GFM-Acadesine: A Phase I-II Trial of Acadesine

NCT ID: NCT01813838

Last Updated: 2016-11-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

5 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-06-30

Study Completion Date

2015-06-30

Brief Summary

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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

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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

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SMD

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ACADESINE 140mg/kg/d

3 patients will be included at the initial dose of Acadesine 140mg/kg/d

Group Type EXPERIMENTAL

ACADESINE 140mg/kg/d

Intervention Type DRUG

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/d

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

Group Type EXPERIMENTAL

ACADESINE 210mg/kg/d

Intervention Type DRUG

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/d

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

Group Type EXPERIMENTAL

ACADESINE 315mg/kg/d

Intervention Type DRUG

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

Interventions

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ACADESINE 140mg/kg/d

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

Intervention Type DRUG

ACADESINE 210mg/kg/d

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

Intervention Type DRUG

ACADESINE 315mg/kg/d

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

Intervention Type DRUG

Other Intervention Names

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ACADESINE ACADESINE ACADESINE

Eligibility Criteria

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Inclusion Criteria

* 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.
* 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.

Exclusion Criteria

* 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;
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Advancell - Advanced In Vitro Cell Technologies, S.A.

INDUSTRY

Sponsor Role collaborator

Groupe Francophone des Myelodysplasies

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas Cluzeau, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint Louis, Paris, France

Pierre Fenaux, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital Saint Louis, Paris, France

Locations

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Centre hospitalier de la côte Basque

Bayonne, , France

Site Status

Hôpital Avicenne

Bobigny, , France

Site Status

CHU de Haut-Lévèque

Bordeaux Pessac, , France

Site Status

Centre henri Mondor

Créteil, , France

Site Status

CHU de Grenoble

Grenoble, , France

Site Status

CHU de Limoges

Limoges, , France

Site Status

Institut paoli calmettes

Marseille, , France

Site Status

centre hospitalier de Meaux

Meaux, , France

Site Status

CHU de nantes

Nantes, , France

Site Status

Centre Antoine Lacassagne

Nice, , France

Site Status

Hôpital L'archet 1, Nice

Nice, , France

Site Status

Hôpital Saint Louis

Paris, , France

Site Status

Hôpital Saint Antoine

Paris, , France

Site Status

Hôpital Saint-Louis

Paris, , France

Site Status

Hôpital Cochin

Paris, , France

Site Status

Centre henri Becquerel

Rouen, , France

Site Status

Hôpital Bretonneau de Tours

Tours, , France

Site Status

Countries

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France

Other Identifiers

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2012-003120-21

Identifier Type: -

Identifier Source: org_study_id