Myelodysplastic SyndromePhase 1NCT01003678
Safety and Tolerability of Oral Clofarabine in Intermediate to High Risk Myelodysplastic Patients
A Phase 1 study testing Clofarabine in people with Myelodysplastic Syndrome, run by Roswell Park Cancer Institute at 1 site in United States.
Trial summary
This is a Phase I trial for patients with intermediate or high risk myelodysplastic syndrome (MDS). The study agent, clofarabine, is produced by Genzyme Pharmaceuticals. 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?
- Clofarabine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Oct 2013
- 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
- Provide signed written informed consent.
- Patients with MDS must have IPSS score that falls in the intermediate or high risk disease (intermediate 1 will have to be transfusion dependent).
- Patients may have received up to two prior therapies for MDS including one hypomethylating agent and/or a biologic agent (biologic agents include GM-CSF or equivalent, danazol or equivalent, Sunitinib, Revlimid, ATG, or a vaccine).
- Age ≥ 18
- Have adequate renal and hepatic functions as indicated by the following laboratory values:
- Serum creatinine ≤ 1 mg/dL; if serum creatinine >l mg/dL, then the estimated glomerular filtration rate (GFR) must be >50 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation.
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- Serum bilirubin ≤1.5 mg/dL x upper limit of normal (ULN)
- Aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 x ULN
- Alkaline phosphatase ≤2.5 x ULN
- 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 serum 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
- 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.
- Active CNS disease
- 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.
- Have had any prior treatment with clofarabine
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- Have had a diagnosis of another malignancy, unless the patient has been disease free for at least 3 years following the completion of curative intent therapy, with the following exceptions:
- 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.
- 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.
- Have prior positive test for the Human Immunodeficiency Virus (HN).
- Have prior positive test for the Human Immunodeficiency Virus (HN).
- Have currently active gastrointestinal disease, or prior surgery that may affect the ability of the patient to absorb oral clofarabine.
- Patients taking proton pump inhibitors such as omeprazole (Prilosec®), lansoprazole (Prevacid®), or esomeprazole (Nexium®). Those who cannot stop taking these drugs should be switched to H2 blockers such as famotidine (Pepcid®)or ranitidine (Zantac®).
- Patients taking alternative medicines (such as herbal or botanical) are not permitted.
Trial locations and contacts
1 site in 1 country.
United States1 site
Roswell Park Cancer Institute
Buffalo, New York, 14263
About this study
Official title: A Phase I Study Evaluating the Safety and Tolerability of Oral Clofarabine in Intermediate to High Risk Myelodysplastic Patients
This is a Phase I trial for patients with intermediate or high risk myelodysplastic syndrome (MDS).
The study agent, clofarabine, is produced by Genzyme Pharmaceuticals.
Read the detailed description
The specific purpose of the study is to determine the safety, maximum tolerated dose (MTD) and recommended Phase II dose of clofarabine in patients with MDS.
- We will start at a dose of 1 mg daily.
- We will treat a group of 3 patients with clofarabine at that dose level.
- If there are no severe side effects seen at that dose level, then the next group of 3 patients will receive a higher dose.
- Treatment of groups of 3 patients will continue at higher dose levels until severe side-effects are noted.
- If more than 1 of the 3 patients experiences a severe side effect, dosing will be stopped at that level.
- If only one of the three patients experience a severe side effect, then three more patients will be treated, at that dose level and if they too experience severe side effects, then dose escalation will be stopped and the maximum tolerated dose will be determined.
- 10 more patients will be enrolled at the maximum tolerated dose.
- There will be up to 5 dose levels tested.
- We plan to test how much of the drugs are in the patient's blood at different times, and the levels of certain proteins in their blood.
- Conditions
- Myelodysplastic Syndrome
- Being tested
- Clofarabine
- Keywords
- Myelodysplastic syndrome, Clofarabine, low-dose oral clofarabine, intermediate risk Myelodysplastic syndrome, high risk Myelodysplastic syndrome
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClofarabineDrug
Dose Escalation Schedule - Level 1: 1 mg daily x 5 days (orally) followed by 23 days off drug.
Levels 2, 3, 4 and 5 are: 3, 5, 10 and 15 mg daily x 5 days followed by 23 days off drug.
| Study group | Role | What they receive |
|---|---|---|
| Level 1 | Experimental | 1 mg daily for 5 consecutive days followed by 23 days off drug Receives: Drug: Clofarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety, maximum tolerated dose (MTD) and recommended phase II dose of Clofarabine in patients with myelodysplastic syndrome (MDS).
Measured: Up to 6 months
Secondary outcomes (5)
To determine the efficacy of Clofarabine in patients with MDS
Measured: Up to 6 months
To determine the differences in clofarabine triphosphate levels in cells following clofarabine treatment
Measured: Pre, Day 1: Hourly for 6 hours, Pre Day 5:Hourly for 5 hours
Determine the differences in clofarabine plasma levels following clofarabine treatment
Measured: Pre, Day 1: Hourly for 6 hours, Pre Day 5:Hourly for 5 hours
Evaluate the effect of clofarabine on DNA methylation
Measured: Pre and Day 1
Estimate post-treatment p53R2levels in patients treated at the MTD (in the expanded cohort)
Measured: At 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2009 (estimated)
- Study startOct 2009
- Primary completionJun 2013
- Study completionOct 2013
Why it stopped: Drug provider withdrew support
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by Roswell Park Cancer InstituteThe 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
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Roswell Park Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Sponsor
- Investigators
- Wetzler Meir, MD, Principal investigator, Roswell Park Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01003678
- Sponsor's protocol ID
- I 144208
- Status last verified
- Jun 2016
- First submitted
- 27 Oct 2009
- Last updated
- 3 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Evaluating the Safety and Tolerability of Oral Clofarabine in Intermediate to High Risk Myelodysplastic Patients
- ClinicalTrials.gov ID
- NCT01003678
- Acronym / sponsor ID
- I 144208
- Conditions
- Myelodysplastic Syndrome
- Keywords
- Myelodysplastic syndrome, Clofarabine, low-dose oral clofarabine, intermediate risk Myelodysplastic syndrome, high risk Myelodysplastic syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Drug provider withdrew support
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Roswell Park Cancer InstituteUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- Oct 2009
- Primary completion
- Jun 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 29 Oct 2009 (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.
This is a Phase I trial for patients with intermediate or high risk myelodysplastic syndrome (MDS).
The study agent, clofarabine, is produced by Genzyme Pharmaceuticals.
Detailed description
The specific purpose of the study is to determine the safety, maximum tolerated dose (MTD) and recommended Phase II dose of clofarabine in patients with MDS.
- We will start at a dose of 1 mg daily.
- We will treat a group of 3 patients with clofarabine at that dose level.
- If there are no severe side effects seen at that dose level, then the next group of 3 patients will receive a higher dose.
- Treatment of groups of 3 patients will continue at higher dose levels until severe side-effects are noted.
- If more than 1 of the 3 patients experiences a severe side effect, dosing will be stopped at that level.
- If only one of the three patients experience a severe side effect, then three more patients will be treated, at that dose level and if they too experience severe side effects, then dose escalation will be stopped and the maximum tolerated dose will be determined.
- 10 more patients will be enrolled at the maximum tolerated dose.
- There will be up to 5 dose levels tested.
- We plan to test how much of the drugs are in the patient's blood at different times, and the levels of certain proteins in their blood.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Level 1 | Experimental | Drug: Clofarabine1 mg daily for 5 consecutive days followed by 23 days off drug |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Provide signed written informed consent.
- Patients with MDS must have IPSS score that falls in the intermediate or high risk disease (intermediate 1 will have to be transfusion dependent).
- Patients may have received up to two prior therapies for MDS including one hypomethylating agent and/or a biologic agent (biologic agents include GM-CSF or equivalent, danazol or equivalent, Sunitinib, Revlimid, ATG, or a vaccine).
- Age ≥ 18
- Have adequate renal and hepatic functions as indicated by the following laboratory values:
Key exclusion criteria (14 listed)
- 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.
- Active CNS disease
- 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.
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 |
|---|---|---|
| ClofarabineDose Escalation Schedule - Level 1: 1 mg daily x 5 days (orally) followed by 23 days off drug. Levels 2, 3, 4 and 5 are: 3, 5, 10 and 15 mg daily x 5 days followed by 23 days off drug. | Drug | Level 1 |
Primary outcome
To determine the safety, maximum tolerated dose (MTD) and recommended phase II dose of Clofarabine in patients with myelodysplastic syndrome (MDS).
Time frame: Up to 6 months
5 secondary outcomes
To determine the efficacy of Clofarabine in patients with MDS
Time frame: Up to 6 months
To determine the differences in clofarabine triphosphate levels in cells following clofarabine treatment
Time frame: Pre, Day 1: Hourly for 6 hours, Pre Day 5:Hourly for 5 hours
Determine the differences in clofarabine plasma levels following clofarabine treatment
Time frame: Pre, Day 1: Hourly for 6 hours, Pre Day 5:Hourly for 5 hours
Evaluate the effect of clofarabine on DNA methylation
Time frame: Pre and Day 1
Estimate post-treatment p53R2levels in patients treated at the MTD (in the expanded cohort)
Time frame: At 6 months
Results and safety
The study was stopped early (reason given: Drug provider withdrew support). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2016.
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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.
Wetzler Meir, MD principal investigator
Roswell Park Cancer Institute
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 Clofarabine in people with Myelodysplastic Syndrome, run by Roswell Park Cancer Institute 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 12 inclusion and 14 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 3 Jun 2016. 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: Drug provider withdrew support). 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?
To determine the safety, maximum tolerated dose (MTD) and recommended phase II dose of Clofarabine in patients with myelodysplastic syndrome (MDS). (time frame: Up to 6 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 3 Jun 2016.