LeukemiaPhase 1NCT00234000
Azacitidine and Arsenic Trioxide in Treating Patients With Myelodysplastic Syndromes
A Phase 1 study testing arsenic trioxide and azacitidine in people with Leukemia and Myelodysplastic Syndromes, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as azacitidine and arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myelodysplastic Syndromes
- What is being tested?
- arsenic trioxide and azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2007to Feb 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of MDS by standard criteria. Patients within each of the FAB diagnostic groups of RA, RARS, RAEB, RAEBt, and CMML are eligible. For patients with lower-risk MDS only: documented red blood cell dependence, defined as the inability to maintain a hematocrit of > 25% without transfusion support.
- Adequate marrow iron stores
- In patients with serum erythropoietin less than 200 IU/mL at screening, failure to have responded to a 2 to 3 month trial of recombinant erythropoietin
- Serum creatinine or serum bilirubin < 1.5 times the upper limit of normal; higher levels are acceptable if ALT levels < 2 x upper limits of normal
- Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine/treatment.
- Women of childbearing potential should be advised to avoid becoming pregnant and should be advised to not father a child while receiving treatment with azacitidine
- Age > 18 years
Who cannot join
- Treatment with growth factors within the 30 days before first treatment with ATO/Azacitidine, except that patients with serum erythropoietin < 200 IU/mL who failed to respond to a trial with EPO are not excluded regardless of the time since last EPO
- Treatment with cytotoxic or experimental agents within 30 days before first treatment with ATO/Azacitidine
- Absolute QT interval > 460 msec in the presence of adequate serum potassium and magnesium values
- Active serious infections that are not controlled by antibiotics
- Pregnant or lactating women
- Inability or unwillingness to comply with the treatment protocol, follow-up, or research tests
- NYHA Class III or IV heart failure
- Poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, 90095-1781
About this study
Official title: A Phase I Multicenter Study of Arsenic Trioxide and Azacitidine in Patients With Myelodysplastic Syndromes
RATIONALE: Drugs used in chemotherapy, such as azacitidine and arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of azacitidine when given together with arsenic trioxide and to see how well they work in treating patients with myelodysplastic syndromes.
Read the detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of azacitidine when given in combination with arsenic trioxide in patients with myelodysplastic syndromes (MDS). (Phase I)
- Determine the safety and tolerability of this regimen in these patients. (Phase I)
- Determine the major hematologic response (erythroid response) rate in patients with transfusion-dependent lower-risk MDS treated with this regimen. (Phase II)
- Determine complete and partial remission rates in patients with higher-risk MDS treated with this regimen. (Phase II)
- Determine the toxicity profile of this regimen in these patients. (Phase I)
Secondary
- Determine time to disease progression in patients treated with this regimen. (Phase I and II)
- Determine the overall and progression-free survival of patients treated with this regimen. (Phase I and II)
OUTLINE: This is an multicenter, open-label, phase I, dose escalation study of azacitidine followed by a phase II study. Patients enrolled in the phase II portion are stratified according to baseline International Scoring System score (lower-risk myelodysplastic syndromes [MDS] vs higher-risk MDS).
- Phase I: Patients receive azacitidine subcutaneously once daily on days 1-5 and arsenic trioxide IV over 1-4 hours on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with stable disease may receive up to 8 courses of therapy. Patients with responding disease may continue to receive study therapy until a major response or a complete remission is achieved.
Cohorts of 3-6 patients receive escalating doses of azacitidine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive arsenic trioxide as in phase I and azacitidine as in phase I at one dose level below the MTD determined in phase I.
After the completion of study treatment, patients are followed at 4 weeks and then every 3-12 months for survival.
PROJECTED ACCRUAL: Approximately 3-18 patients will be accrued for the phase I portion of this study. A total of 60 patients (30 per stratum) will be accrued for the phase II portion of this study.
- Conditions
- Leukemia, Myelodysplastic Syndromes
- Being tested
- arsenic trioxide, azacitidine
- Keywords
- refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, refractory anemia with ringed sideroblasts, refractory anemia, chronic myelomonocytic leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes, Anemia, Refractory, with Excess of Blasts, Anemia, Refractory, Leukemia, Myelomonocytic, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
arsenic trioxideDrug
Also called ATO
Each 28-day treatment cycle will include dosing for 2 days per week of ATO. Subjects will recieve 1 mg/mL each dosing day.
azacitidineDrug
Each 28-day treatment cycle will include dosing the first five days of cycle with Azacitidine. Cohorts of three to six patients will each receive 25, 50, and 75 mg/m2/d injected subcutaneously.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | see description in intervention Receives: Drug: arsenic trioxide; Drug: azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability as assessed by NCI CTCAE v3.0 (Phase I)
Measured: Every 28 days upto 8 months
Secondary outcomes (2)
Time to disease progression
Measured: Participants are folowed for an average of 1 year after completion of study treatment
Overall survival
Measured: Participants are followed every 3-12 months for survival
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2005 (estimated)
- Study startFeb 2007
- Primary completionFeb 2009
Why it stopped: The study was closed due to poor enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Jonsson Comprehensive 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- CTI BioPharma, Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- Gary J. Schiller, MD, Principal investigator, Jonsson Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00234000
- Sponsor's protocol ID
- CDR0000442931
- Other IDs
- UCLA-0408087
- Status last verified
- Aug 2012
- First submitted
- 5 Oct 2005
- Last updated
- 31 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Multicenter Study of Arsenic Trioxide and Azacitidine in Patients With Myelodysplastic Syndromes
- ClinicalTrials.gov ID
- NCT00234000
- Acronym / sponsor ID
- CDR0000442931
- Conditions
- Leukemia, Myelodysplastic Syndromes
- Keywords
- refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, refractory anemia with ringed sideroblasts, refractory anemia, chronic myelomonocytic leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was closed due to poor enrollment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- CTI BioPharma, Celgene Corporation
- Study start
- Feb 2007
- Primary completion
- Feb 2009 (actual)
- First posted
- 6 Oct 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as azacitidine and arsenic trioxide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of azacitidine when given together with arsenic trioxide and to see how well they work in treating patients with myelodysplastic syndromes.
Detailed description
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of azacitidine when given in combination with arsenic trioxide in patients with myelodysplastic syndromes (MDS). (Phase I)
- Determine the safety and tolerability of this regimen in these patients. (Phase I)
- Determine the major hematologic response (erythroid response) rate in patients with transfusion-dependent lower-risk MDS treated with this regimen. (Phase II)
- Determine complete and partial remission rates in patients with higher-risk MDS treated with this regimen. (Phase II)
- Determine the toxicity profile of this regimen in these patients. (Phase I)
Secondary
- Determine time to disease progression in patients treated with this regimen. (Phase I and II)
- Determine the overall and progression-free survival of patients treated with this regimen. (Phase I and II)
OUTLINE: This is an multicenter, open-label, phase I, dose escalation study of azacitidine followed by a phase II study. Patients enrolled in the phase II portion are stratified according to baseline International Scoring System score (lower-risk myelodysplastic syndromes [MDS] vs higher-risk MDS).
- Phase I: Patients receive azacitidine subcutaneously once daily on days 1-5 and arsenic trioxide IV over 1-4 hours on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with stable disease may receive up to 8 courses of therapy. Patients with responding disease may continue to receive study therapy until a major response or a complete remission is achieved.
Cohorts of 3-6 patients receive escalating doses of azacitidine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients receive arsenic trioxide as in phase I and azacitidine as in phase I at one dose level below the MTD determined in phase I.
After the completion of study treatment, patients are followed at 4 weeks and then every 3-12 months for survival.
PROJECTED ACCRUAL: Approximately 3-18 patients will be accrued for the phase I portion of this study. A total of 60 patients (30 per stratum) will be accrued for the phase II portion of this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: arsenic trioxide, Drug: azacitidinesee description in intervention |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Confirmed diagnosis of MDS by standard criteria. Patients within each of the FAB diagnostic groups of RA, RARS, RAEB, RAEBt, and CMML are eligible. For patients with lower-risk MDS only: documented red blood cell dependence, defined as the inability to maintain a hematocrit of > 25% without transfusion support.
- Adequate marrow iron stores
- In patients with serum erythropoietin less than 200 IU/mL at screening, failure to have responded to a 2 to 3 month trial of recombinant erythropoietin
- Serum creatinine or serum bilirubin < 1.5 times the upper limit of normal; higher levels are acceptable if ALT levels < 2 x upper limits of normal
- Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine/treatment.
Key exclusion criteria (8 listed)
- Treatment with growth factors within the 30 days before first treatment with ATO/Azacitidine, except that patients with serum erythropoietin < 200 IU/mL who failed to respond to a trial with EPO are not excluded regardless of the time since last EPO
- Treatment with cytotoxic or experimental agents within 30 days before first treatment with ATO/Azacitidine
- Absolute QT interval > 460 msec in the presence of adequate serum potassium and magnesium values
- Active serious infections that are not controlled by antibiotics
- Pregnant or lactating women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| arsenic trioxideAlso: ATOEach 28-day treatment cycle will include dosing for 2 days per week of ATO. Subjects will recieve 1 mg/mL each dosing day. | Drug | Arm 1 |
| azacitidineEach 28-day treatment cycle will include dosing the first five days of cycle with Azacitidine. Cohorts of three to six patients will each receive 25, 50, and 75 mg/m2/d injected subcutaneously. | Drug | Arm 1 |
Primary outcome
Safety and tolerability as assessed by NCI CTCAE v3.0 (Phase I)
Time frame: Every 28 days upto 8 months
2 secondary outcomes
Time to disease progression
Time frame: Participants are folowed for an average of 1 year after completion of study treatment
Overall survival
Time frame: Participants are followed every 3-12 months for survival
Results and safety
The study was stopped early (reason given: The study was closed due to poor enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary J. Schiller, MD principal investigator
Jonsson Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing arsenic trioxide and azacitidine in people with Leukemia and Myelodysplastic Syndromes, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 31 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study was closed due to poor enrollment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability as assessed by NCI CTCAE v3.0 (Phase I) (time frame: Every 28 days upto 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2020.