Phase I-II Study of Idarubicin, Cytarabine, and Sorafenib (BAY43-9006)

Acute Myeloid Leukemia Clinical Trial

Official title: Phase I-II Study of Idarubicin, Cytarabine, and Sorafenib (BAY43-9006), an Oral Vascular Endothelial Growth Factor (VEGF), Rapidly Accelerated Fibrosarcoma (RAF) and FMS-like Tyrosine Kinase 3 (FLT3), in Patients With High-risk MDS and AML

Status Completed

Clinical Trial Summary

A primary goal of this clinical research study is to find the highest safe dose of sorafenib that can be given in combination with idarubicin and Ara-C for the treatment of acute myelogenous leukemia (AML) and high-risk, myelodysplastic syndrome (MDS).

Once the highest safe dose is found, researchers will then try to learn if this combination treatment can help control AML and high-risk MDS in newly diagnosed patients. The safety of this treatment combination will also be studied.

Clinical Trial Description

The Study Drugs:

Sorafenib is designed to block the function of important proteins in cancer cells. When active, these proteins help cause abnormal growth and behavior of leukemia cells.

Idarubicin and Ara-C are both designed to insert themselves into DNA (the genetic material of cells) and to stop DNA from repairing itself.

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study.

If you are enrolled in the Phase I part of this study, the dose of sorafenib you receive with Ara-C and idarubicin will depend on when you enrolled in this study. Each new group of 3 participants will receive a higher dose level of sorafenib than the previous group until the highest safe dose of sorafenib that can be given in combination with Ara-C and idarubicin is reached.

If you are enrolled in the Phase II portion of this study, you will receive the highest safe dose of sorafenib in combination with Ara-C and idarubicin found in the Phase I part.

Study Drug Administration:

During the study, you will receive treatment over 28-day "cycles." The doses of idarubicin and Ara-C are the same for all study participants.

On Days 1-4 (Days 1-3 if you are older than 60) of each induction cycle (#1 and possibly #2), you will receive Ara-C through a nonstop infusion (through a needle in your vein). You will also receive steroids by mouth or through a vein every day to reduce the risks of side effects, such as rash.

On Days 1-3 of each induction cycle (#1 and possibly #2), you will receive idarubicin by vein over 1 hour once a day.

In general, sorafenib will be taken by mouth twice daily on Days 1-7, unless otherwise instructed. However, the dose of sorafenib may differ among study participants. Sorafenib should be taken with water on an empty stomach. Your study doctor will give you complete instructions on when and how to take sorafenib.

Depending on the side effects that you may have, the dose of sorafenib may be decreased, stopped until side effects go away, or even stopped completely, if your doctor thinks that this is in your best interest.

Study Visits:

During Cycles 1-2, you will have study visits about 2 times a week. You may need to have study visits more often when the study doctor thinks it is necessary. At these visits, you will have the following procedures performed.

• You will be asked about any side effects you may have experienced and any medications you may be taking.

• Blood (about 2 teaspoons) will be drawn for routine tests.

During Cycles 1 and 2, between Days 21-28, you will have a bone marrow aspirate and/or biopsy performed to check the status of the disease.

For Cycle 3 and in further cycles, you will have a bone marrow aspirate as determined necessary by your doctor. If your doctor thinks you have responded to the treatment, you will then have bone marrow aspirates collected every 3-6 months, if your doctor feels this to be necessary.

Consolidation Therapy:

If it is found that the disease is responding to treatment, you may receive 5 additional cycles of therapy. These cycles are called "consolidation" therapy and will be given every 4-6 weeks.

On Days 1-3, Ara-C will be given as a nonstop infusion. You will also receive steroids either by mouth or by vein to help reduce the risk of side effects.

On Days 1-2, idarubicin will be given by vein over 1 hour.

Sorafenib will be taken twice daily by mouth for 7 or more days, at a schedule determined by your study doctor.

After each cycle, about every 4-6 weeks, blood (about 2 teaspoons) will be drawn to check your blood count levels.

Maintenance Therapy:

After 5 cycles of consolidation therapy, and according to your response to consolidation therapy, you may continue on this study to receive "maintenance" treatment, as needed, and as determined by your study doctor for up to 7 more cycles.

You will take sorafenib twice a day every day during the 28-day cycle.

Every 1-4 weeks, blood (about 2 teaspoons) will be drawn for routine tests.

Length of Study:

You may receive up to 14 cycles in total of therapy. You may be taken off this study if the leukemia gets worse, develop another illness that interferes with taking the study drugs, or you have intolerable side effects.

This is an investigational study. Sorafenib is FDA approved and commercially available for the treatment of metastatic renal cancer only. Idarubicin is FDA approved for use in combination with other approved antileukemic drugs for the treatment of acute myeloid leukemia (AML) in adults. Cytarabine is FDA approved for use in the treatment of leukemia. The use of sorafenib combined with idarubicin and Ara-C in the treatment of AML and high-risk MDS is investigational and authorized for use in research only. Up to 75 patients will take part in this study. All patients will be enrolled at M. D. Anderson Cancer Center. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• AML
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Disorders

• NCT number: NCT00542971
• Study type: Interventional
• Source: M.D. Anderson Cancer Center
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 2007
• Completion date: May 2011