Decitabine for Older or Unfit Patients With Acute Myeloid Leukemia (AML)

Study Overview
=================
Brief Summary
-----------------
The goal of this clinical research study is to compare how well 2 different dosing schedules of decitabine may help control AML. Decitabine is designed to damage the DNA (the genetic material) of cells, which may cause cancer cells to die.

Detailed Description
-----------------
Study Groups: If you are found to be eligible to take part in this study, you will be assigned to 1 of 2 dose levels of decitabine based on when you join this study. If you are among the first 20 participants, you will have an equal chance of being in either group. If you enroll after that, you will have an increasingly higher chance (51-100%) of being assigned to the group that had better results, depending on how much better that treatment arm is. Study Drug Administration: Each cycle is about 4-8 weeks, depending on the doctor's decision. In this study you will receive induction therapy to try to control the disease and cause remission (this is when tests and/or the doctor cannot find signs of the disease). If you are in Group 1, you will receive decitabine by vein over about 1 hour for 5 days. If you are in Group 2, you will receive decitabine by vein over about 1 hour for 10 days. If the disease is in remission, you may receive more cycles (called maintenance) to help keep the disease under control. If you are in Group 2, you will receive 5 day dosing during maintenance, or when the doctor thinks it is in your best interest. Your dose schedule or dose level may be changed if the doctor feels it is in your best interest. Study Visits: The following tests and procedures will be performed: Blood (about 2-3 teaspoons) will be drawn 1-2 times weekly for first cycle, then every 2-4 weeks after that. After the 6th cycle or sooner if the doctor decides, this blood draw will be performed only 1 time per cycle. Every 1-3 cycles, you will have a bone marrow aspiration/biopsy to check the status of the disease. Blood (about 2-3 teaspoons) may also be drawn for genetic testing if the disease is in remission and the doctor thinks it is needed. Length of Treatment: You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions. Your participation in this study will be over after the follow-up phone calls. Follow-Up: After you stop the study treatment, you will be called by phone twice a year and asked how you are feeling. The phone calls should last about 5 minutes each time. This is an investigational study. Decitabine is FDA approved and commercially available for the treatment of myelodysplastic syndrome (MDS). Its use to treat AML is investigational. Up to 100 participants will be enrolled in this study. All will take part at MD Anderson.

Official Title
-----------------
A Randomized Phase II Study of Two Schedules of Decitabine for Frontline Therapy of Older or Unfit Patients With Acute Myeloid Leukemia (AML)

Conditions
-----------------
Leukemia

Intervention / Treatment
-----------------
* Drug: Decitabine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with previously untreated AML (by the World Health Organization (WHO) criteria, i.e. >/= 20% blasts) Prior biologic therapies (such as growth factors) and targeted therapies administered for the treatment of prior myelodysplastic syndrome are allowed, with the exception of hypomethylating agents 5-azacytidine or decitabine. Patients must have been off such therapy for 1 week prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease. Hydroxyurea, and a single dose of cytarabine up to 3 g/m2, is permitted for control of counts prior to treatment. Patients >/= 60 are eligible if not a candidate for standard cytarabine plus anthracycline chemotherapy as determined by Kantarjian's score (Appendix D) Patients younger than 60 may also be included if felt not to be a candidate for intensive anthracycline plus cytarabine based chemotherapy. Performance 0-3 (ECOG). Adequate liver function (Total bilirubin of < 2 mg/dl) unless due to hemolysis, leukemia organ infiltration or Gilbert's syndrome and renal function (creatinine < 2.5 mg/dl). Signed informed consent Exclusion Criteria: Nursing and pregnant females. Female patients of childbearing potential and male patients should practice effective methods of contraception such as double barrier method. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Negative urine pregnancy test (women of childbearing potential) Active and uncontrolled infections. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, active significant other cancers requiring chemotherapy and/or radiation therapy within past 6 months (excluding non-melanoma skin cancer) or psychiatric illness/social situations that would limit compliance with study requirements.

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Decitabine - 5 Day Regimen<br>Decitabine 20 mg/m2 by vein daily for 5 days. | Drug: Decitabine<br>* 20 mg/m2 by vein daily for either 5 or 10 days.<br>* Other names: Dacogen;|
| Experimental: Decitabine - 10 Day Regimen<br>Decitabine 20 mg/m2 by vein daily for 10 days. | Drug: Decitabine<br>* 20 mg/m2 by vein daily for either 5 or 10 days.<br>* Other names: Dacogen;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With a Response | Response is defined as Complete Response (CR) + Partial Remission (PR) + Complete Remission with incomplete recovery (CRi) + Clinical Benefit. CR is the normalization of the peripheral blood and bone marrow with </= 5% bone marrow blasts, a peripheral blood granulocyte count >/= (1.0 x 10^9/L, and a platelet count >/= 100 x 10^9/L). PR is the same as CR except for the presence of 6-15% marrow blasts, or 50% reduction if <15% at start of treatment. CRi meets all criteria for CR except for platelet recovery to >100 x 10^9/L and/or granulocyte count > (1.0 x 10^9/L). Clinical benefit is platelets increase by 50% and to above 30 x 10^9/L untransfused (if lower than that pretherapy); or granulocytes increase by 100% and to above 10^9/L (if lower than that pre-therapy); or hemoglobin increase by 2 g/dl; or transfusion independent; or splenomegaly reduction by > 50%; or monocytosis reduction by > 50% if pretreatment > 5 x 109/L. | Up to 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Time from date of treatment start until date of death due to any cause or last Follow-up. | Up to 5 years | 
| Response Duration | The date of response to date of loss of response or last follow-up. Response is defined as Complete Response (CR) + Partial Remission (PR) + Complete Remission with incomplete recovery (CRi) + Clinical Benefit. CR is the normalization of the peripheral blood and bone marrow with </= 5% bone marrow blasts, a peripheral blood granulocyte count >/= (1.0 x 10^9/L, and a platelet count >/= 100 x 10^9/L). PR is the same as CR except for the presence of 6-15% marrow blasts, or 50% reduction if <15% at start of treatment. CRi meets all criteria for CR except for platelet recovery to >100 x 10^9/L and/or granulocyte count > (1.0 x 10^9/L). Clinical benefit is platelets increase by 50% and to above 30 x 10^9/L untransfused (if lower than that pretherapy); or granulocytes increase by 100% and to above 10^9/L (if lower than that pre-therapy); or hemoglobin increase by 2 g/dl; or transfusion independent; or splenomegaly reduction by > 50%; or monocytosis reduction by > 50% if pretreatment | Up to 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AML, Leukemia, Acute myeloid leukemia, Response rates, Decitabine, Dacogen