Azacitidine (AZA) in Minimal Residual Disease (MRD) Chronic Myeloid Leukemia (CML)
This is a two part study. The goal of the first part of this clinical research study is to find the highest tolerable dose of azacitidine that can be given with a tyrosine kinase inhibitor (TKI) that you are already taking (such as Gleevec, Sprycel, or Tasigna). The safety of this drug will also be studied. The goal of the second part is to see if this combination may improve your response to the TKI you are already taking.
Azacitidine is designed to change genes that are thought to cause leukemia. By changing these genes, the drug may help to stop them from causing the disease to grow.
Drug: Azacitidine (AZA)
Drug: Tyrosine kinase inhibitor (TKI)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I-II Study of Low-Dose Azacitidine (Vidaza) in Patients With Chronic Myeloid Leukemia Who Have Minimal Residual Disease While Receiving Therapy With Tyrosine Kinase Inhibitors (VZ-CML-PI-0236)|
- Maximum tolerated dose (MTD) of Azacitidine [ Time Frame: First 28 day cycle ] [ Designated as safety issue: No ]MTD is defined as the highest dose level in which 6 patients have been treated and one or fewer patient experiences Dose-Limiting Toxicity (DLT) within the first course of treatment.
- Number of participants with decrease of transcript levels by at least one log (or undetectable transcript level) within 12 months [ Time Frame: Baseline to 12 months ] [ Designated as safety issue: No ]Participants with response defined as a greater than a one-log reduction of BCR-ABL transcript levels from the baseline level at the time vaccination was initiated, or a disappearance of BCR-ABL transcripts (i.e., complete molecular response) within 12 months.
|Study Start Date:||August 2012|
|Estimated Primary Completion Date:||August 2017 (Final data collection date for primary outcome measure)|
Experimental: Dose Escalation Group (AZA)
Azacitidine (AZA) starting dose 50 mg/m2 a day for 3 days subcutaneous or intravenous of 28 day cycle. TKI at dose received during last 6 months.
Drug: Azacitidine (AZA)
Starting Dose 50 mg/m2 by subcutaneous or by vein for 3 days of a 28 day cycle.
Other Names:Drug: Tyrosine kinase inhibitor (TKI)
Continuation of dose already receiving during previous 6 months.
Experimental: Expansion Group (AZA MTD)
Dose Escalation Group plus additional 36 participants for Azacitidine 75 mg/m2 (or Phase I MTD) either subcutaneous or intravenous every day for 3 days of 28 day cycle. TKI at dose received during last 6 months.
Drug: Tyrosine kinase inhibitor (TKI)
Continuation of dose already receiving during previous 6 months.Drug: Azacitidine
75 mg/m2 daily for 3 days, unless MTD defined at lower dose level in Phase I then that would become dose used for Phase II.
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Study Drug Administration:
If you are found to be eligible to take part in this study, you will continue receiving the same TKI at the dose you had been receiving for the last 6 months.
You will receive azacitidine either as an injection under your skin or through a vein every day for 3 to 7 days of each 28-day cycle. The dose and how often you take the drug will depend on when you enter the study. The study staff will tell you how often you will receive the drug.
In the first part of the study, you will be assigned to a dose level of azacitidine based on when you join this study. Up to 2 dose levels of azacitidine will be tested. At least 3 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level. The next group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of azacitidine is found. This is called the Dose Escalation Group.
Once the highest tolerated dose has been found, an extra 36 participants will receive azacitidine at this dose level. This is called the Expansion Group.
If you have severe side effects from the study drug, the study doctor may decide to reduce and/or stop drug dosing until your side effects improve. If the doctor thinks it is in you best interest, your dose may be increased.
At every visit, you will be asked about any side effects you have had and to list any drugs you may be taking.
- Every 1-2 weeks for 8 weeks, then at the start of every cycle, blood (about 1 teaspoon) will be drawn for routine tests.
- Every 2-4 weeks for 8 weeks, then before each cycle, blood (about 1 teaspoon) will also be drawn to test your kidney and liver function.
- Before each cycle for 3 cycles, then every 3-6 cycles until 1 year, then every 6-12 cycles, blood (about 1 tablespoon) drawn for molecular testing.
- Every 3-6 months in Year 1, then as often the doctor thinks it is needed, you will have a bone marrow aspirate to check the status of the disease.
- If you are in the Expansion Group, every 3 months (+/- 1 month) for the first 6 months, then every 6-12 months, you will have a complete physical exam.
- If you are in the Dose Escalation Group, every 2 weeks for the first month, Months 1, 2, 3, and 6 (+/- 1 month), and then every 6-12 months, you will have a complete physical exam.
Length of Study:
You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
Your participation on the study will be over once you have completed the end-of-treatment and follow-up visits.
This is an investigational study. TKIs are approved for the treatment of Chronic Myeloid Leukemia (CML). Azacitidine is FDA approved and commercially available for the treatment of patients with MDS. The combination of these drugs to treat CML is investigational.
Up to 48 patients will take part in this study. All will be enrolled at MD Anderson.
|United States, Texas|
|UT MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Jorge Cortes, MD||UT MD Anderson Cancer Center|