Ignite Creation Date:
2024-05-06 @ 12:32 AM
Last Modification Date:
2024-10-26 @ 10:51 AM
Study NCT ID:
NCT01604031
Status:
TERMINATED
Last Update Posted:
2016-02-08
First Post:
2012-05-04
Brief Title:
Treatment of B-CLL With Autologous IL2 and CD40 Ligand-Expressing Tumor Cells Lenalidomide
Sponsor:
Baylor College of Medicine
Organization:
Baylor College of Medicine
Study Overview
Official Title:
Treatment of B-CLL With Autologous IL2 and CD40 Ligand-Expressing Tumor Cells Lenalidomide
Status:
TERMINATED
Status Verified Date:
2016-02
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:
TAIL
Brief Summary:
This is a research study to determine the safety and effectiveness of using special cells that may make the subjects immune system fight their chronic lymphocytic leukemia CLL in combination with a drug called Lenalidomide
To do this the investigators will put a special gene into cancer cells that have been taken from the subject This will be done in the laboratory This gene will make the cells produce interleukin 2 IL-2 which is a natural substance that may help the subjects immune system kill cancer cells Additionally the investigators will stimulate the cancer cells with normal embryonic fibroblasts cells that develop into normal connective tissues in the body so that they will make another natural protein called CD40 ligand CD40L Some of these cells will then be put back into the subjects body with the goal that they will act like a vaccine and stimulate the immune system to attack the CLL cells
The investigators have already conducted a study similar to this in other subjects with CLL In those subjects the investigators saw some changes in the subjects immune system that might indicate that the modified cells were helping their immune system fight the cancer However in most of the subjects this change in the immune system went away after the injections were stopped The investigators think that this may be due to a high level of cells called T regulatory cells T regulatory cells are part of the immune system and prevent excessive reactions from other cells in the body Studies have shown that reducing T regulatory cells allows the body to fight the cancer for a longer period of time
Recent studies have shown that using Lenalidomide helps the body reduce T regulatory cells Using Lenalidomide along with the injections shots might help the body fight the cancer for a longer period of time Lenalidomide is also called Revlimid
In this study the investigators want to see if they can make the change in the immune system last longer by giving Lenalidomide before and at the same time as the vaccine The investigators hope that this might produce a better response directed at the CLL cells Subjects will receive injections for about a year
To do this the investigators will put a special gene into cancer cells that have been taken from the subject This will be done in the laboratory This gene will make the cells produce interleukin 2 IL-2 which is a natural substance that may help the subjects immune system kill cancer cells Additionally the investigators will stimulate the cancer cells with normal embryonic fibroblasts cells that develop into normal connective tissues in the body so that they will make another natural protein called CD40 ligand CD40L Some of these cells will then be put back into the subjects body with the goal that they will act like a vaccine and stimulate the immune system to attack the CLL cells
The investigators have already conducted a study similar to this in other subjects with CLL In those subjects the investigators saw some changes in the subjects immune system that might indicate that the modified cells were helping their immune system fight the cancer However in most of the subjects this change in the immune system went away after the injections were stopped The investigators think that this may be due to a high level of cells called T regulatory cells T regulatory cells are part of the immune system and prevent excessive reactions from other cells in the body Studies have shown that reducing T regulatory cells allows the body to fight the cancer for a longer period of time
Recent studies have shown that using Lenalidomide helps the body reduce T regulatory cells Using Lenalidomide along with the injections shots might help the body fight the cancer for a longer period of time Lenalidomide is also called Revlimid
In this study the investigators want to see if they can make the change in the immune system last longer by giving Lenalidomide before and at the same time as the vaccine The investigators hope that this might produce a better response directed at the CLL cells Subjects will receive injections for about a year
Detailed Description:
Previously some of the cancer cells were taken from the subjects body and separated in the laboratory and a specially produced human virus adenovirus that carries the IL-2 gene was put into the cells Adenovirus is a common virus found in human respiratory systems In its normal state it can reproduce and cause a respiratory infection Respiratory illnesses caused by adenovirus infections range from the common cold to pneumonia croup and bronchitis This adenovirus has been changed in the laboratory so that it is not likely to reproduce or cause an infection once it is in the body The gene transfer method used in this study tries to add copies of the IL2 gene that increases the immune response against a tumor
The rest of the cancer cells have been stimulated to express on their surface a substance called the human CD40L These substances IL-2 and CD40L already naturally present in the body are meant to help the immune system fight the cancer
At the point that the doctor feels the subject should begin treatment on this protocol the treatment will be as follows
The subject will begin taking Allopurinol by mouth at 300 mg and will continue taking Allopurinol daily for 14 days Allopurinol is also called Zyloprim and it will be taken to prevent tumor lysis syndrome Tumor lysis syndrome can be a serious condition that occurs sometimes when cancer treatment is started Tumor lysis syndrome can cause other medical problems
Two days after Allopurinol was started the subject will begin taking Lenalidomide The Lenalidomide dose will be 5 mg taken by mouth daily The subject should swallow the capsules whole with water at the same time each day and should not break chew or open the capsules Females of childbearing potential who are caring for the subject should not touch the lenalidomide capsules or bottles without gloves If a dose of lenalidomide is missed it should be taken as soon as possible on the same day If it is missed for the entire day it should not be made up If more than the prescribed dose is taken of lenalidomide and the subject feels poorly she should seek emergency medical care and tell the study staff right away The subject will get 1 cycle of drug per month A max of a 28-day supply of the drug will be provided at one time If the subject has bad side effects the doctor may tell himher not to take the lenalidomide for a short time period or may be removed from the study Otherwise the subject will continue daily dosing with Lenalidomide for approximately 1 year until four weeks after the final vaccine
Four weeks after the subject starts the Lenalidomide she will start to receive hisher vaccines The vaccine will be injected under the skin also called subcutaneously Normally the subject will have the shots as an outpatient no overnight stay in the hospital will be required She will receive the first five 5 shots at 2 week intervals She will then receive eleven 11 shots at 4 weekly intervals In total the subject may receive up to sixteen 16 shots over a period of one year As with the Lenalidomide if the subject has bad side effects she may not receive hisher vaccines for a short period of time or may be removed from the study Otherwise the subject will receive the vaccines on the schedule as specified earlier in this paragraph These shots must be given at Houston Methodist Hospital
Following these injections the doctor will follow the subject for 1 year after the last shot to see how the subject is doing
TESTS DURING AND AFTER EXPERIMENTAL TREATMENT
A complete history and physical examination is necessary before the subject can be enrolled in the study A physical examination will also be performed each time she receives a shot of the modified cells The place on the subjects body where she had received the shots will be examined during the physical exam
Research Blood Samples
Blood will be taken from a tube placed into the vein IV We will take blood samples at the following time points at study entry week 0 when the subject starts Lenalidomide weeks 2 4 6 8 10 and 16 and then every 4 weeks until week 60 The last blood sample will be at one year after the last shot We will do this to make sure that the Lenalidomide is working correctly and to study how the modified cells are working in the body
The amount of blood that will be obtained each time is approximately 2-3 tablespoonfuls which is considered to be a safe amount If the subject has a central line an IV line that has been placed in a large blood vessel that is meant to be used for long periods of time the blood will be taken from it so that extra sticks should not be needed Additional office visits may be necessary to obtain this blood The maximum total amount of blood to be collected from the subject is 40-60 tablespoons
Other tests If the subject is a woman who can get pregnant she will have pregnancy counseling and urine tests as long as she is taking lenalidomide
In order to participate in this study the subject must register into and follow the requirements of the Revlimid REMS program of Celgene Corporation the company that supplies Lenalidomide This program provides education and counseling on the risks of fetal exposure blood clots and reduced blood counts that can occur when taking Lenalidomide The subject will be required to receive counseling every 28 days during treatment with lenalidomide follow the pregnancy testing and birth control requirements of the program that are appropriate for himher and take telephone surveys regarding your compliance with the program Participating in the Revlimid REMS program is a study requirement
The rest of the cancer cells have been stimulated to express on their surface a substance called the human CD40L These substances IL-2 and CD40L already naturally present in the body are meant to help the immune system fight the cancer
At the point that the doctor feels the subject should begin treatment on this protocol the treatment will be as follows
The subject will begin taking Allopurinol by mouth at 300 mg and will continue taking Allopurinol daily for 14 days Allopurinol is also called Zyloprim and it will be taken to prevent tumor lysis syndrome Tumor lysis syndrome can be a serious condition that occurs sometimes when cancer treatment is started Tumor lysis syndrome can cause other medical problems
Two days after Allopurinol was started the subject will begin taking Lenalidomide The Lenalidomide dose will be 5 mg taken by mouth daily The subject should swallow the capsules whole with water at the same time each day and should not break chew or open the capsules Females of childbearing potential who are caring for the subject should not touch the lenalidomide capsules or bottles without gloves If a dose of lenalidomide is missed it should be taken as soon as possible on the same day If it is missed for the entire day it should not be made up If more than the prescribed dose is taken of lenalidomide and the subject feels poorly she should seek emergency medical care and tell the study staff right away The subject will get 1 cycle of drug per month A max of a 28-day supply of the drug will be provided at one time If the subject has bad side effects the doctor may tell himher not to take the lenalidomide for a short time period or may be removed from the study Otherwise the subject will continue daily dosing with Lenalidomide for approximately 1 year until four weeks after the final vaccine
Four weeks after the subject starts the Lenalidomide she will start to receive hisher vaccines The vaccine will be injected under the skin also called subcutaneously Normally the subject will have the shots as an outpatient no overnight stay in the hospital will be required She will receive the first five 5 shots at 2 week intervals She will then receive eleven 11 shots at 4 weekly intervals In total the subject may receive up to sixteen 16 shots over a period of one year As with the Lenalidomide if the subject has bad side effects she may not receive hisher vaccines for a short period of time or may be removed from the study Otherwise the subject will receive the vaccines on the schedule as specified earlier in this paragraph These shots must be given at Houston Methodist Hospital
Following these injections the doctor will follow the subject for 1 year after the last shot to see how the subject is doing
TESTS DURING AND AFTER EXPERIMENTAL TREATMENT
A complete history and physical examination is necessary before the subject can be enrolled in the study A physical examination will also be performed each time she receives a shot of the modified cells The place on the subjects body where she had received the shots will be examined during the physical exam
Research Blood Samples
Blood will be taken from a tube placed into the vein IV We will take blood samples at the following time points at study entry week 0 when the subject starts Lenalidomide weeks 2 4 6 8 10 and 16 and then every 4 weeks until week 60 The last blood sample will be at one year after the last shot We will do this to make sure that the Lenalidomide is working correctly and to study how the modified cells are working in the body
The amount of blood that will be obtained each time is approximately 2-3 tablespoonfuls which is considered to be a safe amount If the subject has a central line an IV line that has been placed in a large blood vessel that is meant to be used for long periods of time the blood will be taken from it so that extra sticks should not be needed Additional office visits may be necessary to obtain this blood The maximum total amount of blood to be collected from the subject is 40-60 tablespoons
Other tests If the subject is a woman who can get pregnant she will have pregnancy counseling and urine tests as long as she is taking lenalidomide
In order to participate in this study the subject must register into and follow the requirements of the Revlimid REMS program of Celgene Corporation the company that supplies Lenalidomide This program provides education and counseling on the risks of fetal exposure blood clots and reduced blood counts that can occur when taking Lenalidomide The subject will be required to receive counseling every 28 days during treatment with lenalidomide follow the pregnancy testing and birth control requirements of the program that are appropriate for himher and take telephone surveys regarding your compliance with the program Participating in the Revlimid REMS program is a study requirement
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None