Myelodysplastic SyndromePhase 2NCT00903760
Decitabine and Clofarabine in Higher Risk Myelodysplastic Syndromes (MDS)
A Phase 2 study testing Decitabine and Clofarabine in people with Myelodysplastic Syndrome, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to learn if sequential administration of decitabine and clofarabine can help to control MDS better than decitabine alone. The safety of this drug combination will also be studied. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome
- What is being tested?
- Decitabine and Clofarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to Jun 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients with higher risk MDS (IPSS int-2 or high, or >/= 10% blasts as defined by WHO or FAB). - No prior intensive chemotherapy or high-dose cytarabine (>/= 1 g/m2). - Prior biologic therapies (</= 1 cycle of prior decitabine or azacitidine), targeted therapies, or single agent chemotherapy is allowed. - Off chemotherapy for 2 weeks prior to entering this study with no toxic effects of that therapy, unless there is evidence of rapidly progressive disease. - Hydroxyurea is permitted for control of counts prior to treatment. - Hematopoietic growth factors are allowed. .
- Age >/= 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status </= 2.
- Have adequate renal function (serum creatinine </= 1.5 mg/dL)
- Serum bilirubin </= 1.5 x upper limit of normal (ULN)
- Aspartate transaminase (AST) or alanine transaminase (ALT) </= 2.5 x ULN
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- Alkaline phosphatase </= 2.5 x ULN
- Provide signed written informed consent.
- Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
- Female patients of childbearing potential must have a negative pregnancy test within 2 weeks prior to enrollment.
- Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.
Who cannot join
- Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
- Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy.
- Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment.
- Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
- Pregnant or lactating patients.
- Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results
- Any concurrent malignancy (with the exception of exclusion # 8)
- Exceptions to inclusion # 7: a) Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed; b) Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Randomized Study of Decitabine Alternating With Clofarabine Versus Decitabine Until Failure in Patients With Higher Risk Myelodysplastic Syndromes (MDS)
The goal of this clinical research study is to learn if sequential administration of decitabine and clofarabine can help to control MDS better than decitabine alone. The safety of this drug combination will also be studied.
Read the detailed description
The Study Drugs:
Decitabine is designed to damage cells' DNA (genetic material), which may cause myelodysplastic marrow cells to work more like normal marrow cells.
Clofarabine is designed to interfere with the growth and development of abnormal marrow cells.
Study Groups:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups.
- If you are in Group 1, you will receive decitabine and clofarabine.
- If you are in Group 2, you will receive only decitabine.
Study Drug Administration:
Each cycle is 4-8 weeks depending on how you tolerate the drug and how the MDS responds to it.
Group 1:
If you are in Group 1, you will receive the drugs in an alternating series of cycles. This means that you will receive decitabine for the first 3 cycles, then clofarabine for the next 3 cycles, and then repeat. This pattern will continue for up to 24 cycles.
On Days 1-5 of Cycles 1-3, 7-9, 13-15, and 19-21, you will receive decitabine by vein over 1-2 hours.
On Days 1-5 of Cycles 4-6, 10-12, 16-18, and 22-24, you will receive clofarabine by vein over 1-2 hours.
Group 2:
If you are in Group 2, you will receive decitabine by vein over 1-2 hours on Days 1-5 of every cycle.
Study Visits:
On Day 1 of every cycle, the following tests and procedures will be performed:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
Once a week, blood (about 1-2 teaspoons) will be drawn for routine tests.
At the end of Cycle 3, you will have a bone marrow aspirate to check the status of the disease.
If the disease has not gone into remission after Cycle 3, your next bone marrow aspirate will depend on your group. If you are in Group 1, you may have another aspirate about 3 weeks after you begin Cycle 4. After that, you may have an aspirate every 2 weeks (or more often if your doctor feels it is needed) until the response (or lack thereof) is confirmed. If you are in Group 2, you may not have another bone marrow aspirate until after the end of Cycle 6.
You will need to stay in Houston to receive the study drug(s). When you have study visits where you are not receiving study drug(s), these tests can be performed by your local doctor. If your MD Anderson leukemia doctor approves, your study drug can be administered outside MD Anderson by your local doctor.
Length of Study:
You will be on study for up to 24 cycles. You will be taken off study early if the disease gets worse or you experience any intolerable side effects.
Follow-up Visits:
After your last dose of study drug, you will have follow-up visits. You will only have these visits if the disease has responded to the study drug.
- Once a month, blood (about 1 tablespoon) will be drawn routine tests. This can be done at home through your local cancer doctor.
- Every 6 months, you will return to Houston for a physical exam and blood (about 1 tablespoon) will be drawn for routine tests.
This is an investigational study. Clofarabine is FDA approved and commercially available for use in pediatric patients with a type of blood cancer (acute lymphocytic leukemia -- ALL). Its use in patients with MDS is investigational.
Decitabine is FDA approved and commercially available for use in patients with MDS.
Up to 80 patients will take part in this study. All will be enrolled at MD Anderson.
- Conditions
- Myelodysplastic Syndrome
- Being tested
- Decitabine, Clofarabine
- Keywords
- Myelodysplastic Syndrome, MDS, Leukemia, Decitabine, clofarabine, Dacogen®, Clolar®
- Medical subject headings
- Myelodysplastic Syndromes, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Also called Dacogen®
Decitabine 20 mg/m^2 by vein daily over 1-2 hours for 5 days for both Group 1 and Group 2. Group 1 receives decitabine on Days 1-5 of Cycles 1-3, 7-9, 13-15, and 19-21; and Group 2 is on Days 1-5 of every cycle.
ClofarabineDrug
Also called Clolar®
Clofarabine 10 mg/m^2 by vein daily over 1-2 hours for 5 days on Days 1-5 of Cycles 4-6, 10-12, 16-18, and 22-24.
| Study group | Role | What they receive |
|---|---|---|
| Decitabine + Clofarabine | Experimental | Drug delivery intravenously (IV) in alternating series of cycles (Decitabine 20 mg/m^2 for 5 days first 3 cycles, then Clofarabine 10 mg/m^2 five days for next 3 cycles), pattern repeats for up to 24 cycles. Receives: Drug: Decitabine; Drug: Clofarabine |
| Decitabine | Experimental | Decitabine 20 mg/m^2 IV daily for 5 days for a total of 24 courses. Receives: Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event Free Survival (EFS) at 1 Year
Percentage of participants with event free survival at 1 year. Event free survival (EFS) where event is defined as either death or transformation to acute myeloid leukemia (AML) (marrow and/or blood blasts >/= 20%)
Measured: Assessed at 12 months/1 year
Secondary outcomes (1)
Participant Response
Responses: Complete Remission (CR): Normalization peripheral blood \& bone marrow </= 5% bone marrow blasts, no evidence dysplasia; peripheral blood granulocyte >/= 1.0 x 10^9/L, \& platelet>/= 100 x 10^9/L. Partial Remission: all CR criteria if abnormal before treatment except marrow blasts decrease =/> 50% compared to pretreatment or a less-advanced MDS disease classification than prior to treatment. Hematologic Improvement: Response maintained 8+ weeks: Hemoglobin (pretreatment < 11 g/dL): improves 1.5 g/dL or reduced by 4 units of red blood cell (RBC) transfusions in 8 weeks compared with pretreatment transfusions in 8 weeks; or Platelet (pretreatment < 100 x 10^9/L): absolute increase >/= 30 x 10^9/L, starting platelet > 20 x 10^9/L OR increase < 20 x 10^9/L to > 20 x 10^9/L and =/> 100%. Neutrophil (pretreatment < 1 x 10^9/L): increase 100% \& absolute increase > 0.5 x 10^9/L.
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2009 (estimated)
- Study startJan 2010
- Primary completionJun 2015
- Study completionJun 2015
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 Myelodysplastic SyndromeStudies 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
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Sponsor
- Investigators
- Guillermo Garcia-Manero, M.D., Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00903760
- Sponsor's protocol ID
- 2008-0092
- Other IDs
- NCI-2011-00263
- Status last verified
- Oct 2018
- First submitted
- 14 May 2009
- Last updated
- 15 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Study of Decitabine Alternating With Clofarabine Versus Decitabine Until Failure in Patients With Higher Risk Myelodysplastic Syndromes (MDS)
- ClinicalTrials.gov ID
- NCT00903760
- Acronym / sponsor ID
- 2008-0092
- Conditions
- Myelodysplastic Syndrome
- Keywords
- Myelodysplastic Syndrome, MDS, Leukemia, Decitabine, clofarabine, Dacogen®, Clolar®
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- Jan 2010
- Primary completion
- Jun 2015 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 18 May 2009 (estimated)
- Results
- Posted 15 Nov 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to learn if sequential administration of decitabine and clofarabine can help to control MDS better than decitabine alone. The safety of this drug combination will also be studied.
Detailed description
The Study Drugs:
Decitabine is designed to damage cells' DNA (genetic material), which may cause myelodysplastic marrow cells to work more like normal marrow cells.
Clofarabine is designed to interfere with the growth and development of abnormal marrow cells.
Study Groups:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups.
- If you are in Group 1, you will receive decitabine and clofarabine.
- If you are in Group 2, you will receive only decitabine.
Study Drug Administration:
Each cycle is 4-8 weeks depending on how you tolerate the drug and how the MDS responds to it.
Group 1:
If you are in Group 1, you will receive the drugs in an alternating series of cycles. This means that you will receive decitabine for the first 3 cycles, then clofarabine for the next 3 cycles, and then repeat. This pattern will continue for up to 24 cycles.
On Days 1-5 of Cycles 1-3, 7-9, 13-15, and 19-21, you will receive decitabine by vein over 1-2 hours.
On Days 1-5 of Cycles 4-6, 10-12, 16-18, and 22-24, you will receive clofarabine by vein over 1-2 hours.
Group 2:
If you are in Group 2, you will receive decitabine by vein over 1-2 hours on Days 1-5 of every cycle.
Study Visits:
On Day 1 of every cycle, the following tests and procedures will be performed:
- You will have a physical exam, including measurement of your weight and vital signs.
- Your performance status will be recorded.
Once a week, blood (about 1-2 teaspoons) will be drawn for routine tests.
At the end of Cycle 3, you will have a bone marrow aspirate to check the status of the disease.
If the disease has not gone into remission after Cycle 3, your next bone marrow aspirate will depend on your group. If you are in Group 1, you may have another aspirate about 3 weeks after you begin Cycle 4. After that, you may have an aspirate every 2 weeks (or more often if your doctor feels it is needed) until the response (or lack thereof) is confirmed. If you are in Group 2, you may not have another bone marrow aspirate until after the end of Cycle 6.
You will need to stay in Houston to receive the study drug(s). When you have study visits where you are not receiving study drug(s), these tests can be performed by your local doctor. If your MD Anderson leukemia doctor approves, your study drug can be administered outside MD Anderson by your local doctor.
Length of Study:
You will be on study for up to 24 cycles. You will be taken off study early if the disease gets worse or you experience any intolerable side effects.
Follow-up Visits:
After your last dose of study drug, you will have follow-up visits. You will only have these visits if the disease has responded to the study drug.
- Once a month, blood (about 1 tablespoon) will be drawn routine tests. This can be done at home through your local cancer doctor.
- Every 6 months, you will return to Houston for a physical exam and blood (about 1 tablespoon) will be drawn for routine tests.
This is an investigational study. Clofarabine is FDA approved and commercially available for use in pediatric patients with a type of blood cancer (acute lymphocytic leukemia -- ALL). Its use in patients with MDS is investigational.
Decitabine is FDA approved and commercially available for use in patients with MDS.
Up to 80 patients will take part in this study. All will be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Decitabine + Clofarabine | Experimental | Drug: Decitabine, Drug: ClofarabineDrug delivery intravenously (IV) in alternating series of cycles (Decitabine 20 mg/m^2 for 5 days first 3 cycles, then Clofarabine 10 mg/m^2 five days for next 3 cycles), pattern repeats for up to 24 cycles. |
| Decitabine | Experimental | Drug: DecitabineDecitabine 20 mg/m^2 IV daily for 5 days for a total of 24 courses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with higher risk MDS (IPSS int-2 or high, or >/= 10% blasts as defined by WHO or FAB). - No prior intensive chemotherapy or high-dose cytarabine (>/= 1 g/m2). - Prior biologic therapies (</= 1 cycle of prior decitabine or azacitidine), targeted therapies, or single agent chemotherapy is allowed. - Off chemotherapy for 2 weeks prior to entering this study with no toxic effects of that therapy, unless there is evidence of rapidly progressive disease. - Hydroxyurea is permitted for control of counts prior to treatment. - Hematopoietic growth factors are allowed. .
- Age >/= 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status </= 2.
- Have adequate renal function (serum creatinine </= 1.5 mg/dL)
- Serum bilirubin </= 1.5 x upper limit of normal (ULN)
Key exclusion criteria (8 listed)
- Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
- Use of investigational agents within 30 days or any anticancer therapy within 2 weeks before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy.
- Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment.
- Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment)
- Pregnant or lactating patients.
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 |
|---|---|---|
| DecitabineAlso: Dacogen®Decitabine 20 mg/m^2 by vein daily over 1-2 hours for 5 days for both Group 1 and Group 2. Group 1 receives decitabine on Days 1-5 of Cycles 1-3, 7-9, 13-15, and 19-21; and Group 2 is on Days 1-5 of every cycle. | Drug | Decitabine, Decitabine + Clofarabine |
| ClofarabineAlso: Clolar®Clofarabine 10 mg/m^2 by vein daily over 1-2 hours for 5 days on Days 1-5 of Cycles 4-6, 10-12, 16-18, and 22-24. | Drug | Decitabine + Clofarabine |
Primary outcome
Event Free Survival (EFS) at 1 Year
Time frame: Assessed at 12 months/1 year
Percentage of participants with event free survival at 1 year. Event free survival (EFS) where event is defined as either death or transformation to acute myeloid leukemia (AML) (marrow and/or blood blasts >/= 20%)
1 secondary outcome
Participant Response
Time frame: Up to 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink provided by the sponsor.
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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.
Guillermo Garcia-Manero, M.D. principal investigator
M.D. Anderson 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 2 study testing Decitabine and Clofarabine in people with Myelodysplastic Syndrome, run by M.D. Anderson 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 11 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: finished, as of the sponsor's last update on 15 Nov 2018. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Event Free Survival (EFS) at 1 Year (time frame: Assessed at 12 months/1 year). 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 15 Nov 2018.