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An Open-Label, Phase I/II Study of Two Different Schedules of Dasatinib (Sprycel) and Decitabine (Dacogen) Used in Combination for Patients With Accelerated or Blastic Phase Chronic Myelogenous Leukemia (Protocol CA180357)

Phase 1/Phase 2
18 Years
Open (Enrolling)

Thank you

Trial Information

An Open-Label, Phase I/II Study of Two Different Schedules of Dasatinib (Sprycel) and Decitabine (Dacogen) Used in Combination for Patients With Accelerated or Blastic Phase Chronic Myelogenous Leukemia (Protocol CA180357)

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study
group and dose level based on when you join this study and the side effects that are seen.
Your doctor will discuss this with you in more detail.

There will be up to 5 doses of dasatinib tested in Phase 1. The first 3 participants will
receive a lower dose of therapy. If no major side effects are seen in these participants,
the next participants will receive a higher dose. Once a dose is identified that is
well-tolerated for most participants, that dose will be used for all new participants. If
you are in Phase 2, you will receive a dose level tested in Phase 1.

You will receive one of 2 doses of decitabine. What dose you receive is determined by
chance (like a coin toss).

Study Administration:

Each cycle is 28 days.

You will take dasatinib by mouth 1 time a day.

You will receive decitabine by vein for 10 days of each cycle. If the doctor thinks it is in
your best interest, you may receive decitabine for fewer days each cycle (5 days instead of
10 days). Your doctor will decide how many doses you will take based on side effects you may
have and the status of the disease.

If you have severe side effects from the study drug, the study doctor may decide to stop
drug dosing until your side effects improve.

You will be asked to keep a study diary that will be reviewed at scheduled study visits. In
the diary, you will record when you take the study drug.

Study Visits:

At every visit, you will be asked about any side effects you may have had and to list any
drugs you may be taking.

Every week for the first 3 cycles and then every 2-4 weeks after that, blood (about 1
tablespoon) will be drawn to check your blood cell counts.

About 1 week after your first dose, you will have an ECG.

Every 1-2 weeks for the first 3 cycles and then every 4-8 weeks after that, blood (about 1
tablespoon) will be drawn to test your kidney and liver function.

Before the start of Cycle 2, every 2-4 cycles after that for the first year, and then every
6 cycles after that, you will have a complete physical exam.

Before the start of Cycle 2, every 3 cycles after that during the first year, then every 4-6
cycles (as needed) you will have a bone marrow aspirate to check the status of the disease.

After Cycle 6, the number of blood draws and bone marrow collections may be changed.

Length of Study:

You may continue taking the study drugs 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.

This is an investigational study. Dasatinib is FDA approved and commercially available for
the treatment of patients with certain types of CML.

Decitabine is FDA approved for the treatment of patients with myelodysplastic syndrome.

The combination of these drugs to treat CML is investigational.

Up to 84 patients will take part in this study. All will be enrolled at MD Anderson.

Inclusion Criteria:

1. Patients age 18 years of age or older with CML-AP, CML-BP or Philadelphia
chromosome-positive acute myeloid leukemia defined as follows: CML-AP is defined by
the presence of 15-29% blasts in peripheral blood (PB) or bone marrow (BM), >/= 20%
basophils in PB or BM, >/= 30% blasts plus promyelocytes (with blasts <30%) in PB or
BM, <100 x10(9)/L platelets unrelated to therapy, or by clonal cytogenetics evolution
(i.e., the presence of cytogenetic abnormalities other than the Philadelphia
chromosome); CML-BP is defined by the presence of >/= 30% blasts in the bone marrow
and/or peripheral blood or the presence of extramedullary disease.

2. Patients are eligible whether they have received or not prior TKI therapy. For the
phase I portion of the study, patients who had received prior therapy with dasatinib
should have been able to tolerate the dose equivalent to the starting dose of
dasatinib in the dose level at which the patient is being entered. Patients who
previously received dasatinib but never at the dose being proposed are eligible
provided they tolerated the maximum dose they were prescribed with no grade 3-4
toxicity not responding to optimal management.

3. ECOG performance status 0-3.

4. Men and women of childbearing potential should practice effective methods of
contraception. Men and women of childbearing potential are defined as: a male that
has not been surgically sterilized or a female that has not been amenorrheic for at
least 12 consecutive months or that has not been surgically sterilized. Patients must
use birth control during the study and for 3 months after the last dose of study drug
if they are sexually active.

5. Women of childbearing potential must have a pregnancy test at screening.

6. Signed informed consent.

7. Patients must have been off all prior therapy for CML for 2 weeks prior to start of
study therapy and recovered from the toxic effects of that therapy. Exceptions to
these are hydroxyurea and TKIs (including but not limited to imatinib, nilotinib, and
bosutinib) which should be discontinued >/= 24 hrs prior to the start of therapy.
Patients who are receiving dasatinib prior to enrollment do not have to discontinue
this agent prior to start of study therapy.

8. Adequate organ function: Serum creatinine /=60
mL/min; Total bilirubin hemolysis); Alanine aminotransferase (ALT) leukemic involvement.

Exclusion Criteria:

1. NYHA cardiac class 3-4 heart disease.

2. Cardiac disease including: Uncontrolled angina within 3 months. Diagnosed or
suspected congenital long QT syndrome; Any history of clinically significant
ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, or
Torsades de pointes); Prolonged QTc interval on pre-entry electrocardiogram (> 470
msec) on both the Fridericia and Bazett's correction; Uncontrolled hypertension
(defined for this protocol as sustained systolic BP >/=150 and diastolic >/=100);
Patients currently taking drugs that are generally accepted to have a risk of causing
Torsades de Pointes.

3. Serious uncontrolled medical disorder or uncontrolled active systemic infection or
current unstable or decompensated respiratory or cardiac conditions which makes it
undesirable or unsafe for the patient to participate in the study.

4. Patients with known, clinically significant pericardial or pleural effusion.

5. History of significant bleeding disorder unrelated to cancer, including diagnosed
congenital bleeding disorders (e.g., von Willebrand's disease), or diagnosed acquired
bleeding disorders within one year (e.g., acquired anti-factor VIII antibodies).

6. Subject is receiving potent inhibitors of CYP3A4; for such medications, a wash-out
period of >/= 7 days is required prior to starting dasatinib unless discontinuation
or substitution of such an inhibitor is not in the best interest of the patient as
determined by the investigator. These include the following medications:
itraconazole, ketoconazole, miconazole, voriconazole; amprenavir, atazanavir,
fosamprenavir, indinavir, nelfinavir, ritonavir; ciprofloxacin, clarithromycin,
diclofenac, doxycycline, enoxacin, isoniazid, ketamine, nefazodone, nicardipine,
propofol, quinidine, telithromycin. In instances where use of these agents is felt to
be required for the best management of the patients, inclusion of such a patients
should be discussed with PI and the rationale documented.

7. Females who are pregnant or are currently breastfeeding.

8. Patients that are eligible (including having available donor) and willing to receive
an allogeneic stem cell transplant within 4 weeks.

Type of Study:


Study Design:

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

Outcome Measure:

Maximum Tolerated Dose (MTD) Dasatinib and Decitabine

Outcome Description:

Maximum tolerated dose (MTD) defined as highest dose at which 0 of 3 or

Outcome Time Frame:

End of 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:

June 2012

Completion Date:

Related Keywords:

  • Leukemia
  • Leukemia
  • Chronic myelogenous leukemia
  • Chronic myeloid leukemia
  • CML
  • Accelerated phase
  • Blastic phase
  • Dasatinib
  • BMS-354825
  • Sprycel
  • Decitabine
  • Dacogen
  • Blast Crisis
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive



UT MD Anderson Cancer CenterHouston, Texas  77030