Ignite Creation Date:
2024-05-05 @ 5:26 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00452374
Status:
COMPLETED
Last Update Posted:
2011-11-02
First Post:
2007-03-23
Brief Title:
Oxaliplatin Fludarabine Cytarabine and Rituximab in Richters Syndrome Refractory CLL and PLL
Sponsor:
MD Anderson Cancer Center
Organization:
MD Anderson Cancer Center
Study Overview
Official Title:
A Phase I-II Study of Oxaliplatin Fludarabine Cytarabine and Rituximab in Patients With Richters Transformation Prolymphocytic Leukemia or RefractoryRelapsed B-Cell Chronic Lymphocytic Leukemia
Status:
COMPLETED
Status Verified Date:
2011-10
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 Objectives
1 Determine the maximum tolerated dose MTD and dose-limiting toxicity DLT of oxaliplatin in combination with fludarabine Ara-C and rituximab in patients with Richters transformation prolymphocytic leukemia PLL or refractoryrelapsed B-cell chronic lymphocytic leukemia CLL
2 Assess the complete response CR and partial response PR rate to combination therapy of oxaliplatin fludarabine Ara-C and rituximab in patients with Richters transformation PLL or refractoryrelapsed B-cell CLL
3 Determine the safety and toxicity profile of combination therapy of oxaliplatin fludarabine Ara-C and rituximab in patients with Richters transformation PLL or refractoryrelapsed B-cell CLL
Secondary Objectives
1 Determine the duration of response failure-free survival and overall survival
2 Determine the incidence of infections bacterial fungal and viral in patients with Richters transformation prolymphocytic leukemia or refractoryrelapsed B-cell CLL treated with rituximab oxaliplatin fludarabine and Ara-C monitor immune parameters such as T cell counts and immunoglobulin levels and monitor Epstein-Barr virus EBV status
3 Characterize the pharmacodynamics of oxaliplatin in leukemia cells with respect to total adduct formation cross-link formation and excision deoxyribonucleic acid DNA responses Compare these parameters in cells from the same patient after treatment with oxaliplatin in combination with fludarabine and Ara-C
1 Determine the maximum tolerated dose MTD and dose-limiting toxicity DLT of oxaliplatin in combination with fludarabine Ara-C and rituximab in patients with Richters transformation prolymphocytic leukemia PLL or refractoryrelapsed B-cell chronic lymphocytic leukemia CLL
2 Assess the complete response CR and partial response PR rate to combination therapy of oxaliplatin fludarabine Ara-C and rituximab in patients with Richters transformation PLL or refractoryrelapsed B-cell CLL
3 Determine the safety and toxicity profile of combination therapy of oxaliplatin fludarabine Ara-C and rituximab in patients with Richters transformation PLL or refractoryrelapsed B-cell CLL
Secondary Objectives
1 Determine the duration of response failure-free survival and overall survival
2 Determine the incidence of infections bacterial fungal and viral in patients with Richters transformation prolymphocytic leukemia or refractoryrelapsed B-cell CLL treated with rituximab oxaliplatin fludarabine and Ara-C monitor immune parameters such as T cell counts and immunoglobulin levels and monitor Epstein-Barr virus EBV status
3 Characterize the pharmacodynamics of oxaliplatin in leukemia cells with respect to total adduct formation cross-link formation and excision deoxyribonucleic acid DNA responses Compare these parameters in cells from the same patient after treatment with oxaliplatin in combination with fludarabine and Ara-C
Detailed Description:
Oxaliplatin fludarabine cytarabine and rituximab are anticancer drugs Oxaliplatin is a platinum compound that has been shown to be effective in fighting other cancers Oxaliplatin is a third generation platinum compound with higher activity and less toxicity in colon cancer and other tumors compared to other platinum compounds such as cisplatin Oxaliplatin has shown activity in patients with relapsed or refractory non-Hodgkins lymphoma
Before treatment starts you will have a complete physical exam and routine blood tests about 2 teaspoons A bone marrow sample will be collected To collect a bone marrow sample an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle Women who are able to have children must have a negative blood or urine pregnancy test
This research study has two parts a Phase I part and a Phase II part You will receive at least 1 cycle of therapy
Oxaliplatin will be given through a needle in your vein called an IV for 4 days Days 1 through 4 Rituximab will be given through an IV on Day 3 of the first cycle and on Day 1 on every cycle after that One day after the first dose of oxaliplatin and rituximab Day 2 fludarabine and cytarabine will be given through an IV for two days Days 2 and 3 Peg-filgrastim will be given subcutaneously through a needle just under your skin on Day 6 Other IV fluids such as saline will be given on all of the treatment days to keep you from being dehydrated which means that the daily visit may take eight hours The combination will be repeated once a cycle every 28 days for up to a total of 6 cycles
During the Phase I and II phases of the study researchers will be testing different dose levels of the study drug combination Three patients will be enrolled at each dose level Each time the dose level is raised it will occur after each patient has been monitored for 28 days Individual patients who do not experience serious drug-related side effects after the second cycle may receive the next higher dose level for the following treatment cycles
Drugs will be given before each dose of rituximab to lower the risk of side effects If side effects do occur during rituximab treatment rituximab may have to be stopped until the side effects go away and then restarted This may make your time in the outpatient area longer
The first treatment cycle will be given at M D Anderson Depending on your response to treatment up to 5 more cycles can be performed either at M D Anderson or at home with your regular physician After 3 cycles of treatment you will be checked at M D Anderson to see if the disease is responding to treatment If the disease is responding after 3 cycles of therapy you may continue to receive therapy for up to 3 more cycles If the disease is not responding you will be taken off the study and your doctor will discuss other treatment options with you
Once the best safe dose of the drug combination is found in the Phase I portion of the study the next group of participants entering the study will take part in the Phase II portion of the study The goal of this part of the study is to look at the effects of the drug combination in patients with refractory CLL prolymphocytic leukemia or Richters transformation The dose level for the combination will be the one found in the Phase I part of the study
The same dose levels for all four drugs will be used throughout the Phase II portion of the study unless intolerable side effects occur In that case the dose may be lowered or the treatment may be stopped You will be taken off study if the disease gets worse
During each treatment cycle you will have blood samples about 1 teaspoon each taken once every 1-2 weeks Bone marrow biopsies will be done at the end of the 3rd and 6th chemotherapy cycles
After your last cycle of treatment is completed you will have blood drawn about 2 teaspoons each every 3 months for as long as you are in remission for routine testing
This is an investigational study The FDA has authorized the use of these drugs for research only when given for this purpose All of these drugs are commercially available for other types of treatment Oxaliplatin will be free of charge during the study You andor your insurance company will be responsible for the cost of the other drugs used in this study Patients will be enrolled at M D Anderson University of California San Diego or Dana-Farber Cancer Institute Up to 52 patients will take part in this multicenter study The estimated number of patients who will be treated at M D Anderson is up to 52
Before treatment starts you will have a complete physical exam and routine blood tests about 2 teaspoons A bone marrow sample will be collected To collect a bone marrow sample an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle Women who are able to have children must have a negative blood or urine pregnancy test
This research study has two parts a Phase I part and a Phase II part You will receive at least 1 cycle of therapy
Oxaliplatin will be given through a needle in your vein called an IV for 4 days Days 1 through 4 Rituximab will be given through an IV on Day 3 of the first cycle and on Day 1 on every cycle after that One day after the first dose of oxaliplatin and rituximab Day 2 fludarabine and cytarabine will be given through an IV for two days Days 2 and 3 Peg-filgrastim will be given subcutaneously through a needle just under your skin on Day 6 Other IV fluids such as saline will be given on all of the treatment days to keep you from being dehydrated which means that the daily visit may take eight hours The combination will be repeated once a cycle every 28 days for up to a total of 6 cycles
During the Phase I and II phases of the study researchers will be testing different dose levels of the study drug combination Three patients will be enrolled at each dose level Each time the dose level is raised it will occur after each patient has been monitored for 28 days Individual patients who do not experience serious drug-related side effects after the second cycle may receive the next higher dose level for the following treatment cycles
Drugs will be given before each dose of rituximab to lower the risk of side effects If side effects do occur during rituximab treatment rituximab may have to be stopped until the side effects go away and then restarted This may make your time in the outpatient area longer
The first treatment cycle will be given at M D Anderson Depending on your response to treatment up to 5 more cycles can be performed either at M D Anderson or at home with your regular physician After 3 cycles of treatment you will be checked at M D Anderson to see if the disease is responding to treatment If the disease is responding after 3 cycles of therapy you may continue to receive therapy for up to 3 more cycles If the disease is not responding you will be taken off the study and your doctor will discuss other treatment options with you
Once the best safe dose of the drug combination is found in the Phase I portion of the study the next group of participants entering the study will take part in the Phase II portion of the study The goal of this part of the study is to look at the effects of the drug combination in patients with refractory CLL prolymphocytic leukemia or Richters transformation The dose level for the combination will be the one found in the Phase I part of the study
The same dose levels for all four drugs will be used throughout the Phase II portion of the study unless intolerable side effects occur In that case the dose may be lowered or the treatment may be stopped You will be taken off study if the disease gets worse
During each treatment cycle you will have blood samples about 1 teaspoon each taken once every 1-2 weeks Bone marrow biopsies will be done at the end of the 3rd and 6th chemotherapy cycles
After your last cycle of treatment is completed you will have blood drawn about 2 teaspoons each every 3 months for as long as you are in remission for routine testing
This is an investigational study The FDA has authorized the use of these drugs for research only when given for this purpose All of these drugs are commercially available for other types of treatment Oxaliplatin will be free of charge during the study You andor your insurance company will be responsible for the cost of the other drugs used in this study Patients will be enrolled at M D Anderson University of California San Diego or Dana-Farber Cancer Institute Up to 52 patients will take part in this multicenter study The estimated number of patients who will be treated at M D Anderson is up to 52
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