DB-67 in Myelodysplastic Syndrome (MDS)

• Response Rate [ Time Frame: 4 cycles (approximately 16 weeks) ] [ Designated as safety issue: No ]
• Toxicity Rate [ Time Frame: 4 cycles (approximately 16 weeks) ] [ Designated as safety issue: Yes ]

The goal of this clinical research study is to learn if AR-67 can help to control Myelodysplastic Syndrome (MDS).

Primary Objective:

1. Evaluate the response rate of AR-67 in MDS.

Secondary Objective:

1. Evaluate the safety of AR-67 in patients with MDS.
2. Evaluate the survival and disease-free survival of patients with MDS treated with AR-67.
3. Evaluate the response duration of patients with MDS treated with AR-67.

The Study Drug:

AR-67 is designed to block the function of an important protein (topoisomerase I) in cancer cells that helps repair damage to DNA (the genetic material of cells). When this protein is blocked, cancer cells may die.

Study Drug Administration:

If you are found to be eligible to take part in this study, on Days 1-5 of each 28-day study "cycle", you will receive AR-67 through a needle into the vein or a central venous catheter (CVC) into your vein over about 1 hour. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this procedure to you in more detail, and you will be required to sign a separate consent form for this procedure.

On Days 6-28 of each cycle, you will receive no study drug.

If your doctor thinks it is needed, your study cycles may be shortened so that you will receive the study drug more often.

Study Visits:

Before the start of each cycle, you will have a physical exam and your medical history will be recorded.

Once or twice every week of Cycle 1 and then every 2-4 weeks after that, blood (about 2 tablespoons each time) will be drawn for routine tests.

At the end of Cycle 1, and then once every 1-3 cycles, you will have a bone marrow aspirate and/or biopsy to check the status of the disease.

If you take the study drug for more than 12 months, you will have bone marrow aspirates and biopsies every 6-12 months. They may be performed more often if the study doctor thinks it is needed.

Length of Study:

You may continue taking the study drug for as long as you are benefitting. You will be taken off study if the disease gets worse or you experience intolerable side effects.

This is an investigational study. AR-67 is not FDA approved or commercially available. At this time, AR-67 is only being used in research.

Up to 25 participants will take part in this study. All will be enrolled at M. D. Anderson.

Inclusion Criteria:

1. Patients with either of the following diagnoses: a. MDS and > 5% blasts, or IPSS risk group intermediate-1, intermediate-2 or high risk; b. chronic myelomonocytic leukemia (CMML)
2. Patients must have failed prior therapy with either a hypomethylating agent (eg, azacytidine, decitabine) alone or in combination with other agents. Patients with abnormalities in chromosome 5q, should have failed either a hypomethylating agent or lenalidomide. Patients intolerant or unable to receive these agents will be considered eligible.
3. Age >/= 18 years. Because no dosing or adverse event data are currently available on the use of AR-67 in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.
4. ECOG performance status 0-2.
5. Patients must have normal organ function as defined below: a. Total bilirubin: </= 1.5 x institutional upper limit of normal; b. ALT(SGPT): </= 2.5 x institutional upper limit of normal; c. Creatinine: </= 1.5 x institutional upper limit of normal.
6. The effects of AR-67 on the developing human fetus at the recommended therapeutic dose are unknown. For this reason women of child-bearing potential (ie, not post-menopausal for at least 12 months and not surgically sterile) and men must agree to use effective methods of contraception. Women of childbearing potential (any women who is not surgically sterile or > 2 years post menopause) must give consent for using a reliable method of contraception (eg, double-barrier, tubal ligation or stable hormonal contraception) throughout the duration of study participation.
7. **continued from above: Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
8. Ability to understand and the willingness to sign a written informed consent document.
9. Patients must have been off chemotherapy for 2 weeks prior to entering this study unless there is evidence of rapidly progressive disease. Patients must have recovered from the toxic effects of prior therapy to grade </= 1. The use of hydroxyurea is allowed to control counts up to 24 hrs prior to the start of therapy with AR-67.

Exclusion Criteria:

1. Nursing and pregnant females or females who plan pregnancy during the duration of the study.
2. Active and uncontrolled systemic infections.
3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.