SMDPhase 1/2AcadesineNCT01813838
GFM-Acadesine: A Phase I-II Trial of Acadesine
A Phase 1/2 study testing ACADESINE 140mg/kg/d, ACADESINE 210mg/kg/d and ACADESINE 315mg/kg/d in people with SMD, run by Groupe Francophone des Myelodysplasies at 17 sites in France.
Trial summary
A phase I-II trial of Acadesine in IPSS high and int 2 myelodysplastic syndromes, acute myeloid leukemia with 20-30% marrow blasts and chronic myelomonocytic leukemia type 2 not responding to Azacitidine or Decitabine for at least 6 courses or relapsing after a response: Patients will receive 6 treatment cycles unless… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- SMD
- What is being tested?
- ACADESINE 140mg/kg/d, ACADESINE 210mg/kg/d and ACADESINE 315mg/kg/d
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 17 sitesFrance
- Study dates
- Jun 2013to Jun 2015
- 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
- Myelodysplastic syndrome including the following WHO categories: refractory anemia with excess blasts (RAEB), non-proliferative chronic myelomonocytic leukemia (CMML) (leukocytes < 13 G/L but > 10% marrow blasts), WHO- AML with 20-30% marrow blasts (RAEB-T according to the FAB classification)
- Prior treatment with Azacitidine or Decitabine for at least 6 courses without response (including CR, PR, marrow CR and stable disease with hematological improvement) or relapse after a response
- IPSS score >1 (IPSS: Int-2 or High);
- Age ≥ 18 years;
- Normal liver function tests, defined by total bilirubin and transaminases less than 1.5 time the upper limit of normal;
- Normal renal function, defined by creatinine less than 1.5 time the upper limit of normal, creatinine clearance ≥ 50 mL/min.
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- Patient ineligible for allogeneic hematopoietic stem cell transplantation;
- Written informed consent;
- Patient must understand and voluntarily sign consent form;
- Patient must be able to adhere to the visit schedule as outlined in the study and follow protocol requirements;
- ECOG performance status between 0-2 at the time of screening;
- Women of childbearing potential must:
- Agree to use effective contraception without interruption throughout the study and for a further 1 month after the end of treatment;
- Men must:
- Agree to not conceive during the treatment and to use effective contraception during the treatment period (including periods of dose reduction or temporary suspension) and for a further 1 month after the end of treatment if their partner is of childbearing potential.
Who cannot join
- Severe infection or any other uncontrolled severe condition
- Significant cardiac disease - NYHA Class III or IV or having suffered a myocardial infarction in the last 6 months
- Less than 30 days since prior treatment with growth factors (EPO, G-CSF)
- 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.
- Active cancer, or cancer during the year prior to trial entry other than basal cell carcinoma or carcinoma in situ of the cervix or breast;
- Patient already enrolled in another therapeutic trial of an investigational drug;
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- HIV infection or active hepatitis B or C;
- Women who are or could become pregnant or who are currently breastfeeding;
- Any medical or psychiatric contraindication that would prevent the patient from understanding and signing the informed consent form;
- Patient eligible for allotransplantation.
- Known allergy to acadesine or any of its excipients
- No affiliation to an insurance system
Trial locations and contacts
17 sites in 1 country.
17 sites in 1 country
France17 sites
Centre hospitalier de la côte Basque
Bayonne, 64100
Hôpital Avicenne
Bobigny, 93009
CHU de Haut-Lévèque
Bordeaux Pessac, 33604
Centre henri Mondor
Créteil, 94010
CHU de Grenoble
Grenoble, 38043
CHU de Limoges
Limoges, 87042
Institut paoli calmettes
Marseille, 13273
centre hospitalier de Meaux
Meaux, 77100
CHU de nantes
Nantes, 44093
Centre Antoine Lacassagne
Nice, 06189
Hôpital L'archet 1, Nice
Nice, 06202 cedex 3
Hôpital Saint Louis
Paris, 75010
Hôpital Saint Antoine
Paris, 75012
Hôpital Saint-Louis
Paris, 75475 cedex 10
Hôpital Cochin
Paris, 75679 cedex14
Centre henri Becquerel
Rouen, 76038
Hôpital Bretonneau de Tours
Tours, 37000
About this study
Official title: A Phase I-II Trial of Acadesine in IPSS High and Int-2 SMD, LAM With 20-30% Marrow Blasts and CMML Type 2 Not Responding to Azacitidine or Decitabine for at Least 6 Courses or Relapsing After a Response
A phase I-II trial of Acadesine in IPSS high and int 2 myelodysplastic syndromes, acute myeloid leukemia with 20-30% marrow blasts and chronic myelomonocytic leukemia type 2 not responding to Azacitidine or Decitabine for at least 6 courses or relapsing after a response:
Patients will receive 6 treatment cycles unless disease progression, transformation, or unacceptable toxicity occurs, or the patient refuses to continue participating in the study.
Efficacy will be assessed at the end of the 2nd, 4th and 6th cycles. After 6 cycles, patients demonstrating a response (CR, PR, marrow CR, or HI) will be able to continue with cycles of Acadesine (at the same dose as in the preceding cycles, depending on their cohort) until progression.
Read the detailed description
Primary objectives
Phase I:
To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of increasing doses of IV Acadesine administered on D1, D3, D5, D8, D10 and D12 of 28 to 56 day-courses
Phase II:
To confirm safety and hematological toxicity in 18 additional patients
Secondary objectives:
Phase I:
- To determine response rates, as defined by the 2006 modified IWG criteria,
- 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.
Phase II:
To determine
- response rate as defined by the 2006 modified IWG criteria
- toxicity profile and safety
- response duration
- rate of progression to AML
- overall survival
- Conditions
- SMD
- Being tested
- ACADESINE 140mg/kg/d, ACADESINE 210mg/kg/d, ACADESINE 315mg/kg/d
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ACADESINE 140mg/kg/dDrug
Also called ACADESINE
3 patients will be included at the initial dose of 140mg/kg/d. In absence of toxicity, 3 additional patients will be included at the higher dosage.
In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 140mg/kg/d.
In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 85mg/kg/d
ACADESINE 210mg/kg/dDrug
Also called ACADESINE
3 patients will be included at the dose of 210mg/kg/d. In absence of toxicity, 3 additional patients will be included at the higher dosage.
In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 210mg/kg/d.
In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 140mg/kg/d
ACADESINE 315mg/kg/dDrug
Also called ACADESINE
3 patients will be included at the dose of 315mg/kg/d.
In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 315mg/kg/d.
In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 210mg/kg/d
| Study group | Role | What they receive |
|---|---|---|
| ACADESINE 140mg/kg/d | Experimental | 3 patients will be included at the initial dose of Acadesine 140mg/kg/d Receives: Drug: ACADESINE 140mg/kg/d |
| ACADESINE 210mg/kg/d | Experimental | In absence of toxicity at the dose of 140mg/kg/d. There is a dose escalation of acadesine at the dose of 210mg/kg/d for 3 additionnal patients Receives: Drug: ACADESINE 210mg/kg/d |
| ACADESINE 315mg/kg/d | Experimental | In absence of toxicity at the dose of 210mg/kg/d. There is a dose escalation of acadesine at the dose of 315mg/kg/d for 3 additionnal patients Receives: Drug: ACADESINE 315mg/kg/d |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the maximal tolerated dose (MTD)
Phase I: Evaluation after 6 month of treatment. Responders will be treated until progression
Measured: 6 month of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2013 (estimated)
- Study startJun 2013
- Primary completionJun 2013
- Study completionJun 2015
Why it stopped: Renal toxicity
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SMDStudies 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
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Groupe Francophone des Myelodysplasies
- Sponsor type
- University, hospital or other
- Collaborators
- Advancell - Advanced In Vitro Cell Technologies, S.A.
- Responsible party
- Sponsor
- Investigators
- Thomas Cluzeau, MD, Principal investigator, Hôpital Saint Louis, Paris, FrancePierre Fenaux, MD, Principal investigator, Hôpital Saint Louis, Paris, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01813838
- Sponsor's protocol ID
- 2012-003120-21
- Acronym
- Acadesine
- Status last verified
- Aug 2013
- First submitted
- 14 Mar 2013
- Last updated
- 8 Nov 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-II Trial of Acadesine in IPSS High and Int-2 SMD, LAM With 20-30% Marrow Blasts and CMML Type 2 Not Responding to Azacitidine or Decitabine for at Least 6 Courses or Relapsing After a Response
- ClinicalTrials.gov ID
- NCT01813838
- Acronym / sponsor ID
- Acadesine / 2012-003120-21
- Conditions
- SMD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Renal toxicity
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Groupe Francophone des MyelodysplasiesUniversity, hospital or other
- Collaborators
- Advancell - Advanced In Vitro Cell Technologies, S.A.
- Study start
- Jun 2013
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 19 Mar 2013 (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.
A phase I-II trial of Acadesine in IPSS high and int 2 myelodysplastic syndromes, acute myeloid leukemia with 20-30% marrow blasts and chronic myelomonocytic leukemia type 2 not responding to Azacitidine or Decitabine for at least 6 courses or relapsing after a response:
Patients will receive 6 treatment cycles unless disease progression, transformation, or unacceptable toxicity occurs, or the patient refuses to continue participating in the study.
Efficacy will be assessed at the end of the 2nd, 4th and 6th cycles. After 6 cycles, patients demonstrating a response (CR, PR, marrow CR, or HI) will be able to continue with cycles of Acadesine (at the same dose as in the preceding cycles, depending on their cohort) until progression.
Detailed description
Primary objectives
Phase I:
To determine the maximal tolerated dose (MTD) and dose limiting toxicities (DLTs) of increasing doses of IV Acadesine administered on D1, D3, D5, D8, D10 and D12 of 28 to 56 day-courses
Phase II:
To confirm safety and hematological toxicity in 18 additional patients
Secondary objectives:
Phase I:
- To determine response rates, as defined by the 2006 modified IWG criteria,
- 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.
Phase II:
To determine
- response rate as defined by the 2006 modified IWG criteria
- toxicity profile and safety
- response duration
- rate of progression to AML
- overall survival
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ACADESINE 140mg/kg/d | Experimental | Drug: ACADESINE 140mg/kg/d3 patients will be included at the initial dose of Acadesine 140mg/kg/d |
| ACADESINE 210mg/kg/d | Experimental | Drug: ACADESINE 210mg/kg/dIn absence of toxicity at the dose of 140mg/kg/d. There is a dose escalation of acadesine at the dose of 210mg/kg/d for 3 additionnal patients |
| ACADESINE 315mg/kg/d | Experimental | Drug: ACADESINE 315mg/kg/dIn absence of toxicity at the dose of 210mg/kg/d. There is a dose escalation of acadesine at the dose of 315mg/kg/d for 3 additionnal patients |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Myelodysplastic syndrome including the following WHO categories: refractory anemia with excess blasts (RAEB), non-proliferative chronic myelomonocytic leukemia (CMML) (leukocytes < 13 G/L but > 10% marrow blasts), WHO- AML with 20-30% marrow blasts (RAEB-T according to the FAB classification)
- Prior treatment with Azacitidine or Decitabine for at least 6 courses without response (including CR, PR, marrow CR and stable disease with hematological improvement) or relapse after a response
- IPSS score >1 (IPSS: Int-2 or High);
- Age ≥ 18 years;
- Normal liver function tests, defined by total bilirubin and transaminases less than 1.5 time the upper limit of normal;
Key exclusion criteria (12 listed)
- Severe infection or any other uncontrolled severe condition
- Significant cardiac disease - NYHA Class III or IV or having suffered a myocardial infarction in the last 6 months
- Less than 30 days since prior treatment with growth factors (EPO, G-CSF)
- 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.
- Active cancer, or cancer during the year prior to trial entry other than basal cell carcinoma or carcinoma in situ of the cervix or breast;
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 |
|---|---|---|
| ACADESINE 140mg/kg/dAlso: ACADESINE3 patients will be included at the initial dose of 140mg/kg/d. In absence of toxicity, 3 additional patients will be included at the higher dosage. In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 140mg/kg/d. In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 85mg/kg/d | Drug | ACADESINE 140mg/kg/d |
| ACADESINE 210mg/kg/dAlso: ACADESINE3 patients will be included at the dose of 210mg/kg/d. In absence of toxicity, 3 additional patients will be included at the higher dosage. In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 210mg/kg/d. In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 140mg/kg/d | Drug | ACADESINE 210mg/kg/d |
| ACADESINE 315mg/kg/dAlso: ACADESINE3 patients will be included at the dose of 315mg/kg/d. In case of 1/3 toxicity, 3 additionnal patients will be included at the same dose level, currently 315mg/kg/d. In case of toxicity in 2 or more patients, the dose of acadesine will be reduced at the the dose of 210mg/kg/d | Drug | ACADESINE 315mg/kg/d |
Primary outcome
Determine the maximal tolerated dose (MTD)
Time frame: 6 month of treatment
Phase I: Evaluation after 6 month of treatment. Responders will be treated until progression
Results and safety
The study was stopped early (reason given: Renal toxicity). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2016.
- Individual participant dataSharing planned: No
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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.
Thomas Cluzeau, MD principal investigator
Hôpital Saint Louis, Paris, France
Pierre Fenaux, MD principal investigator
Hôpital Saint Louis, Paris, France
17 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 ACADESINE 140mg/kg/d, ACADESINE 210mg/kg/d and ACADESINE 315mg/kg/d in people with SMD, run by Groupe Francophone des Myelodysplasies at 17 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 15 inclusion and 12 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 8 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 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 was stopped early (reason given: Renal toxicity). 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?
Determine the maximal tolerated dose (MTD) (time frame: 6 month of treatment). 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 8 Nov 2016.