All-trans Retinoic Acid, and Arsenic +/- Gemtuzumab and Theophylline

Condition(s) targeted: Acute Promyelocytic Leukemia

Intervention: All-Trans Retinoic Acid (ATRA) (Drug); Arsenic Trioxide (ATO) (Drug); Gemtuzumab Ozogamicin (GO) (Drug); Theophylline (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: M.D. Anderson Cancer Center

Official(s) and/or principal investigator(s):
Farhad Ravandi-Kashani, MD, Principal Investigator, Affiliation: M.D. Anderson Cancer Center

Overall contact:
Farhad Ravandi-Kashani,, MD, Phone: 713-745-0394, Email: fravandi@mdanderson.org

The goal of this clinical research study is to learn if starting arsenic trioxide (ATO) therapy on Day 1 rather than Day 10 is more effective in treating patients with newly-diagnosed acute promyelocytic leukemia (APL).

Official title: Treatment of APL With All-trans Retinoic Acid, and Arsenic +/- Gemtuzumab and Theophylline

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome: Complete Response (CR) Rate

Detailed description: All-trans retinoic acid (ATRA) and ATO are designed to cause the APL cells to mature and function normally. Gemtuzumab ozogamycin (GO) is designed to kill APL cells.

Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. Blood (about 5 tablespoons) will be drawn for routine tests. This routine blood draw will include a pregnancy test for women who are able to have children (or you may have a urine pregnancy test). To be eligible to take part in this study, the pregnancy test must be negative. You will have a bone marrow aspirate to confirm the APL diagnosis. To collect a bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of

bone marrow is withdrawn through a large needle. You will have an electrocardiogram (ECG - -

a test that measures the electrical activity of the heart).

If you are found to be eligible to take part in this study, you will begin induction. During induction, you will receive ATRA, by mouth starting on Day 1. You will also receive ATO through a needle in your vein over 2 hours starting on Day 1. You will continue receiving the drugs every day until your bone marrow no longer shows APL cells.

If you had a high white blood cell count at screening, you will receive GO through a needle in your vein over 30 minutes on Day 1.

During induction, blood (about 1-3 tablespoons) will be drawn every day during Week 1, and then 2 times a week after that. This blood will be drawn for routine tests.

If you achieve a complete remission during the induction phase, you will continue to the maintenance phase. During the maintenance phase, you will receive ATO by vein over 2 hours Monday-Friday for 4 weeks. After the 4 weeks of receiving the study drug, you will have a 4-week period "off" (when no study drug is given). ATRA is given by mouth every day for 2 weeks. This 2 weeks is followed by 2 additional weeks when no study drug will be given. You will continue to take ATRA until treatment with ATO is complete.

During maintenance, blood (about 1-3 tablespoons) will be drawn before every 4-week cycle of ATO, and then every week for routine tests. You will also have an ECG before every 4 week cycle when you take ATO.

If you do not achieve a complete remission during induction you will be taken off study.

If at any point during the study your white blood cell count rises above 30,000, you will receive GO by vein over 30 minutes.

You will remain in the hospital for about the first 7 days of induction. After that, you must remain in Houston for the next 3-4 weeks. Once in the maintenance phase, you may be treated at home, but must return to M. D. Anderson for study visits.

After maintenance is complete, you will have follow-up visits for an additional 2 years. If at any time during the active study or follow-up the disease gets worse or intolerable side effects occur, you will be taken off the study.

If you had a low or high white blood cell count when you joined the study, you will have follow-up visits every 3 months for 2 years. At these visits, blood (about 1 tablespoon) will be drawn for routine tests and you will have a bone marrow aspirate.

This is an investigational study. ATRA and ATO are FDA approved and commercially available. However, their use in this study and in this combination is considered investigational. GO is also FDA approved and commercially available. Its use in APL patients is investigational. Up to 80 patients will take part in the study. All will be enrolled at M. D. Anderson.

Minimum age: N/A. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

1. A diagnosis of APL based on the presence of the PML-RAR alpha fusion gene. Documentation can be done either cytogenetically (the t (15;17) is found, as a consequence of the formation of the fusion gene) or molecularly (PCR test for t (15;17), or a positive "POD" test (12).

2. Provision of written informed consent.

Exclusion Criteria:

1. Cannot be in first trimester of pregnancy (ATRA is teratogenic)

2. QTC interval must not be greater than 480 milliseconds.

3. Taking any drugs known to prolong the QT interval. Any patient taking them who has a baseline heart rate of less than 60 beats per minute at rest would have an EKG to evaluate for QTc prolongation, if the QTc is above the limit of 480 msec then the

patient would be given an option to be evaluated by cardiology. - QTC interval must

not be greater than 480 milliseconds.

Farhad Ravandi-Kashani,, MD, Phone: 713-745-0394, Email: fravandi@mdanderson.org

The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting
Farhad Ravandi-Kashani, MD, Phone: 713-745-0394, Email: fravandi@mdanderson.org

MD Anderson's website

Starting date: September 2006
Ending date: March 2010
Last updated: September 9, 2009