Ignite Creation Date:
2024-05-05 @ 5:18 PM
Last Modification Date:
2024-10-26 @ 9:30 AM
Study NCT ID:
NCT00427791
Status:
COMPLETED
Last Update Posted:
2016-05-09
First Post:
2007-01-25
Brief Title:
Rituximab to the Preparative Regimen of Etoposide and Total Body Irradiation in Acute Lymphoblastic Leukemia
Sponsor:
MD Anderson Cancer Center
Organization:
MD Anderson Cancer Center
Study Overview
Official Title:
Phase II Randomized Study Evaluating the Addition of Rituximab to the Preparative Regimen of Etoposide and Total Body Irradiation in Acute Lymphoblastic Leukemia
Status:
COMPLETED
Status Verified Date:
2012-04
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:
None
Brief Summary:
Primary Objective
To determine the progression free survival PFS of the preparative regimen rituximab etoposide and total body irradiation TBI in patients with acute lymphoblastic leukemia ALL receiving allogeneic hematopoietic stem cell transplantation SCT
Secondary Objectives
To determine the effect of rituximab on the incidence of acute graft vs host disease GVHD
To determine the efficacy of adding imatinib mesylate post transplant in ALL patients with the t922q34q11 cytogenetic abnormality
To estimate the probability of molecular complete remission at one year for the described treatment approach as determined by serial minimal residual disease MRD monitoring
To determine the rate of GVHD engraftment toxicity and overall survival OS for this treatment regimen
To determine the progression free survival PFS of the preparative regimen rituximab etoposide and total body irradiation TBI in patients with acute lymphoblastic leukemia ALL receiving allogeneic hematopoietic stem cell transplantation SCT
Secondary Objectives
To determine the effect of rituximab on the incidence of acute graft vs host disease GVHD
To determine the efficacy of adding imatinib mesylate post transplant in ALL patients with the t922q34q11 cytogenetic abnormality
To estimate the probability of molecular complete remission at one year for the described treatment approach as determined by serial minimal residual disease MRD monitoring
To determine the rate of GVHD engraftment toxicity and overall survival OS for this treatment regimen
Detailed Description:
Disease relapse and GVHD are 2 factors that significantly impact survival in ALL patients who receive SCT GVHD occurs when donor cells graft attack the stem cell recipients hosts cells The term acute refers to the time it takes for the GVHD to appear after the transplant This time frame is usually within the first 100 days after the transplant GVHD occurs in up to 50 of patients who receive a transplant
Etoposide is a traditional chemotherapy drug that is designed to interfere with the production of cancer cells at the DNA and RNA level Total body irradiation TBI uses low level radiation to also interfere with the production of cancer cells at the DNA and RNA level The combination of etoposide and TBI is a standard transplant conditioning therapy used for ALL patients Rituximab is a monoclonal antibody that is designed to work against cells that express the antigen CD20 In addition some studies suggest that it may decrease the risk of GVHD
Before you can start treatment on this study you will have what are called screening tests These tests will help the doctor decide if you are eligible to take part in the study You will have a complete medical history and physical exam including routine blood 2-3 teaspoons and urine tests You will have a chest x-ray heart scan echocardiogram or MUGA scan Multi Gated Acquisition Scan lung function test and a bone marrow biopsy with aspirate to evaluate the status of your disease before transplant To collect a bone marrow biopsy and aspirate an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow and bone is withdrawn through a large needle A bone marrow core a solid piece from the bone marrow is also collected through a hollow needle inserted into the hip bone Women who are able to have children must have a negative blood pregnancy test
If you are found to be eligible to take part in this study you will be randomly assigned as in the toss of a coin to one of 2 treatment groups Participants in one group will receive etoposide and TBI before their transplant Participants in the other group will receive etoposide TBI and rituximab before their transplant There is an equal chance of being assigned to either group You will receive treatment on this study as an inpatient
On the 1st day of hospitalization you will receive fluids by vein through a central venous catheter a plastic tube inserted into a large vein under your collar bone You will receive TBI once a day for the next 4 days During TBI you will lie flat on a table and receive radiation beams to all parts of the body with shielding over certain parts of the body On the following day you will receive etoposide through the catheter over 4 hours You will then have 2 days of rest followed by your transplant of stem cells The stem cells will be infused into your vein The infusion can last from 30 minutes to several hours
If you are assigned to the rituximab group you will also receive rituximab once a week for 4 weeks by vein over 4-8 hours The first dose will be given on the first day you receive etoposide If you are receiving a mismatched-related allogeneic stem cell transplant or an unrelated allogeneic stem cell transplant you will also receive Thymoglobulin by vein on the 3 days before the stem cell infusion This is given to decrease the risk of GVHD and graft rejection in mismatched transplants
In addition you may receive a supportive care drug called palifermin Kepivance which is a human keratinocyte growth factor KGF produced by recombinant DNA technology in E coli Its use has been shown to decrease mucositis resulting from high dose chemotherapy used in stem cell transplantation You may receive palifermin for 3 days before starting radiation therapy and for 2 days beginning on the day of your stem cell infusion You may not receive palifermin but you will still receive transplant
After you blood counts have normalized following your stem cell transplant you will start taking imatinib mesylate by mouth only if your disease has the Philadelphia chromosome Ph ALL Approximately 25-30 of adults with ALL harbor the Philadelphia chromosome You will take it once a day until 1 year after your transplant Imatinib mesylate should be taken with a meal and a glass of water preferably in the morning The dose will be gradually increased as long as you dont experience severe side effects If severe side effects occur imatinib will be stopped either temporarily or permanently
You will receive several other medications to help the treatment work and to help decrease the risk of infections while your immune system is weak Tacrolimus and methotrexate will be given to decrease the risk of GVHD The tacrolimus will be started on the day before the transplant and will continue for up to 6 months Tacrolimus is given by vein at first and then by mouth when you are able to eat Methotrexate is given by vein on Days 1 3 6 and 11 after the transplant
Sulfamethoxazole Bactrim or pentamidine will be given to fight bacteria Bactrim is given by mouth when your blood counts are good Pentamidine is given by vein when the counts are low Acyclovir will be given at first by vein and then Valtrex valacyclovir will be given by mouth to decrease the risk of viral infections Both of these will be given as per standard of care Granulocyte colony-stimulating factor G-CSF will be given to help the new bone marrow grow It is given as an injection under the skin after the transplant It will continue until the white blood cells reach an acceptable level These are all routine supportive medications used during bone marrow transplantation Overall some of these drugs will be given for as long as 6 months or possibly longer Other medications may be necessary If you are allergic to some of these drugs changes will be made
You will be in the hospital for about 3-4 weeks You will have checkups every day until you are discharged from the hospital You will then be seen in the outpatient clinic at least 3 times a week until your blood counts improve You will be seen by your doctor at least every week until 100 days after the bone marrow transplant You must stay in Houston during this time After 100 days you will be required to return to Houston every 3 months for tests and evaluation over the next 2 years At these visits you will have blood about 2-3 teaspoons collected for routine tests You will also have a bone marrow biopsy
Some participants may need to receive spinal taps with chemotherapy methotrexate or cytarabine given through the spine several times over the year after transplantation This is only for patients with a previous clinical history of leukemic involvement of the brain or high risk of developing leukemia relapse in the brain The spinal tap is performed in the clinic If you are one of these participants you will be given local anesthetic at the lower back site where a small needle will be inserted in the space between 2 spinal bones A small amount of fluid that bathes the brain cerebrospinal fluid will be removed for testing and a small amount of chemotherapy will be given
This is an investigational study The FDA has approved all of the drugs used in this study for use in stem cell transplantation However their use together in this study is experimental Up to 80 patients will take part in this study All will be enrolled at UT MD Anderson Cancer Center
Etoposide is a traditional chemotherapy drug that is designed to interfere with the production of cancer cells at the DNA and RNA level Total body irradiation TBI uses low level radiation to also interfere with the production of cancer cells at the DNA and RNA level The combination of etoposide and TBI is a standard transplant conditioning therapy used for ALL patients Rituximab is a monoclonal antibody that is designed to work against cells that express the antigen CD20 In addition some studies suggest that it may decrease the risk of GVHD
Before you can start treatment on this study you will have what are called screening tests These tests will help the doctor decide if you are eligible to take part in the study You will have a complete medical history and physical exam including routine blood 2-3 teaspoons and urine tests You will have a chest x-ray heart scan echocardiogram or MUGA scan Multi Gated Acquisition Scan lung function test and a bone marrow biopsy with aspirate to evaluate the status of your disease before transplant To collect a bone marrow biopsy and aspirate an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow and bone is withdrawn through a large needle A bone marrow core a solid piece from the bone marrow is also collected through a hollow needle inserted into the hip bone Women who are able to have children must have a negative blood pregnancy test
If you are found to be eligible to take part in this study you will be randomly assigned as in the toss of a coin to one of 2 treatment groups Participants in one group will receive etoposide and TBI before their transplant Participants in the other group will receive etoposide TBI and rituximab before their transplant There is an equal chance of being assigned to either group You will receive treatment on this study as an inpatient
On the 1st day of hospitalization you will receive fluids by vein through a central venous catheter a plastic tube inserted into a large vein under your collar bone You will receive TBI once a day for the next 4 days During TBI you will lie flat on a table and receive radiation beams to all parts of the body with shielding over certain parts of the body On the following day you will receive etoposide through the catheter over 4 hours You will then have 2 days of rest followed by your transplant of stem cells The stem cells will be infused into your vein The infusion can last from 30 minutes to several hours
If you are assigned to the rituximab group you will also receive rituximab once a week for 4 weeks by vein over 4-8 hours The first dose will be given on the first day you receive etoposide If you are receiving a mismatched-related allogeneic stem cell transplant or an unrelated allogeneic stem cell transplant you will also receive Thymoglobulin by vein on the 3 days before the stem cell infusion This is given to decrease the risk of GVHD and graft rejection in mismatched transplants
In addition you may receive a supportive care drug called palifermin Kepivance which is a human keratinocyte growth factor KGF produced by recombinant DNA technology in E coli Its use has been shown to decrease mucositis resulting from high dose chemotherapy used in stem cell transplantation You may receive palifermin for 3 days before starting radiation therapy and for 2 days beginning on the day of your stem cell infusion You may not receive palifermin but you will still receive transplant
After you blood counts have normalized following your stem cell transplant you will start taking imatinib mesylate by mouth only if your disease has the Philadelphia chromosome Ph ALL Approximately 25-30 of adults with ALL harbor the Philadelphia chromosome You will take it once a day until 1 year after your transplant Imatinib mesylate should be taken with a meal and a glass of water preferably in the morning The dose will be gradually increased as long as you dont experience severe side effects If severe side effects occur imatinib will be stopped either temporarily or permanently
You will receive several other medications to help the treatment work and to help decrease the risk of infections while your immune system is weak Tacrolimus and methotrexate will be given to decrease the risk of GVHD The tacrolimus will be started on the day before the transplant and will continue for up to 6 months Tacrolimus is given by vein at first and then by mouth when you are able to eat Methotrexate is given by vein on Days 1 3 6 and 11 after the transplant
Sulfamethoxazole Bactrim or pentamidine will be given to fight bacteria Bactrim is given by mouth when your blood counts are good Pentamidine is given by vein when the counts are low Acyclovir will be given at first by vein and then Valtrex valacyclovir will be given by mouth to decrease the risk of viral infections Both of these will be given as per standard of care Granulocyte colony-stimulating factor G-CSF will be given to help the new bone marrow grow It is given as an injection under the skin after the transplant It will continue until the white blood cells reach an acceptable level These are all routine supportive medications used during bone marrow transplantation Overall some of these drugs will be given for as long as 6 months or possibly longer Other medications may be necessary If you are allergic to some of these drugs changes will be made
You will be in the hospital for about 3-4 weeks You will have checkups every day until you are discharged from the hospital You will then be seen in the outpatient clinic at least 3 times a week until your blood counts improve You will be seen by your doctor at least every week until 100 days after the bone marrow transplant You must stay in Houston during this time After 100 days you will be required to return to Houston every 3 months for tests and evaluation over the next 2 years At these visits you will have blood about 2-3 teaspoons collected for routine tests You will also have a bone marrow biopsy
Some participants may need to receive spinal taps with chemotherapy methotrexate or cytarabine given through the spine several times over the year after transplantation This is only for patients with a previous clinical history of leukemic involvement of the brain or high risk of developing leukemia relapse in the brain The spinal tap is performed in the clinic If you are one of these participants you will be given local anesthetic at the lower back site where a small needle will be inserted in the space between 2 spinal bones A small amount of fluid that bathes the brain cerebrospinal fluid will be removed for testing and a small amount of chemotherapy will be given
This is an investigational study The FDA has approved all of the drugs used in this study for use in stem cell transplantation However their use together in this study is experimental Up to 80 patients will take part in this study All will be enrolled at UT MD Anderson Cancer Center
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