Clinical trial NCT01202877
Conditions: Leukemia
Keywords: Myelodysplastic Syndrome MDS Refractory acute leukemias Relapsed acute leukemia Acute myeloid leukemia AML 5-Azacytidine Azacitidine 5-aza Vidaza 5-AZC AZA-CR Ladakamycin NSC-102816 PKC412
Sponsor: M.D. Anderson Cancer Center
Start date: 2011-03-01; Completion date: 2015-07-01
Enrollment: 54 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of this clinical research study is to learn if the combination of PKC412 (also called Midostaurin) and 5-azacytidine can help to control refractory or relapsed acute leukemia and MDS. The safety and best dose of the combination of the drugs will also be studied.

Detailed description:
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.

Study Groups:

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.

Study Visits:

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 Pharmacokinetic (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.

Arms: arm 1: 5-azacytidine 75 mg/m2/d subcutaneously (SQ) or by vein (IV) on days 1-7 of a 28 day cycle. PKC412 50 mg by mouth twice daily for 14 days (days 8-21), of every 28 day cycle. Starting with cycle 2, PKC412 administered continuously (daily).
Interventions: intervention 1: 5-azacytidine intervention 2: PKC412
Intervention descriptions: intervention 1: Starting dose: 75 mg/m2/d subcutaneously (SQ) or by vein (IV) on days 1-7 of a 28 day cycle. intervention 2: Starting dose: 50 mg by mouth twice daily for 14 days (days 8-21), of every 28 day cycle. Starting with cycle 2, PKC412 administered continuously (daily).

Protocol documents: