LeukemiaPhase 2NCT01444742
Clofarabine Plus Low-Dose Cytarabine for Patients With Higher-Risk Myelodysplastic Syndrome (MDS)
A Phase 2 study testing Clofarabine and Cytarabine in people with Leukemia and Myeloproliferative Diseases, 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 clofarabine when given in combination with cytarabine can help to control myelodysplastic syndrome (MDS) after the disease could not be controlled with standard therapy. The safety of this treatment will also be studied. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myeloproliferative Diseases
- What is being tested?
- Clofarabine and Cytarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 81 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Nov 2011to 29 Jan 2017
- 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
- Age >/= 18 years.
- Diagnosis of MDS confirmed within 10 weeks prior to study entry according to World Health Organization (WHO) or French-American-British (FAB) criteria. Patients are either not eligible for or choose not to proceed with a stem cell transplant.
- MDS classified as follows: refractory anemia with excess blasts (RAEB-1) (5%-9% BM blasts); RAEB-2 (10%-19% BM Blasts); chronic myelomonocytic leukemia (CMML) (5%-19% Bone Marrow (BM) blasts); RAEB-t (20%-29% BM blasts) AND/OR by International Prostate Symptom Score (IPSS): intermediate-2 and high risk patients.
- No response, progression, or relapse (according to 2006 International Working Group (IWG) criteria; see section 8 for details) following at least 4 cycles of either azacitidine or decitabine, or following at least 2 cycles of SGI-110, which were completed within the last 2 years - AND/OR - intolerance to azacitidine, decitabine, or SGI-110 defined as drug-related >/= grade 3 hepatic or renal toxicity leading to treatment discontinuation during the preceding 2 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of </= 2.
- Willing to adhere to and comply with all prohibitions and restrictions specified in the protocol.
- Patient (or patient's legally authorized representative) must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study.
Who cannot join
- Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
- Active infection not adequately responding to appropriate antibiotics (i.e. ongoing temperatures of >/= 38 degree Celsius).
- Total bilirubin >/= 1.5 mg/dL and not related to hemolysis or Gilbert's disease. Patients with total bilirubin >/= 1.5 mg/dL to 3 mg/dL are eligible if at least 75% of the bilirubin is indirect.
- Alanine transaminase (ALT/SGPT) or aspartate transaminase (AST/SGOT) >/= 2.5 x the upper limit of normal.
- Serum creatinine > 1.5 mg/dL.
- Female patients who are pregnant or lactating.
Show all 11Show fewer
- Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives [birth control pills], contraceptive injections, intrauterine devices (IUD), double-barrier method [spermicidal jelly or foam with condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the study.
- Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.
- Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy.
- No prior treatment with cytarabine or clofarabine. Prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg, G-CSF, Granulocyte-macrophage colony-stimulating factor (GM-CSF), procrit, aranesp, thrombopoietins) is allowed at any time prior to or during study if considered to be in the best interest of the patient.
- Psychiatric illness or social situation that would limit the patient's ability to comply with study requirements.
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: Clofarabine Plus Low-Dose Cytarabine for the Treatment of Patients With Higher-Risk Myelodysplastic Syndrome (MDS) Who Have Been Relapsing After, or Are Refractory to, Hypomethylator Therapy
The goal of this clinical research study is to learn if clofarabine when given in combination with cytarabine can help to control myelodysplastic syndrome (MDS) after the disease could not be controlled with standard therapy. The safety of this treatment will also be studied.
Clofarabine is designed to interfere with the growth and development of cancer cells.
Cytarabine is designed to insert itself into DNA (the genetic material of cells) of cancer cells and stop the DNA from repairing itself.
Read the detailed description
Induction Cycles:
If you are found to be eligible to take part in the study, on Days 1-5 of each cycle , you will receive clofarabine by vein over 1-2 hours.
On Days 1-7 of each cycle, you will receive cytarabine by injection under the skin over several seconds 2 times a day.
You may receive up to 3 cycles at this dose and schedule (also called "induction cycles"). There are 7 treatment days in each cycle but the total length of one cycle (including rest and recovery period) is usually between 4 and 8 weeks.
Consolidation Cycles:
After you have completed the Induction Cycles, if you show a response to treatment, you can then continue with up to a total of 12 more cycles of therapy, which will be called "consolidation cycles". Not every participant may be able to receive all 12 consolidation cycles. The actual number that you will receive depends on whether or not you maintain the response and how you are able to tolerate ongoing therapy. There will be 4-8 weeks between each consolidation cycle depending on any side effects you may be having and your blood counts.
During consolidation cycles you will receive clofarabine on Days 1-3 by vein over 1-2 hours. You will receive cytarabine by injection under the skin over several seconds 2 times a day .
Induction and Consolidation Cycles:
On the days when you receive clofarabine and cytarabine (Days 1-5 during induction and Days 1-3 during consolidation), the clofarabine will be given about 3-6 hours before the cytarabine injections. You can be taught to give cytarabine injections to yourself. In this case, you can leave the clinic after receiving clofarabine. You will be required to record the injections of cytarabine in a diary unless you receive the treatments while you are in the hospital.
Study Visits:
On Day 1 of every cycle (+/- 7 days):
- You will have a physical exam, including measurements of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 1-2 teaspoons) will be drawn for routine tests.
About 4 weeks after you started your first cycle, you may have a bone marrow aspirate to check the status of the disease. After that, you may have repeat bone marrow aspirates when the doctor thinks it is needed.
It is recommended that you stay in Houston for up to the first 4 weeks of treatment. After that, you will need to return to Houston before each induction cycle. If you continue with the consolidation you can receive these treatments by your local oncologist. However, you have to return to Houston at least every 3 months for your study visits.
Length of Study:
You may continue taking the study drugs for up to 15 cycles. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
This is an investigational study. Clofarabine is FDA approved and commercially available for use in pediatric patients with acute lymphoblastic leukemia. Its use in adults and in patients with MDS is investigational.
Cytarabine is FDA approved and commercially available for use in patients with acute myeloid leukemia (AML).
Up to 80 patients will take part in this study. All be enrolled at MD Anderson.
- Conditions
- Leukemia, Myeloproliferative Diseases
- Being tested
- Clofarabine, Cytarabine
- Keywords
- Leukemia, Myeloproliferative Diseases, Myelodysplastic Syndrome, (MDS), Relapsing, Refractory, Clofarabine, Clofarex, Clolar, Cytarabine, Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride
- Medical subject headings
- Leukemia, Myelodysplastic Syndromes, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClofarabineDrug
Also called Clofarex, Clolar
Induction:
10 mg/m2 by vein over 1-2 hours daily for 5 days (days 1-5)
Consolidation:
10 mg/m2 by vein over 1-2 hours daily for 3 days (days 1-3)
CytarabineDrug
Also called Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride
Induction:
20 mg subcutaneously twice daily for 7 days (days 1-7)
Consolidation:
20 mg subcutaneously twice daily for 5 days (days 1-5)
| Study group | Role | What they receive |
|---|---|---|
| Clofarabine + Cytarabine | Experimental | Induction:
Clofarabine 10 mg/m2 1-2 hours by vein daily for 5 days (days 1-5) Cytarabine 20 mg subcutaneously twice daily for 7 days (days 1-7)
Consolidation:
Clofarabine 10 mg/m2 1-2 hours by vein daily for 3 days (days 1-3) Cytarabine 20 mg subcutaneously twice daily for 5 days (days 1-5) Receives: Drug: Clofarabine; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Complete Response (CR)
Complete Response Criteria (CR must last for at least 4 weeks): Marrow: </= 5% myeloblasts with normal maturation of all cell lines; Persistent dysplasia noted; Blood: Hemoglobin (Hb) >/= 11 g/dL (untransfused, patient not on EPO); Neutrophils >/= 1x109/L (not on myeloid growth factor); Platelets >/= 100 * 109/L (not on thrombopoietic agent); No blasts. Bone marrow aspirate and/or biopsy at the end of course 1 (day 28 +/- 7 days). The method of Thall, Simon, and Estey used to monitor response.
Measured: 4 weeks after first cycle
Secondary outcomes (1)
Overall Survival (OS)
Overall survival defined as the time interval from study entry date to the date of death due to any cause, measured in days/months. Bayesian time-to-event model used to monitor overall survival.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2011 (estimated)
- Study start16 Nov 2011
- Primary completion29 Jan 2017
- Study completion29 Jan 2017
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 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 81 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
- NCT01444742
- Sponsor's protocol ID
- 2011-0660
- Other IDs
- NCI-2011-03436
- Status last verified
- Jun 2018
- First submitted
- 28 Sep 2011
- Last updated
- 3 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clofarabine Plus Low-Dose Cytarabine for the Treatment of Patients With Higher-Risk Myelodysplastic Syndrome (MDS) Who Have Been Relapsing After, or Are Refractory to, Hypomethylator Therapy
- ClinicalTrials.gov ID
- NCT01444742
- Acronym / sponsor ID
- 2011-0660
- Conditions
- Leukemia, Myeloproliferative Diseases
- Keywords
- Leukemia, Myeloproliferative Diseases, Myelodysplastic Syndrome, (MDS), Relapsing, Refractory, Clofarabine, Clofarex
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 16 Nov 2011 (actual)
- Primary completion
- 29 Jan 2017 (actual)
- Study completion
- 29 Jan 2017 (actual)
- First posted
- 3 Oct 2011 (estimated)
- Results
- Posted 31 May 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 clofarabine when given in combination with cytarabine can help to control myelodysplastic syndrome (MDS) after the disease could not be controlled with standard therapy. The safety of this treatment will also be studied.
Clofarabine is designed to interfere with the growth and development of cancer cells.
Cytarabine is designed to insert itself into DNA (the genetic material of cells) of cancer cells and stop the DNA from repairing itself.
Detailed description
Induction Cycles:
If you are found to be eligible to take part in the study, on Days 1-5 of each cycle , you will receive clofarabine by vein over 1-2 hours.
On Days 1-7 of each cycle, you will receive cytarabine by injection under the skin over several seconds 2 times a day.
You may receive up to 3 cycles at this dose and schedule (also called "induction cycles"). There are 7 treatment days in each cycle but the total length of one cycle (including rest and recovery period) is usually between 4 and 8 weeks.
Consolidation Cycles:
After you have completed the Induction Cycles, if you show a response to treatment, you can then continue with up to a total of 12 more cycles of therapy, which will be called "consolidation cycles". Not every participant may be able to receive all 12 consolidation cycles. The actual number that you will receive depends on whether or not you maintain the response and how you are able to tolerate ongoing therapy. There will be 4-8 weeks between each consolidation cycle depending on any side effects you may be having and your blood counts.
During consolidation cycles you will receive clofarabine on Days 1-3 by vein over 1-2 hours. You will receive cytarabine by injection under the skin over several seconds 2 times a day .
Induction and Consolidation Cycles:
On the days when you receive clofarabine and cytarabine (Days 1-5 during induction and Days 1-3 during consolidation), the clofarabine will be given about 3-6 hours before the cytarabine injections. You can be taught to give cytarabine injections to yourself. In this case, you can leave the clinic after receiving clofarabine. You will be required to record the injections of cytarabine in a diary unless you receive the treatments while you are in the hospital.
Study Visits:
On Day 1 of every cycle (+/- 7 days):
- You will have a physical exam, including measurements of your weight and vital signs.
- Your performance status will be recorded.
- Blood (about 1-2 teaspoons) will be drawn for routine tests.
About 4 weeks after you started your first cycle, you may have a bone marrow aspirate to check the status of the disease. After that, you may have repeat bone marrow aspirates when the doctor thinks it is needed.
It is recommended that you stay in Houston for up to the first 4 weeks of treatment. After that, you will need to return to Houston before each induction cycle. If you continue with the consolidation you can receive these treatments by your local oncologist. However, you have to return to Houston at least every 3 months for your study visits.
Length of Study:
You may continue taking the study drugs for up to 15 cycles. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.
This is an investigational study. Clofarabine is FDA approved and commercially available for use in pediatric patients with acute lymphoblastic leukemia. Its use in adults and in patients with MDS is investigational.
Cytarabine is FDA approved and commercially available for use in patients with acute myeloid leukemia (AML).
Up to 80 patients will take part in this study. All be enrolled at MD Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Clofarabine + Cytarabine | Experimental | Drug: Clofarabine, Drug: CytarabineInduction: Clofarabine 10 mg/m2 1-2 hours by vein daily for 5 days (days 1-5) Cytarabine 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: Clofarabine 10 mg/m2 1-2 hours by vein daily for 3 days (days 1-3) Cytarabine 20 mg subcutaneously twice daily for 5 days (days 1-5) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Age >/= 18 years.
- Diagnosis of MDS confirmed within 10 weeks prior to study entry according to World Health Organization (WHO) or French-American-British (FAB) criteria. Patients are either not eligible for or choose not to proceed with a stem cell transplant.
- MDS classified as follows: refractory anemia with excess blasts (RAEB-1) (5%-9% BM blasts); RAEB-2 (10%-19% BM Blasts); chronic myelomonocytic leukemia (CMML) (5%-19% Bone Marrow (BM) blasts); RAEB-t (20%-29% BM blasts) AND/OR by International Prostate Symptom Score (IPSS): intermediate-2 and high risk patients.
- No response, progression, or relapse (according to 2006 International Working Group (IWG) criteria; see section 8 for details) following at least 4 cycles of either azacitidine or decitabine, or following at least 2 cycles of SGI-110, which were completed within the last 2 years - AND/OR - intolerance to azacitidine, decitabine, or SGI-110 defined as drug-related >/= grade 3 hepatic or renal toxicity leading to treatment discontinuation during the preceding 2 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of </= 2.
Key exclusion criteria (11 listed)
- Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
- Active infection not adequately responding to appropriate antibiotics (i.e. ongoing temperatures of >/= 38 degree Celsius).
- Total bilirubin >/= 1.5 mg/dL and not related to hemolysis or Gilbert's disease. Patients with total bilirubin >/= 1.5 mg/dL to 3 mg/dL are eligible if at least 75% of the bilirubin is indirect.
- Alanine transaminase (ALT/SGPT) or aspartate transaminase (AST/SGOT) >/= 2.5 x the upper limit of normal.
- Serum creatinine > 1.5 mg/dL.
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 |
|---|---|---|
| ClofarabineAlso: Clofarex, ClolarInduction: 10 mg/m2 by vein over 1-2 hours daily for 5 days (days 1-5) Consolidation: 10 mg/m2 by vein over 1-2 hours daily for 3 days (days 1-3) | Drug | Clofarabine + Cytarabine |
| CytarabineAlso: Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine HydrochlorideInduction: 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: 20 mg subcutaneously twice daily for 5 days (days 1-5) | Drug | Clofarabine + Cytarabine |
Primary outcome
Number of Participants With Complete Response (CR)
Time frame: 4 weeks after first cycle
Complete Response Criteria (CR must last for at least 4 weeks): Marrow: </= 5% myeloblasts with normal maturation of all cell lines; Persistent dysplasia noted; Blood: Hemoglobin (Hb) >/= 11 g/dL (untransfused, patient not on EPO); Neutrophils >/= 1x109/L (not on myeloid growth factor); Platelets >/= 100 * 109/L (not on thrombopoietic agent); No blasts. Bone marrow aspirate and/or biopsy at the end of course 1 (day 28 +/- 7 days). The method of Thall, Simon, and Estey used to monitor response.
1 secondary outcome
Overall Survival (OS)
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 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, MD 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 Clofarabine and Cytarabine in people with Leukemia and Myeloproliferative Diseases, 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 7 inclusion and 11 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 3 Jul 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 31 May 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?
Number of Participants With Complete Response (CR) (time frame: 4 weeks after first cycle). 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 3 Jul 2018.