A Combination of PKC412 and 5-Azacytidine for the Treatment of Patients With Refractory or Relapsed Acute Leukemia and Myelodysplastic Syndrome (MDS)
The Study Drugs:
PKC412 is designed to block certain receptors (FLT3-Kinase) on cancer cells that are
responsible for cancer growth. This may cause the cancer cells to die.
5-azacytidine is designed to cause changes to certain genes that are thought to participate
in causing leukemia. These changes are thought to silence these genes so they cannot
contribute any longer to sustain the growth of leukemia and MDS.
If you are found to be eligible to take part in this study, you will be assigned to a part
of the study based on when you join.
- If you are one of the first 6 participants, you will receive a pre-planned dose of the
study drugs. If 2 participants experience severe side effects, the rest of this group
will receive a lower dose.
- If you are not one of the first 6 participants, and fewer than 2 patients had severe
side effects in the first group, you will receive the drugs at a higher dose than the
first 6 participants.
Study Drug Administration:
You will receive 5-azacytidine by vein over about 30 minutes or through a needle under your
skin on Days 1-7 of each 28-day study cycle. Your doctor will decide if you will get the
drug by vein or under the skin. You will be required to return to MD Anderson for the
first 7 days of every cycle to receive 5-azacytidine.
On Days 8-21 of cycle 1, you will take PKC412 capsules by mouth 2 times a day. Starting
with Cycle 2, you will take PKC412 capsules by mouth every day. The research staff will
tell you how to take the study drug and you will also be given instructions.
If you have severe side effects from the study drug, the study doctor may decide to stop
drug dosing until your side effects improve.
At every visit, you will be asked about any side effects you have experienced and to list
any drugs you may be taking.
- At the start of Cycles 1-2 (+/- 4 days) and then every 2-3 cycles, you will have a
complete physical exam.
- Every week during Cycles 1-3 (+/- 4 days) and then every 2-4 weeks, blood (about 1
tablespoon) will be drawn for routine tests and to test your kidney and liver function.
- On Day 28 of Cycle 1 (+/- 4 days) and then every 1-3 cycles, you will have a bone
marrow aspirate to check the status of the disease.
- On Day 8 (+/- 1 day) of each cycle for the first cycle before initiation of
Midostaurin, then before the start of Midostaurin on Cycle 2, then on Day 1 every 2-3
Cycles, you will have an ECG.
- On Days 8, 15, and 21 of Cycle 1 and Day 1 of Cycle 2, blood (about 1 teaspoon) will be
drawn for PK testing before you take the study drug.
If you stay on study for longer than 6 months, your doctor will decide what tests and
procedures you will have and when they will be performed. At least every 6-12 months you
will have a bone marrow aspirate.
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 or
intolerable side effects occur.
This is an investigational study. PKC412 is not FDA approved or commercially available. It
is currently being used for research purposes only. 5-azacytidine is FDA approved and
commercially available for the treatment of patients with MDS. The combination of these
drugs to treat refractory or relapsed acute leukemia and MDS is investigational.
Up to 54 patients will take part in this study. All will be enrolled at MD Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Patients with Complete Response (CR)
Jorge Cortes, MD
UT MD Anderson Cancer Center
United States: Food and Drug Administration
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