Barr Virus EBV infection which can cause illness or formation of a growth or tumor This side effect can be life threatening or fatal To decrease this risk following the chemotherapy but before administration of the CD5CD28 Chimeric Receptor T cells a dose of Rituximab or a similar drug will be given Rituximab is an IV medication that is approved by the Food and Drug Administration to treat elevated levels of EBV in the body
The patient will be given an injection of CD5CD28 Chimeric Receptor T cells into the vein through an IV at the assigned dose The injection will take from 1 to 10 minutes Before the patient receives the injection they may be given a dose of Benadryl and Tylenol The treatment will be given by the Center for Cell and Gene Therapy at Texas Childrens Hospital or Houston Methodist Hospital
The patient will be followed in the clinic after the injection for up to 3 hours and the patient will have to remain locally for a minimum of 6 weeks after the infusion If there is evidence of EBV reactivation the patient must remain locally for 8 weeks During this initial phase patients will come to the clinic at least twice a week Patients will be monitored closely for any side effects including signs of viral infection or overgrowth of virus-infected cells that can behave like a tumor and require specific treatment These side effects may require hospitalization for evaluation and management
If after a 4-6 week evaluation period after the infusion the patient has achieved a complete response measured by bone marrow or radiology scans the patients primary oncology doctors may decide the patient should proceed to bone marrow transplant at which time the patient will be removed from the treatment portion of the study
Before being treated the patient will receive a series of standard medical tests
Physical exam and History Blood tests to measure blood cells kidney and liver function Pregnancy test for female patients who are of child bearing potential Measurements of the patients tumor by scans andor bone marrow studies
The patient will also receive standard medical tests during treatment and after
Physical exams and History Blood tests to measure blood cells kidney and liver function Blood tests to check for any evidence of viral infection
Graft versus Host Disease assessments
Measurements of the patients tumor by scans andor bone marrow studies 6-8 weeks after the infusion and then per standard of care
To learn more about the way the CD5 chimeric receptor-T cells are working and how long they last in the body extra blood will be drawn The total amount on any day is about 10 teaspoons 50 mL or no more than 3 mL per 22 pounds body weight in children This volume is considered safe but may be decreased if the patient is anemic This blood may be drawn from a central line if the patient has one Blood will be taken before the chemotherapy drugs several hours after the T cell infusion at 1 week 2 weeks 3 weeks optional 4 weeks 6 weeks and 8 weeks optional after the infusion at 3 months 6 months 9 months at 1 year every 6 months for 4 years then yearly for a total of 15 years We will also test blood to check for signs of viral infection at the following time points within 1 to 2 weeks prior to chemotherapy drugs prior to T cell infusion then at weeks 1 2 3 4 6 8 for all patients and months 3 6 9 12 for patients who do not proceed to bone marrow transplant The total blood drawn during participation in this study will not exceed 280 teaspoons
Once the dose escalation portion of the study is completed the trial will be expanded and treat up to an additional 6 patients 2 cohorts at the MTD in each group to gather additional safety data and preliminary efficacy data
When the patient is enrolled on this study they will be assigned a dose of CD5 chimeric receptor-T cells Several studies suggest that the infused T cells need room to be able to proliferate grow and accomplish their functions and that this may not happen if there are too many other T cells in circulation Because of that the patient will receive two chemotherapy medications prior to receiving the CD5 chimeric receptor-T cells
One medication is called cyclophosphamide and the other fludarabine The patient will receive 3 daily doses of each drug ending at least one day before the patient receives the chimeric receptor-T cells These drugs will decrease the numbers of the patients own T cells before the CD5 chimeric receptor T cells are infused and also will help decrease the number of other cells that may interfere with the chimeric receptor-T cells working well These drugs are part of many regimens that are used to treat leukemia or lymphoma and not expected to have any effect on the patients tumor with the doses given
A potential side effect of receiving the chemotherapy as well as receiving CD5CD28 Chimeric Receptor T cells is that it can cause development an Epstein Barr Virus EBV infection which can cause illness or formation of a growth or tumor This side effect can be life threatening or fatal To decrease this risk following the chemotherapy but before administration of the CD5CD28 Chimeric Receptor T cells a dose of Rituximab or a similar drug will be given Rituximab is an IV medication that is approved by the Food and Drug Administration to treat elevated levels of EBV in the body
The patient will be given an injection of CD5CD28 Chimeric Receptor T cells into the vein through an IV at the assigned dose The injection will take from 1 to 10 minutes Before the patient receives the injection they may be given a dose of Benadryl and Tylenol The treatment will be given by the Center for Cell and Gene Therapy at Texas Childrens Hospital or Houston Methodist Hospital
The patient will be followed in the clinic after the injection for up to 3 hours and the patient will have to remain locally for a minimum of 6 weeks after the infusion If there is evidence of EBV reactivation the patient must remain locally for 8 weeks During this initial phase patients will come to the clinic at least twice a week Patients will be monitored closely for any side effects including signs of viral infection or overgrowth of virus-infected cells that can behave like a tumor and require specific treatment These side effects may require hospitalization for evaluation and management
If after a 4-6 week evaluation period after the infusion the patient has achieved a complete response measured by bone marrow or radiology scans the patients primary oncology doctors may decide the patient should proceed to bone marrow transplant at which time the patient will be removed from the treatment portion of the study
Before being treated the patient will receive a series of standard medical tests
Physical exam and History Blood tests to measure blood cells kidney and liver function Pregnancy test for female patients who are of child bearing potential Measurements of the patients tumor by scans andor bone marrow studies
The patient will also receive standard medical tests during treatment and after
Physical exams and History Blood tests to measure blood cells kidney and liver function Blood tests to check for any evidence of viral infection
Graft versus Host Disease assessments
Measurements of the patients tumor by scans andor bone marrow studies 6-8 weeks after the infusion and then per standard of care
To learn more about the way the CD5 chimeric receptor-T cells are working and how long they last in the body extra blood will be drawn The total amount on any day is about 10 teaspoons 50 mL or no more than 3 mL per 22 pounds body weight in children This volume is considered safe but may be decreased if the patient is anemic This blood may be drawn from a central line if the patient has one Blood will be taken before the chemotherapy drugs several hours after the T cell infusion at 1 week 2 weeks 3 weeks optional 4 weeks 6 weeks and 8 weeks optional after the infusion at 3 months 6 months 9 months at 1 year every 6 months for 4 years then yearly for a total of 15 years We will also test blood to check for signs of viral infection at the following time points within 1 to 2 weeks prior to chemotherapy drugs prior to T cell infusion then at weeks 1 2 3 4 6 8 for all patients and months 3 6 9 12 for patients who do not proceed to bone marrow transplant The total blood drawn during participation in this study will not exceed 280 teaspoons
Once the dose escalation portion of the study is completed the trial will be expanded and treat up to an additional 6 patients 2 cohorts at the MTD in each group to gather additional safety data and preliminary efficacy data
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None