Acute Promyelocytic Leukemia (APL) Treated With ATRA, Arsenic Trioxide and Gemtuzumab Ozogamicin

Condition(s) targeted: Leukemia

Intervention: ATRA (Drug); ATO (Drug); GO (Gemtuzumab ozogamicin) (Drug); Methylprednisolone (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

The goal of this clinical research study is to learn if the combination of all-trans retinoic acid (ATRA), arsenic trioxide (ATO), and gemtuzumab ozogamicin (GO) can help to control APL. The safety of this drug combination will also be studied.

Official title: Phase II Study of Treatment of Acute Promyelocytic Leukemia (APL) With ATRA, Arsenic Trioxide and Gemtuzumab Ozogamicin (GO)

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Event Free Survival (EFS)

Detailed description: Study Drugs: ATRA and ATO are designed to cause the APL cells to mature and function normally. ATO also kills leukemia cells directly. GO is designed to attach to CD33, a certain protein that is often found in leukemia cells, causing them to die. Study Drug Administration: Induction: If you are found to be eligible to take part in this study, you will begin Induction. This is called Course 1. During Induction, you will take ATRA by mouth 2 times a day, starting on Day 1. You will also receive ATO through a needle in your vein every day, starting on Day 1. You will continue receiving the drugs until your bone marrow no longer shows APL cells. This is called complete remission (CR). Some time during Weeks 1-4, you may be given GO one time by vein, over about 2 hours. You will receive methylprednisolone by mouth or by vein once a day for 5 days to help prevent side effects. If by vein, the infusion will take about 30 minutes. If you stop taking either ATRA or ATO because of side effects, you may continue to receive GO every 4 to 5 weeks until you have been in complete remission for 28 weeks. Consolidation: Within 1 week after the disease is in CR, the consolidation treatment will begin. You will receive ATO by vein for 5 days total during Weeks 1-4 of Courses 2-5. Each course is about 8 weeks. You will take ATRA by mouth twice a day during Weeks 1-2 and 5-6 of Courses 2-5. If your study doctor thinks it is needed, you may receive GO by vein over about 1 hour. You will receive 2 doses about 5 weeks apart. Your doctor may change your dose or schedule if it is in your best interest. If your study doctor agrees, you may have the consolidation treatment given by your home doctor. Your home doctor will be contacted by the research staff and will be provided with the treatment details. Your home doctor will be asked to perform the physical exam and blood work at his/her office, and will be asked to send laboratory reports back to the research nurse. You will be asked to return to MD Anderson every 3 months for follow-up visits. Study Visits: Before each course of treatment, you will have a physical exam. At each visit, you will be asked about any side effects you may be having and any drugs you may be taking. On Days 1-7 of Course 1, blood (about 1 tablespoon) will be drawn for routine tests. Blood will then be drawn 2 times a week until the disease is in CR. If you are able to become pregnant, you will have a blood (about ½ teaspoon) or urine pregnancy test within 48 hours before taking the first dose of GO. To take part in this study, you cannot be pregnant. You will have a bone marrow aspirate collected on Day 21-28 of Course 1 to check the status of your disease. If your doctor thinks it is needed, you may have a bone marrow aspirate collected every 7-10 days until your blood cell counts return to a certain level. Once the disease is in CR, blood (about 1 tablespoon) will be drawn before you receive every round of ATO and every round of GO, and at least every week during Weeks 1-4 of Courses 2-5. You will have an ECG before you receive ATO during Weeks 1-4 of Courses 1-5. Length of Study: You may continue taking the study drugs for up to 4 consolidation courses. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, you do not respond to the study drugs, or if you are unable to follow study directions. Your participation on the study will be over once you have completed the long-term follow up. End-of-Treatment Visit: You will have an end of treatment visit within 1 month (+/- 1 week) after the last dose of any study drug. The following procedures will be performed:

- You will have a physical exam.

- You will be asked about any side effects you may be having and any drugs you may be

taking.

- Blood (about 1 tablespoon) will be drawn for routine tests.

Follow-up Visits: At about 12, 18, and 24 months after your last treatment:

- You will have a physical exam.

- Blood (about 1 teaspoon) will be drawn for routine tests.

- You will have a bone marrow aspiration to check the status of the disease.

- You will be asked about any side effects you may be having and any drugs you may be

taking. Long-Term Follow-up Visits: You will be contacted every 6-12 months by telephone call, regular mail, or e-mail to check the status of the disease. If contacted by phone, the call should last about 10 minutes. This is an investigational study. ATRA and ATO are FDA approved and commercially available. GO is not FDA approved or commercially available. At this time, it is being used for research purposes only. Up to 100 patients will take part in the study. All will be enrolled at MD Anderson.

Minimum age: 10 Years. 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 by cytogenetics, PCR, or POD test. 2. Ability to understand and the willingness to sign a written informed consent document indicating that they are aware of the investigational nature of the study. 3. Patients in whom therapy for APL was initiated on an emergent basis are eligible (patients may have already started treatment with ATRA, ATO, and/or one dose of idarubicin due to the urgency to start therapy early). 4. Patients age 10 years and older are eligible. 5. Women of child-bearing potential must have a negative serum pregnancy test at screening. In addition to having a negative pregnancy test confirmed at screening, all female participants of childbearing potential must have a negative pregnancy test confirmed within 48 hours prior to dosing with the study drug. 6. All sexually active subjects (males and females of child-bearing potential) agree to use 2 effective methods of contraception for the duration of the study. Exclusion Criteria: 1. QTcF interval on the EKG greater than 480 milliseconds. 2. Patients with creatinine > 2. 5 and total bilirubin >/= 2. 0 and ALT/AST > 3 times upper limit of normal unless felt to be related the underlying leukemia by the treating physician or hemolysis or Gilbert's disease.

Farhad Ravandi-Kashani, MD, Phone: 713-745-0394

University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States; Recruiting

University of Texas MD Anderson Cancer Center Website

Starting date: October 2011
Last updated: June 4, 2015