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Fludarabine, Cytarabine, Filgrastim and Idarubicin in Core Binding Factor (CBF) Leukemias
Conditions
Acute Myelogenous Leukemia
Conditions: official terms
Leukemia - Leukemia, Myeloid - Leukemia, Myeloid, Acute
Conditions: Keywords
Leukemia, Acute Myelogenous Leukemia, AML
Study Type
Interventional
Study Phase
Phase 2
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: Fludarabine
Type: Drug
Name: Cytarabine
Type: Drug
Name: G-CSF (Filgrastim, Neupogen)
Type: Drug
Name: Idarubicin
Type: Drug
Overall Status
Recruiting
Summary
The goal of this clinical research study is to learn if idarubicin can be added to the combination of fludarabine, cytarabine, and Neupogen (Filgrastim) without increasing the risk of side effects. This study will also look at whether the addition of idarubicin will increase the long-term chances of patients remaining disease free.
Detailed Description
The Study Drugs:
Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic material of cells). This may increase the likelihood of the cells dying.
Cytarabine is designed to insert itself into DNA and stop the DNA from repairing itself.
Filgrastim promotes the growth of white blood cells, which help to fight infections.
Decitabine and Idarubicin are designed to damage the DNA (the genetic material) of cells, which may cause cancer cells to die.
Parts of the Study:
There will be 2 parts to this study. The first part of the study is called induction therapy. During induction, the study doctor will try to get rid of the leukemia cells from your bone marrow. If induction causes the leukemia cells to be removed from your bone marrow and your blood counts return to normal, you will be in remission. Induction usually lasts 4-6 weeks.
If you are in remission, you will begin the second part of the study, called post-remission therapy. You will receive up to 4-6 cycles (1 cycle every 4-6 weeks) of post-remission therapy, depending on your blood counts. Each study cycle lasts 4-6 weeks.
Study Drug Administration:
If you are found to be eligible to take part in this study, during induction therapy, you will be given fludarabine and cytarabine through a needle in your vein every day, for 5 days in a row (Days 1-5). You will receive fludarabine over 30 minutes and cytarabine over 4 hours.
Filgrastim will be given one time daily as an injection just under the skin starting on the day before you receive fludarabine and cytarabine, and you will continue to receive filgrastim one time daily until your white blood cell count is near normal.
You will receive idarubicin through a needle in your vein over 30 minutes on Days 3 and 4 right after you receive fludarabine.
During post-remission therapy, you will receive fludarabine and cytarabine for 3 days (Days 1-3) instead of 5 days. You will receive idarubicin at the same dose as given during induction therapy on Days 2 and 3. You will receive idarubicin one time during Cycles 3-6 during post-remission therapy. You will receive filgrastim one time on the day before each post-remission cycle.
During post-remission therapy, you may begin receiving decitabine instead of fludarabine, cytarabine, filgrastim, and/or idarubicin if you are 60 years or older, or if you have had intolerable side effects. If the doctor thinks it is in your best interest, you will begin receiving decitabine infusions over 1 hour, for 5 days in a row, every 4-6 weeks for up to 12 cycles. The doctor will discuss this with you.
Study Visits:
During induction therapy, blood (about 2 teaspoons) will be drawn at least once a week for routine testing.
After 3 weeks (Between Days 18-24), you will have a bone marrow aspirate to check the status of the disease. If the leukemia cells are not completely gone from your bone marrow by the end of 3 weeks, your study doctor may decide to repeat the test.
If the repeat bone marrow aspirate shows that you are not in remission, your study doctor may decide to give you another cycle of induction therapy.
Once you begin post-remission therapy, you will have the following tests and procedures:
- You will have a physical exam, including measurement of your vital signs, including your weight.
- You will be asked how well you are able to perform the normal activities of daily living (performance status).
- Blood (about 2 teaspoons) will be drawn for routine blood tests.
At Months 4 and 7, you will have a bone marrow aspirate to check the status of the disease.
Part of the bone marrow sample collected at these bone marrow aspirations will be sent to the M. D. Anderson molecular lab for testing.
If your study doctor thinks it is necessary, you may have a bone marrow aspirate after the first 7 months to check the status of the disease.
Length of Study:
You will be on study for one cycle of induction therapy and up to 6 cycles of post-remission therapy. You will be taken off study if the disease gets worse or intolerable side effects occur.
Long-term follow up:
You will have blood (about 2 teaspoons) drawn for routine testing every 6 months for 2 years after the study.
This is an investigational study. Cytarabine is FDA approved and commercially available for the treatment of AML. Fludarabine is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL). Filgrastim is FDA approved and commercially available to treat fever associated with low white cell counts in patients with AML. Idarubicin is FDA approved and commercially available for the treatment of acute leukemias, lymphomas, Hodgkin's disease and breast cancer. At this time, their use in combination is for research purposes only.
Decitabine is FDA approved for treatment of myelodysplastic syndrome and is commercially available.
Up to 180 patients will take part in this study. All will be enrolled at MD Anderson.
Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic material of cells). This may increase the likelihood of the cells dying.
Cytarabine is designed to insert itself into DNA and stop the DNA from repairing itself.
Filgrastim promotes the growth of white blood cells, which help to fight infections.
Decitabine and Idarubicin are designed to damage the DNA (the genetic material) of cells, which may cause cancer cells to die.
Parts of the Study:
There will be 2 parts to this study. The first part of the study is called induction therapy. During induction, the study doctor will try to get rid of the leukemia cells from your bone marrow. If induction causes the leukemia cells to be removed from your bone marrow and your blood counts return to normal, you will be in remission. Induction usually lasts 4-6 weeks.
If you are in remission, you will begin the second part of the study, called post-remission therapy. You will receive up to 4-6 cycles (1 cycle every 4-6 weeks) of post-remission therapy, depending on your blood counts. Each study cycle lasts 4-6 weeks.
Study Drug Administration:
If you are found to be eligible to take part in this study, during induction therapy, you will be given fludarabine and cytarabine through a needle in your vein every day, for 5 days in a row (Days 1-5). You will receive fludarabine over 30 minutes and cytarabine over 4 hours.
Filgrastim will be given one time daily as an injection just under the skin starting on the day before you receive fludarabine and cytarabine, and you will continue to receive filgrastim one time daily until your white blood cell count is near normal.
You will receive idarubicin through a needle in your vein over 30 minutes on Days 3 and 4 right after you receive fludarabine.
During post-remission therapy, you will receive fludarabine and cytarabine for 3 days (Days 1-3) instead of 5 days. You will receive idarubicin at the same dose as given during induction therapy on Days 2 and 3. You will receive idarubicin one time during Cycles 3-6 during post-remission therapy. You will receive filgrastim one time on the day before each post-remission cycle.
During post-remission therapy, you may begin receiving decitabine instead of fludarabine, cytarabine, filgrastim, and/or idarubicin if you are 60 years or older, or if you have had intolerable side effects. If the doctor thinks it is in your best interest, you will begin receiving decitabine infusions over 1 hour, for 5 days in a row, every 4-6 weeks for up to 12 cycles. The doctor will discuss this with you.
Study Visits:
During induction therapy, blood (about 2 teaspoons) will be drawn at least once a week for routine testing.
After 3 weeks (Between Days 18-24), you will have a bone marrow aspirate to check the status of the disease. If the leukemia cells are not completely gone from your bone marrow by the end of 3 weeks, your study doctor may decide to repeat the test.
If the repeat bone marrow aspirate shows that you are not in remission, your study doctor may decide to give you another cycle of induction therapy.
Once you begin post-remission therapy, you will have the following tests and procedures:
- You will have a physical exam, including measurement of your vital signs, including your weight.
- You will be asked how well you are able to perform the normal activities of daily living (performance status).
- Blood (about 2 teaspoons) will be drawn for routine blood tests.
At Months 4 and 7, you will have a bone marrow aspirate to check the status of the disease.
Part of the bone marrow sample collected at these bone marrow aspirations will be sent to the M. D. Anderson molecular lab for testing.
If your study doctor thinks it is necessary, you may have a bone marrow aspirate after the first 7 months to check the status of the disease.
Length of Study:
You will be on study for one cycle of induction therapy and up to 6 cycles of post-remission therapy. You will be taken off study if the disease gets worse or intolerable side effects occur.
Long-term follow up:
You will have blood (about 2 teaspoons) drawn for routine testing every 6 months for 2 years after the study.
This is an investigational study. Cytarabine is FDA approved and commercially available for the treatment of AML. Fludarabine is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia (CLL). Filgrastim is FDA approved and commercially available to treat fever associated with low white cell counts in patients with AML. Idarubicin is FDA approved and commercially available for the treatment of acute leukemias, lymphomas, Hodgkin's disease and breast cancer. At this time, their use in combination is for research purposes only.
Decitabine is FDA approved for treatment of myelodysplastic syndrome and is commercially available.
Up to 180 patients will take part in this study. All will be enrolled at MD Anderson.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:
1. Patients must have untreated AML, or high-risk MDS [refractory anemia with excess blasts, (RAEB), or RAEB "in transformation" (RAEB-t)] characterized by t(8;21), inv(16), or t(16;16).The presence of additional abnormalities is irrelevant.
2. Age equal to or greater than 18 years (the safety of GO in patients <18 years is not determined and advantage of fludarabine, cytarabine, idarubicin-based regimen in CBF leukemias in children is not demonstrated).
3. Patients must provide written consent.
4. Because of the high possibility of CR in CBF leukemias, participants will not be excluded based on performance status.For patients with Eastern Co-operative Oncology Group (ECOG) performance status >/= to 3 the dosing schedule will be discussed with study chairman.
5. Patients with organ dysfunction will not be excluded from the study. For patients with evidence of organ dysfunction (creatinine >/= 1.5, cardiac ejection fraction /=2 and AST/ALT >/= 3 times ULN, dose adjustments/omissions will be made.
6. Up to one cycle of prior induction therapy will be permitted to include patients in whom presence of "good-risk" cytogenetics was initially missed. If the patient is in remission from induction therapy, he/she will receive post-remission therapy. If the patient is not in remission then he/she will receive induction therapy.
7. Patients of child bearing potential should practice effective methods of contraception.
Exclusion Criteria:
1) Pregnant and lactating females will be excluded since the safety of GO or FLAG + Ida in pregnancy and lactation is unknown.
1. Patients must have untreated AML, or high-risk MDS [refractory anemia with excess blasts, (RAEB), or RAEB "in transformation" (RAEB-t)] characterized by t(8;21), inv(16), or t(16;16).The presence of additional abnormalities is irrelevant.
2. Age equal to or greater than 18 years (the safety of GO in patients <18 years is not determined and advantage of fludarabine, cytarabine, idarubicin-based regimen in CBF leukemias in children is not demonstrated).
3. Patients must provide written consent.
4. Because of the high possibility of CR in CBF leukemias, participants will not be excluded based on performance status.For patients with Eastern Co-operative Oncology Group (ECOG) performance status >/= to 3 the dosing schedule will be discussed with study chairman.
5. Patients with organ dysfunction will not be excluded from the study. For patients with evidence of organ dysfunction (creatinine >/= 1.5, cardiac ejection fraction /=2 and AST/ALT >/= 3 times ULN, dose adjustments/omissions will be made.
6. Up to one cycle of prior induction therapy will be permitted to include patients in whom presence of "good-risk" cytogenetics was initially missed. If the patient is in remission from induction therapy, he/she will receive post-remission therapy. If the patient is not in remission then he/she will receive induction therapy.
7. Patients of child bearing potential should practice effective methods of contraception.
Exclusion Criteria:
1) Pregnant and lactating females will be excluded since the safety of GO or FLAG + Ida in pregnancy and lactation is unknown.
Location
The University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States
Status: Recruiting
Contact: Gautam Borthakur, MD - 713-563-1586
Start Date
April 2007
Completion Date
April 2017
Sponsors
M.D. Anderson Cancer Center
Source
M.D. Anderson Cancer Center
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page