Acute Myelogenous LeukemiaPhase 2NCT00382590
Azacytidine With Valproic Acid Versus Ara-C in Acute Myeloid Leukemia (AML)/ Myelodysplastic Syndrome (MDS) Patients
A Phase 2 study testing 5-Azacytidine, Ara-C and Valproic Acid (VPA) in people with Acute Myelogenous Leukemia and Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Acute Myelogenous Leukemia, Myelodysplastic Syndrome, Leukemia
- What is being tested?
- 5-Azacytidine, Ara-C and Valproic Acid (VPA)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2005to Feb 2008
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have untreated AML, or untreated MDS with > 10% blasts in marrow or blood.
- They must be at least age 60.
- 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.
- Alternatively, they must not be candidates for protocols of higher priority.
- They must provide written consent.
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Phase II Study of the Combination of 5-Azacytidine With Valproic Acid (VPA) Versus Low-Dose Ara-C in Patients With AML/MDS Not Eligible for Other Studies
Primary Objective:
- 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:
- 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.
Read the 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.
- Being tested
- 5-Azacytidine, Ara-C, Valproic Acid (VPA)
- 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
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-AzacytidineDrug
Also called Azacytidine, 5-aza, Vidaza, 5-AZC
75 mg/m^2 daily for 7 days (days 1-7) via subcutaneous injection.
Ara-CDrug
Also called Cytarabine, Cytosar, DepoCyt, Cytosine arabinosine hydrochloride
20 mg twice daily via subcutaneous injection for 10 days.
Valproic Acid (VPA)Drug
Also called VPA, Depakene
50 mg/m^2 orally daily days 1-7.
| Study group | Role | What they receive |
|---|---|---|
| 5-Aza + VPA | Active comparator | 5-Azacytidine (5-Aza) 75 mg/m^2 subcutaneously daily + Valproic Acid (VPA) 50 mg/m^2 orally daily, each for 7 days Receives: Drug: 5-Azacytidine; Drug: Valproic Acid (VPA) |
| Ara-C | Active comparator | Low-Dose Ara-C 20 mg twice daily subcutaneously for 10 days. Receives: Drug: Ara-C |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Evaluated every 3 weeks, following 4 courses (16/24 weeks ) and till study end
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2006 (estimated)
- Study startAug 2005
- Primary completionFeb 2008
- Study completionFeb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myelogenous LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Guillermo Garcia-Manero, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00382590
- Sponsor's protocol ID
- 2005-0177
- Status last verified
- Aug 2012
- First submitted
- 27 Sep 2006
- Last updated
- 7 Aug 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes