AML, Leukemia, MDS
Conditions
Keywords
Leukemia, Acute myelogenous leukemia, AML, Myelodysplastic syndrome, MDS, Remission, Allogeneic stem cell transplant, Allotx, Azacitidine, 5-Azacitidine, 5-aza, Vidaza, 5-AZC, AZA-CR, Ladakamycin, NSC-102816
Brief summary
The goal of this clinical research study is to learn if Vidaza (azacitidine) will help to control the disease in patients with AML, CMML, or MDS after an allogeneic (donor) stem cell transplant. The safety of this drug will also be studied.
Detailed description
The Study Drug: Azacitidine is designed to block certain genes in cancer cells whose job is to stop the function of the tumor-fighting genes. By blocking the bad genes, the tumor-fighting genes may be able to work better. Study Groups: If you are found to be eligible to take part in this study, you will be randomly assigned (as in a flip of a coin) to 1 of 2 groups. * If you are in Group 1, you will receive azacitidine. * If you are in Group 2, you will not receive azacitidine. Study Drug Administration: If you are in Group 1, you will receive azacitidine through a needle under your skin on Days 1-5 of each cycle. Each cycle is 28 days long. Your dose of azacitidine may be lowered or stopped if certain side effects develop. Study Visits: About 2 or 3 days before each cycle and, if your doctor thinks it is needed, on Day 3 of each cycle and 1 time during Weeks 2 and 3 of each cycle, blood (about 4 teaspoons each time) will be drawn for routine tests. At 3, 6, and 12 months after the stem cell transplant: * You will have a complete medical history and physical exam. * Blood (about 4 teaspoons each time) will be drawn for routine tests. * You will have a bone marrow aspiration to check the status of the disease. You may come back for study visits more often if the doctor thinks it is needed. While on study, you will need to stay in Houston for about 3 months after the transplant (this is standard after stem cell transplants). Length of Study: You will be on study treatment for up to 1 year (up to 12 cycles of azacitidine). You will be taken off study early if you experience intolerable side effects or the disease gets worse. End-of-Treatment Visit: After you complete the planned treatment with azacitidine, you will have an end-of-treatment visit: * You will have a complete medical history and physical exam. * Blood (about 4 teaspoons) will be drawn for routine tests. * You will have a bone marrow aspiration to check the status of the disease. This is an investigational study. Azacitidine is FDA approved and is commercially available for the treatment of myelodysplastic syndrome. Up to 246 patients will take part in this study. All will be enrolled at MD Anderson.
Interventions
DRUGAzacitidine
32 mg/m\^2 given through a needle under the skin for five consecutive days of each 28 day cycle and the maximum treatment will be 12 cycles.
Sponsors
Celgene
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with a diagnosis of AML (World Health Organization classification: \>=20% blasts in the bone marrow and / or peripheral blood) or MDS (International Prognostic Scoring System intermediate-1 or higher) that at the time of allogeneic transplantation were in: - Induction Failure, relapsed disease or second or greater remission; patients in first complete remission that required more than 1 cycle of treatment to achieve the remission, or that have AML evolving from MDS, or that had the following abnormalities: FLT3 mutation, deletion of chromosome 5 or 7, MLL gene rearrangement, or more than or equal to 3 cytogenetics abnormalities. Patients with de novo or therapy-related MDS, CMML, or AML are also eligible, regardless of cytogenetics or molecular rearrangements. 2. Biphenotypic Leukemia that at the time of allogeneic transplantation was in induction failure, relapsed disease, first, second or greater remission. 3. Patients must be in complete remission post transplant. 4. Patient may be enrolled 40 to 100 days after transplant. 5. Age 18 to 75 years old. 6. Serum creatinine \< 1.8 mg/dL or creatinine clearance greater or equal than 40 cc/min as defined by the Cockcroft-Gault Equation\*. a. Males(mL/min):(140-age)\*IBW(kg) / 72\*(serum creatinine(mg/dl)) b. Females(mL/min):0.85\*(140-age)\*IBW(kg) / 72\*(serum creatinine(mg/dl)). 7. Serum direct bilirubin \< 1.5 mg/dL (unless Gilbert's syndrome). 8. SGPT \</= 200 IU/ml unless related to patient's malignancy. 9. Be able to understand and sign informed consent.
Exclusion criteria
1. Active uncontrolled infection. 2. Presence of uncontrolled graft-versus-host disease. 3. Patients that underwent allogeneic transplantation as a treatment of graft failure. 4. Pregnancy or breast-feeding (women of childbearing potential, any female who has experienced menarche and who has not undergone surgical sterilization or is not post-menopausal with a positive serum pregnancy test. 5. Known or suspected hypersensitivity to azacitidine or mannitol. 6. Patients with advanced malignant hepatic tumors.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse-free Survival (RFS) | 3 years | The time that a participant survives without relapse of the disease. |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) | 3 years |
Countries
United States
Participant flow
Recruitment details
Recruitment was from September 2009 to April 2017 for high risk subjects with acute myelogenous leukemia (AML) and myelodysplastic (MDS) patients who have undergone an allogeneic transplant.
Pre-assignment details
Patients were randomized to receive azacitidine (AZA) or standard of care 40 to 100 days after allo SCT.
Participants by arm
| Arm | Count |
|---|---|
| AZA Group Subjects randomized to the AZA treatment will receive 32 mg/m2 for 5 consecutive days of each 28 day cycle and the maximum treatment will be 12 cycles. Each cycle will consist of approximately 28 days, allowing the possibility that treatment within a cycle may be delayed for up to 4 weeks due to organ toxicity or hematologic toxicity. | 87 |
| Standard of Care Group Best standard of care (ie, no maintenance) | 94 |
| Total | 181 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Didn't meet eligibility to start cycle 1 | 4 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | AZA Group | Standard of Care Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 16 Participants | 21 Participants | 37 Participants |
| Age, Categorical Between 18 and 65 years | 71 Participants | 73 Participants | 144 Participants |
| Disease Strata AML | 67 Participants | 67 Participants | 134 Participants |
| Disease Strata Biphenotypic Leukemia | 0 Participants | 1 Participants | 1 Participants |
| Disease Strata MDS | 26 Participants | 26 Participants | 52 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) White | 79 Participants | 92 Participants | 171 Participants |
| Region of Enrollment United States | 87 participants | 94 participants | 181 participants |
| Sex: Female, Male Female | 36 Participants | 37 Participants | 73 Participants |
| Sex: Female, Male Male | 51 Participants | 57 Participants | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 87 | 1 / 94 |
| other Total, other adverse events | 29 / 87 | 19 / 94 |
| serious Total, serious adverse events | 0 / 87 | 0 / 94 |
Outcome results
Primary
Relapse-free Survival (RFS)
The time that a participant survives without relapse of the disease.
Time frame: 3 years
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| AZA Group | Relapse-free Survival (RFS) | 2.1 years | Standard Deviation 0.43 |
| Standard of Care Group | Relapse-free Survival (RFS) | 1.3 years | Standard Deviation 0.43 |
Secondary
Overall Survival (OS)
Time frame: 3 years
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| AZA Group | Overall Survival (OS) | 2.5 years | Standard Deviation 0.85 |
| Standard of Care Group | Overall Survival (OS) | 2.6 years | Standard Deviation 0.85 |