Myelodysplastic SyndromePhase 1/2NCT01063257
Clofarabine in High Risk Myelodysplastic Syndrome (MDS)
A Phase 1/2 study testing Clofarabine in people with Myelodysplastic Syndrome, run by Groupe Francophone des Myelodysplasies at 5 sites in France.
Trial summary
This study aims to determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of low dose IV clofarabine for MDS patients after treatment failure of azacitidine. 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
- 76 participants
- Where
- 5 sitesFrance
- Study dates
- Apr 2010to Mar 2014
- Phase
- Phase 1/2
- 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
- Patients aged 18 years or more with MDS according to FAB classification and intermediate-2 or high IPSS risk scores, or CMML (with WBC < 13 x 109/L and bone marrow blasts > 10 %) according to WHO classification, or AML according to WHO classification if less than 30 % bone marrow blasts (RAEB-T according to FAB MDS classification or AML according to WHO classification with more than 30 % with bone marrow blasts only if preceded by a proven MDS phase.
- Patients previously treated by azacitidine (Vidaza®) in proven progression, or stable after 6 courses with ongoing transfusion dependent anemia (> 4 RBC units in the 8 weeks preceding inclusion (as erythroid response in IWG 2006 criteria is reduction of at least 4 RBC units in 8 weeks).
- Previous biological and or targeted therapies of MDS or AML are allowed if stopped more than 1 month before inclusion.
- ECOG PS ≤ 2.
- Adequate renal and liver function :
- i.e. Serum creatinine < 110 microM in men or 90 microM in women. If plasma creatinine level < 90 - 110 microM, 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 (MDRD) equation where Predicted GFR (mL/min/1.73 m2) = 32788 x (plasma creatinine level (microM)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is African American)
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- Bilirubin < 1.5 x ULN, (except increased unconjugated bilirubin due to dyserythropoiesis).
- Aspartate transaminase (AST)/alanine transaminase (ALT) < 2.5 × ULN and Alkaline phosphatase < 2.5 × ULN.
- Absence of pregnancy or lactation in female patients (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.
- Provided signed written informed consent.
- Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
Who cannot join
- Patients with AML and bone marrow blasts count of 20-30%, if candidates to intensive AML type chemotherapy.
- Known hypersensitivity to clofarabine or excipients.
- Concomitant malignant disease.
- Active uncontrolled infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
- Concomitant severe cardiovascular disease, i.e. congestive heart failure (NYHA grade > 3).
- 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.
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- No affiliation to a national insurance scheme directly or to an equivalent system.
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
France5 sites
Hôpital Avicenne
Bobigny, 93009
Institut Paoli-Calmettes
Marseille, 13009
Hôpital Saint-Louis
Paris, 75475
Hopital Cochin Service d'Hématologie
Paris, 75679
Centre Henri Becquerel
Rouen, 76038
About this study
Official title: A Phase I/II Multicenter Study of IV Clofarabine in Patients With High-Risk Myelodysplastic Syndrome Who Have Failed Therapy With Azacitidine: the NIDEVOL Study
This study aims to determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of low dose IV clofarabine for MDS patients after treatment failure of azacitidine.
Read the detailed description
The study is an open-label, 3+3 dose-escalation, phase I/II study.The duration of enrollment in the phase I study is 12 months.
Fourteen patients will be enrolled at the RD using the selected dosing in each cohort, for an enrollment period of 12 months.
Each patient may receive up to 8 courses, every 4 to 8 weeks in a D1-D5 schedule or every other day from D1 to D10.
Each patient will be followed for up to 24 months.
Primary endpoint of the phase I part:
- To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of increased doses of IV clofarabine administered either daily from D1 to D5 for a 28 to 56 day-course or every other day from D1 to D10 for a 28 to 56 day-course.
Secondary endpoints:
- To determine response rates, as defined by the 2006 modified IWG criteria, associated with the two different dosing and scheduling of clofarabine in patients with high-risk MDS or AML patients with less than 30% marrow blasts (RAEB-T in FAB MDS classification), previously treated by azacitidine and without erythroid response after 6 cycles of azacitidine.
- To evaluate response duration, time to IPSS progression, and loss of RBC transfusion independence in these patients.
- To evaluate hospitalization duration, rates of rehospitalization for non-hematological toxicities, severe bleeding or febrile neutropenia.
If treatment is feasible the study will be extended to the phase II part.
Study Objectives:
Primary endpoint:
- To confirm safety and hematological toxicity in 14 additional patients. Secondary endpoints
- To evaluate response duration, time to IPSS progression, and loss of RBC transfusion independence in these patients.
- To evaluate hospitalization duration, rates of rehospitalization for non hematological toxicities, severe bleeding or febrile neutropenia.
- To determine the response rate as defined by the 2006 modified IWG criteria.
- Conditions
- Myelodysplastic Syndrome
- Being tested
- Clofarabine
- Keywords
- 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
Also called EVOLTRA®
The dosage of Clofarabine will be gradually augmented in a 3+3 design for each following dose level:
DL1 - 5mg/m2/d, DL2 - 7.5mg/m2/d, DL3 - 10mg/m2/d, DL4 - 12.5mg/m2/d (This dose may not be reached and is an optional dose level in case the MTD is not reached before and depending on further data from the ongoing MDS Phase IIa oral formulation trial).
The DLa will be the following:
DL1a - 2.5mg/m2/d, DL2a - 6.5mg/m2/d, DL3a - 8.5mg/m2/d, DL4a - 11.5mg/m2/d (In case of activation of the DL4 step). Dose levels 1a, 2a and 3a will be used for de-escalation.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | Clofarabine treatment at D1-D5 Receives: Drug: Clofarabine |
| Cohort B | Experimental | Clofarabine treatment at D1, D3, D5, D8, D10 Receives: Drug: Clofarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs)
After one course treatment.
Measured: 1-2 months
Secondary outcomes (5)
To determine response rates.
After one, two and eight courses of treatment.
Measured: 1-16 months.
To evaluate the response duration.
After one, two and eight courses of treatment.
Measured: 1-16 months
To evaluate time to IPSS progression.
After one, two and eight courses of treatment.
Measured: 1-16 months
To evaluate loss of RBC transfusion independence and hospitalization duration.
After one, two and eight courses of treatment.
Measured: 1-16 months
To evaluate rates of rehospitalization for non-hematological toxicities, severe bleeding or febrile neutropenia.
After one, two and eight courses of treatment.
Measured: 1-16 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2010 (estimated)
- Study startApr 2010
- Primary completionMar 2014
- Study completionMar 2014
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.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Groupe Francophone des Myelodysplasies
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Sponsor
- Investigators
- Thorsten Braun, MD, Principal investigator, Groupe Francophone des MyélodysplasiesClaude Gardin, MD, Study chair, Groupe Francophone des Myélodysplasies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01063257
- Sponsor's protocol ID
- GFM-CLO-08
- Status last verified
- Mar 2013
- First submitted
- 3 Feb 2010
- Last updated
- 19 Mar 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Multicenter Study of IV Clofarabine in Patients With High-Risk Myelodysplastic Syndrome Who Have Failed Therapy With Azacitidine: the NIDEVOL Study
- ClinicalTrials.gov ID
- NCT01063257
- Acronym / sponsor ID
- GFM-CLO-08
- Conditions
- Myelodysplastic Syndrome
- Keywords
- Myelodysplastic Syndrome
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Groupe Francophone des MyelodysplasiesUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- Apr 2010
- Primary completion
- Mar 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 5 Feb 2010 (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 study aims to determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of low dose IV clofarabine for MDS patients after treatment failure of azacitidine.
Detailed description
The study is an open-label, 3+3 dose-escalation, phase I/II study.The duration of enrollment in the phase I study is 12 months.
Fourteen patients will be enrolled at the RD using the selected dosing in each cohort, for an enrollment period of 12 months.
Each patient may receive up to 8 courses, every 4 to 8 weeks in a D1-D5 schedule or every other day from D1 to D10.
Each patient will be followed for up to 24 months.
Primary endpoint of the phase I part:
- To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of increased doses of IV clofarabine administered either daily from D1 to D5 for a 28 to 56 day-course or every other day from D1 to D10 for a 28 to 56 day-course.
Secondary endpoints:
- To determine response rates, as defined by the 2006 modified IWG criteria, associated with the two different dosing and scheduling of clofarabine in patients with high-risk MDS or AML patients with less than 30% marrow blasts (RAEB-T in FAB MDS classification), previously treated by azacitidine and without erythroid response after 6 cycles of azacitidine.
- To evaluate response duration, time to IPSS progression, and loss of RBC transfusion independence in these patients.
- To evaluate hospitalization duration, rates of rehospitalization for non-hematological toxicities, severe bleeding or febrile neutropenia.
If treatment is feasible the study will be extended to the phase II part.
Study Objectives:
Primary endpoint:
- To confirm safety and hematological toxicity in 14 additional patients. Secondary endpoints
- To evaluate response duration, time to IPSS progression, and loss of RBC transfusion independence in these patients.
- To evaluate hospitalization duration, rates of rehospitalization for non hematological toxicities, severe bleeding or febrile neutropenia.
- To determine the response rate as defined by the 2006 modified IWG criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Drug: ClofarabineClofarabine treatment at D1-D5 |
| Cohort B | Experimental | Drug: ClofarabineClofarabine treatment at D1, D3, D5, D8, D10 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients aged 18 years or more with MDS according to FAB classification and intermediate-2 or high IPSS risk scores, or CMML (with WBC < 13 x 109/L and bone marrow blasts > 10 %) according to WHO classification, or AML according to WHO classification if less than 30 % bone marrow blasts (RAEB-T according to FAB MDS classification or AML according to WHO classification with more than 30 % with bone marrow blasts only if preceded by a proven MDS phase.
- Patients previously treated by azacitidine (Vidaza®) in proven progression, or stable after 6 courses with ongoing transfusion dependent anemia (> 4 RBC units in the 8 weeks preceding inclusion (as erythroid response in IWG 2006 criteria is reduction of at least 4 RBC units in 8 weeks).
- Previous biological and or targeted therapies of MDS or AML are allowed if stopped more than 1 month before inclusion.
- ECOG PS ≤ 2.
- Adequate renal and liver function :
Key exclusion criteria (9 listed)
- Patients with AML and bone marrow blasts count of 20-30%, if candidates to intensive AML type chemotherapy.
- Known hypersensitivity to clofarabine or excipients.
- Concomitant malignant disease.
- Active uncontrolled infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
- Concomitant severe cardiovascular disease, i.e. congestive heart failure (NYHA grade > 3).
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: EVOLTRA®The dosage of Clofarabine will be gradually augmented in a 3+3 design for each following dose level: DL1 - 5mg/m2/d, DL2 - 7.5mg/m2/d, DL3 - 10mg/m2/d, DL4 - 12.5mg/m2/d (This dose may not be reached and is an optional dose level in case the MTD is not reached before and depending on further data from the ongoing MDS Phase IIa oral formulation trial). The DLa will be the following: DL1a - 2.5mg/m2/d, DL2a - 6.5mg/m2/d, DL3a - 8.5mg/m2/d, DL4a - 11.5mg/m2/d (In case of activation of the DL4 step). Dose levels 1a, 2a and 3a will be used for de-escalation. | Drug | Cohort A, Cohort B |
Primary outcome
To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs)
Time frame: 1-2 months
After one course treatment.
5 secondary outcomes
To determine response rates.
Time frame: 1-16 months.
To evaluate the response duration.
Time frame: 1-16 months
To evaluate time to IPSS progression.
Time frame: 1-16 months
To evaluate loss of RBC transfusion independence and hospitalization duration.
Time frame: 1-16 months
To evaluate rates of rehospitalization for non-hematological toxicities, severe bleeding or febrile neutropenia.
Time frame: 1-16 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2014.
- Website of the Groupe Francophone des Myélodysplasies (GFM)Link 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.
Thorsten Braun, MD principal investigator
Groupe Francophone des Myélodysplasies
Claude Gardin, MD study chair
Groupe Francophone des Myélodysplasies
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Clofarabine in people with Myelodysplastic Syndrome, run by Groupe Francophone des Myelodysplasies at 5 sites in France.
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 9 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 19 Mar 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France. 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 combined 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.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) (time frame: 1-2 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 19 Mar 2014.