Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Leukemia
Conditions
Keywords
Acute Myelogenous Leukemia, AML, Myelodysplastic Syndrome, Leukemia, MDS, Azacytidine, 5-Azacytidine, 5-aza, Vidaza, 5-AZC, AZA-CR, Ladakamycin, Ara-C, Cytarabine, Cytosar, DepoCyt, Cytosine arabinosine hydrochloride, Valproic Acid, VPA, Depakene
Brief summary
Primary Objective: 1\. To evaluate whether 5 azacytidine (5-aza)/valproic acid (VPA) or low dose ara-C produces longer event free survival time in patients age \> or = 60 years with untreated Acute Myeloid Leukemia (AML) or high risk Myelodysplastic Syndrome (MDS) who are typically ineligible for, or not placed on, studies of new agents. Secondary Objective: 1\. To evaluate whether pre-treatment methylation/acetylation status in AML/MDS blasts predicts response to either therapy or whether the ability of the 5 azacytidine + valproic acid combination to induce demethylation or acetylation parallels response.
Detailed description
5-aza is a chemotherapy drug with activity in leukemia and MDS. Researchers hope that VPA will increase the effects of 5-aza. Low-dose Cytarabine (ara-C) is considered the standard of care for the treatment of leukemia and MDS in older patients not eligible for other therapies. Before you can start treatment on this study, you will have what are called screening tests. These tests will help the doctor decide if you are eligible to take part in the study. You will have blood drawn (about 2 teaspoons) for routine tests. You will also have a bone marrow biopsy and aspiration performed. To collect a bone marrow biopsy/aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test. If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of two treatment groups. Participants in one group will receive 5-aza and VPA. Participants in the other group will receive ara-C alone. At first, there will be an equal chance of being assigned to either group. As the study goes along, however, the chance of being assigned to the treatment that has worked best so far will increase. Participants in the 5-aza and VPA group will receive 5-aza as an injection under the skin once a day for 7 days in a row. On these same 7 days, participants in this group will also take VPA by mouth twice a day or 3 times a day based on your weight. Seven (7) days is considered 1 treatment cycle. Both drugs will be taken at the same time. Cycles will be repeated every 4 to 6 weeks. Participants in the ara-C group will receive ara-c twice a day as an injection under the skin for 10 days (1 cycle). Cycles will be repeated every 4 to 6 weeks. You will be monitored with routine blood tests (about 1-2 teaspoons each time) 2-3 times a week during this study. You may receive up to 12 cycles of therapy. You may be taken off study early if the disease gets worse or intolerable side effects occur. Once you go off study, you will have standard follow-up as is required by your primary physician. This is an investigational study. 5-aza is approved by the FDA for MDS. VPA is approved by the FDA for epilepsy. Their use together in this study is experimental. Ara-C is approved for acute myelogenous leukemia. About 70 patients will take part in this study. All will be enrolled at M. D. Anderson.
Interventions
DRUG5-Azacytidine
75 mg/m\^2 daily for 7 days (days 1-7) via subcutaneous injection.
DRUGAra-C
20 mg twice daily via subcutaneous injection for 10 days.
50 mg/m\^2 orally daily days 1-7.
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients must have untreated AML, or untreated MDS with \> 10% blasts in marrow or blood. 2. They must be at least age 60. 3. They must either have a serum creatinine \> 1.9 mg/ml, a serum bilirubin \> 1.9 mg/ml, or a Zubrod performance status of 3 or 4. 4. Alternatively, they must not be candidates for protocols of higher priority. 5. They must provide written consent.
Exclusion criteria
1\) Must not have the cytogenetic abnormalities inv (16), t (16;16) t (8;21), or t (15;17). The relatively good prognoses of patients with these findings do not warrant use of 5 azacytidine, + valproic acid or low-dose ara-C (LDAC).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Response | Evaluated every 3 weeks, following 4 courses (16/24 weeks ) and till study end | Patient response defined by: Death, Resistant to Therapy \[no major hematologic improvement using International Myelodysplastic Syndromes (MDS) Working Group (Cheson B, Bennett J, Kantarjian H et al, Blood 2006) criteria after a maximum of 4 courses\], or Relapse. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: 09/20/05 through 11/01/06. All participants recruited at UT MD Anderson Cancer Center.
Pre-assignment details
Eleven (11) patients were registered, one (1) patient was not eligible and was taken off study prior to receiving study drug.
Participants by arm
| Arm | Count |
|---|---|
| 5-Aza + VPA 5-Azacytidine (5-Aza) 75 mg/m\^2 subcutaneously daily + Valproic Acid (VPA) 50 mg/m\^2 orally daily, each for 7 days | 4 |
| Ara-C Low-Dose Cytarabine (Ara-C) 20 mg twice daily subcutaneously for 10 days. | 6 |
| Total | 10 |
Baseline characteristics
| Characteristic | 5-Aza + VPA | Ara-C | Total |
|---|---|---|---|
| Age Continuous | 75 years | 76.5 years | 75.5 years |
| Region of Enrollment United States | 4 participants | 6 participants | 10 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 5 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 4 | 4 / 6 |
| serious Total, serious adverse events | 4 / 4 | 6 / 6 |
Outcome results
Primary
Number of Participants With Response
Patient response defined by: Death, Resistant to Therapy \[no major hematologic improvement using International Myelodysplastic Syndromes (MDS) Working Group (Cheson B, Bennett J, Kantarjian H et al, Blood 2006) criteria after a maximum of 4 courses\], or Relapse.
Time frame: Evaluated every 3 weeks, following 4 courses (16/24 weeks ) and till study end
Population: The analysis was per intention to treat. One participant was inevaluable for response.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5-Aza + VPA | Number of Participants With Response | Death | 0 Participants |
| 5-Aza + VPA | Number of Participants With Response | Resistant to Therapy | 4 Participants |
| 5-Aza + VPA | Number of Participants With Response | Relapse | 0 Participants |
| Ara-C | Number of Participants With Response | Death | 0 Participants |
| Ara-C | Number of Participants With Response | Resistant to Therapy | 5 Participants |
| Ara-C | Number of Participants With Response | Relapse | 0 Participants |