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

NCT01813838 | Terminated Phase 1 DMC

• 1 other identifier: 2012-003120-21
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 17

Brief 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 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.

Conditions

SMD

Outcome Measures

Primary Outcomes (1)

• Determine the maximal tolerated dose (MTD)

  Phase I: Evaluation after 6 month of treatment. Responders will be treated until progression

  6 month of treatment

Study Arms (3)

ACADESINE 140mg/kg/d

EXPERIMENTAL

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

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

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

Drug: ACADESINE 315mg/kg/d

Interventions

ACADESINE 140mg/kg/d 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

Also known as: ACADESINE

ACADESINE 140mg/kg/d

ACADESINE 210mg/kg/d 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

Also known as: ACADESINE

ACADESINE 210mg/kg/d

ACADESINE 315mg/kg/d 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

Also known as: ACADESINE

ACADESINE 315mg/kg/d

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Groupe Francophone des Myelodysplasies: lead
• Advancell - Advanced In Vitro Cell Technologies, S.A.: collaborator

Study Sites (17)

Centre hospitalier de la côte Basque

Bayonne, 64100, France

Location

Hôpital Avicenne

Bobigny, 93009, France

Location

CHU de Haut-Lévèque

Bordeaux Pessac, 33604, France

Location

Centre henri Mondor

Créteil, 94010, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

CHU de Limoges

Limoges, 87042, France

Location

Institut paoli calmettes

Marseille, 13273, France

Location

centre hospitalier de Meaux

Meaux, 77100, France

Location

CHU de nantes

Nantes, 44093, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hôpital L'archet 1, Nice

Nice, 06202 cedex 3, France

Location

Hôpital Saint Louis

Paris, 75010, France

Location

Hôpital Saint Antoine

Paris, 75012, France

Location

Hôpital Saint-Louis

Paris, 75475 cedex 10, France

Location

Hôpital Cochin

Paris, 75679 cedex14, France

Location

Centre henri Becquerel

Rouen, 76038, France

Location

Hôpital Bretonneau de Tours

Tours, 37000, France

Location

MeSH Terms

Interventions

acadesine

Study Officials

• Thomas Cluzeau, MD

  Hôpital Saint Louis, Paris, France

  PRINCIPAL INVESTIGATOR

• Pierre Fenaux, MD

  Hôpital Saint Louis, Paris, France

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2013
• First Posted: March 19, 2013
• Study Start: June 1, 2013
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2015
• Last Updated: November 8, 2016

Record last verified: 2013-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (17)