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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)

Phase 1/Phase 2
16 Years
Open (Enrolling)

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Trial Information

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)

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.

Study Visits:

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.

Inclusion Criteria:

1. Patients 16 years or older with Philadelphia chromosome (Ph)- or BCR/ABL-positive CML
(as determined by cytogenetics, FISH, or PCR).

2. Patients must have received FDA-approved TKI therapy for at least 18 months and not
have increased their dose of FDA-approved TKI in the last 6 months.

3. Phase II patients must be in complete cytogenetic remission. For the phase I portion
of the study, patients may be included without a complete cytogenetic remission
provided they are in chronic phase.

4. Phase II patients must have detectable BCR-ABL transcript levels meeting at least one
of the following criteria: Patient has never achieved a major molecular response, and
transcript levels have shown in at least two consecutive measures separated by at
least 1 month to have increased by any value, or Achieved a major molecular response
that has been lost with an increase in transcript levels by at least 1-log, confirmed
in two consecutive analyses separated by at least 1 month, or The patient has
received therapy for at least 2 years and does not have a sustained major molecular
response, or The patient has received therapy for at least 5 years and does not have
a sustained complete molecular response. Patients included in the phase I portion of
the study are eligible regardless of their level of BCR-ABL transcripts.

5. Patients must not have had a known continuous interruption of imatinib therapy of
greater than 14 days or for a total of 6 weeks in the 6 months prior to enrollment.

6. Patients must sign an informed consent indicating that they are aware of the
investigational nature of this study in keeping with the policies of the hospital.

7. ECOG performance status
8. Adequate organ function defined as: bilirubin < 2x upper limit of normal (ULN)
(unless associated with Gilbert's syndrome), and ALT or AST
9. ANC >/=1 *10(9)/L and platelets >/= 50 *10(9)/L.

10. Serum creatinine < 1.8 mg/dL or creatinine clearance greater or equal than 40 cc/min
as defined by the Cockcroft-Gault Equation*. Males(mL/min):(140-age)* ABW(kg) / 72*
(serum creatinine(mg/dl)); Females (mL/min):0.85*(140-age)* ABW(kg) / 72*(serum
creatinine (mg/dl))

11. Women of childbearing potential should be advised to avoid becoming pregnant and
practice effective methods of contraception. Men should be advised not to father a
child while receiving treatment with azacitidine. Azacitidine is classified as
Pregnancy Category D. Females of childbearing potential: Recommendation is for 2
effective contraceptive methods during the study. Adequate forms of contraception are
double-barrier methods (condoms with spermicidal jelly or foam and diaphragm with
spermicidal jelly or foam), oral, depo provera, or injectable contraceptives,
intrauterine devices, and tubal ligation. Male patients with female partners who are
of childbearing potential: Recommendation is for male and partner to use at least 2
effective contraceptive methods, as described above, during the study.

12. Women of childbearing potential should have a pregnancy test within 7 days before
initiation of study drug.

Exclusion Criteria:

1. Patients receiving any other investigational agents.

2. Patients who are pregnant or breast-feeding.

3. Patients with clinically significant heart disease (NYHA Class III or IV).

4. Known or suspected hypersensitivity to azacitidine or mannitol.

5. Patients with advanced malignant hepatic tumors.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) of Azacitidine

Outcome Description:

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.

Outcome Time Frame:

First 28 day cycle

Safety Issue:


Principal Investigator

Jorge Cortes, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

August 2012

Completion Date:

Related Keywords:

  • Leukemia
  • Leukemia
  • Chronic Myeloid Leukemia
  • CML
  • Complete cytogenetic remission
  • CCyR
  • Minimal residual disease
  • Philadelphia chromosome (Ph)-
  • BCR/ABL-positive
  • Tyrosine kinase inhibitor
  • TKI
  • Azacitidine
  • 5-Azacytidine
  • 5-AZA
  • Vidaza
  • 5-AZC
  • AZA-CR
  • Ladakamycin
  • NSC-102816
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Neoplasm, Residual



UT MD Anderson Cancer Center Houston, Texas  77030