Official Title: “Treatment of APL With All-Trans Retinoic Acid, and Arsenic +/- Gemtuzumab and Theophylline”

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 APL. Researchers also want to learn if theophylline can help to control APL.

Study Type: Interventional

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

Study Primary Completion Date: September 2008

All-trans retinoic acid (ATRA) and ATO are designed to cause the APL cells to mature and function normally. Gemtuzumab ozogamicin (GO) is designed to kill APL cells. Theophylline is designed to increase the effectiveness of ATRA and ATO.

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. 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bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.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 and theophylline by mouth on Day 1. You will continue to receive theophylline by mouth every day that you receive either ATRA or ATO. You and your treating physician may choose not to include theophylline as a part of your treatment.

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 to check the levels of theophylline in the blood and 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 began the study with a lower white blood cell count, you will have follow-up visits every 3 months for the first 6 months, and then every 6 months for the 18 months after that.

At these visits, blood (about 1 tablespoon) will be drawn for routine tests and you will have a bone marrow aspirate.

If you had a 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 and theophylline are both FDA approved and commercially available. Their use in APL patients is investigational. Up to 50 patients will take part in the study. All will be enrolled at M. D. Anderson.

Intervention(s) in this Clinical Trial

• Drug: All-Trans Retinoic Acid
  • All-Trans Retinoic Acid 45 mg/m2 daily
• Drug: Arsenic Trioxide
  • Arsenic Trioxide 0.15mg/kg daily
• Drug: Gemtuzumab Ozogamicin
  • Gemtuzumab Ozogamicin 9 mg/m2 day 1
• Drug: Theophylline
  • Theophylline 100mg days 1-3 200mg days 4-6 300mg days thereafter

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • All-Trans Retinoic Acid + Arsenic Trioxide
• Experimental: 2
  • All-Trans Retinoic Acid + Arsenic Trioxide + Gemtuzumab Ozogamicin + Theophylline

Primary Measures

• Assess if the following will improve CR rate w/o increasing toxicity in high-risk untreated APL: arsenic trioxide D1, rather than D10, of therapy, + theophylline, and administration of gemtuzumab ozogamicin if WBC rises to > 30,000 after treatment star
  • Time Frame: 3/2009
    Safety Issue?: No

Inclusion Criteria:

• 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).
• Provision of written informed consent.

Exclusion Criteria:

• Cannot be in first trimester of pregnancy (ATRA is teratogenic)
• QTC interval must not be greater than 480 milliseconds.
• 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: M.D. Anderson Cancer Center

Overall Clinical Trial Officials and Contacts

Farhad Ravandi-Kashani, MD Principal Investigator M.D. Anderson Cancer Center  

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

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00413166

Study ID Number: 2006-0706

ClinicalTrials.gov Identifier: NCT00413166

Health Authority: United States: Institutional Review Board

(MD Anderson's website)