ALFA-0703 Study in Older Patients With Acute Myeloblastic Leukemia (AML)

NCT01067274 | Withdrawn Phase 3

• 1 other identifier: ALFA-0703 Study - P060205
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 26

Brief Summary

A Randomized Multicenter Phase III Study to Evaluate the Role of All-trans Retinoic Acid (ATRA) in Combination with Induction Chemotherapy, or Azacitidine and Idarubicin as salvage therapy and Idarubicin with Cytarabine or Azacitidine as Maintenance Therapy in Older Patients with Acute Myeloblastic Leukemia (AML). To compare the outcome of elderly patients with newly-diagnosed AML treated with standard induction chemotherapy and post-remission therapy, in only patients in CR, with either azacitidine or cytarabine combined to idarubicin +/- ATRA and salvage therapy with azacitidine combined to idarubicin +/- ATRA.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; Aged of 65 to 79 years; Older Patients with Acute Myeloblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• For randomization R1, the primary endpoint is Event-free Survival (EFS)

  2-year EFS

• For randomization R2, the primary endpoint is disease free survival (DFS)

  2-year DFS

Secondary Outcomes (5)

• Complete Response (CR) rate

  2 years

• Overall survival

  2 years

• Response rate to azacitidine idarubicin +/-ATRA combination after intensive chemotherapy failure and identification of possible predictors of response to this therapy

  2 years

• Assess the safety of combination ATRA + chemotherapy or idarubicin-azacitidine courses and of maintenance with azacitidine

  2 years

• Effects on relapse rates of ATRA and maintenance, with respect to cytogenetics risk groups, subtypes of AML and mutational status (FLT3, MLL), and biomarkers

  2 years

Study Arms (6)

R1 Arm A : ATRA

EXPERIMENTAL

Idarubicin: 9 mg/m2/d D1 to D4 Cytarabine : 200 mg/m2/d Continuous IV from D1 to D7 Peg-filgrastim : 6 mg SC D9 or filgrastim 5ug/kg/d SC or lenograstim 263ug/d IV 30mn, both from D9 to myeloid recovery(PMN \>1G/l over 2 days at minimum All-trans retinoic acid (ATRA): 45mg/m2/day in two divided doses from D8 to D28

Drug: Vesanoid (ATRA)

R1 Arm B : no ATRA

NO INTERVENTION

Idarubicin: 9 mg/m2/d D1 to D4 Cytarabine : 200 mg/m2/d Continuous IV from D1 to D7 Peg-filgrastim : 6 mg SC D9 or filgrastim 5ug/kg/d SC or lenograstim 263ug/d IV 30mn, both from D9 to myeloid recovery(PMN \>1G/l over 2 days at minimum

R2 Arm 1A : AZACITIDINE and ATRA

EXPERIMENTAL

Azacitidine: 75 mg/m2/12h SC from D1 to D5 Idarubicine: 9 mg/m2/d IV on D5 All-trans retinoic acid (ATRA): 45mg/m2/d in two divided doses from D8 to D21

Drug: Vesanoid (ATRA); Drug: AZACITIDINE (VIDAZA)

R2 Arm 1B : AZACITIDINE and No ATRA

EXPERIMENTAL

Azacitidine: 75 mg/m2/12h SC from D1 to D5 Idarubicine: 9 mg/m2/d IV on D5

Drug: AZACITIDINE (VIDAZA)

R2 Arm 2A : ATRA

EXPERIMENTAL

Idarubicine : 9 mg/m2/d IV on D1 Cytarabine : 60 mg/m2/12h SC from D1 to D5 All-trans retinoic acid (ATRA): 45mg/ m2/d in two divided doses from D8 to D21

Drug: Vesanoid (ATRA); Drug: CYTARABINE

R2 Arm 2B : no ATRA

EXPERIMENTAL

Idarubicine : 9 mg/m2/d IV on D1 Cytarabine : 60 mg/m2/12h SC from D1 to D5

Drug: CYTARABINE

Interventions

Vesanoid (ATRA) DRUG

45 mg/m2/day in two divided doses from D8 to D28

Also known as: VEZANOIDE

R1 Arm A : ATRA; R2 Arm 1A : AZACITIDINE and ATRA; R2 Arm 2A : ATRA

AZACITIDINE (VIDAZA) DRUG

75 mg/m2/12h SC from D1 to D5

R2 Arm 1A : AZACITIDINE and ATRA; R2 Arm 1B : AZACITIDINE and No ATRA

CYTARABINE DRUG

Cytarabine : 60 mg/m2/12h SC from D1 to D5

R2 Arm 2A : ATRA; R2 Arm 2B : no ATRA

Eligibility Criteria

• Age: 65 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Aged of 65 to 79 years
• With a morphologically proven diagnosis of AML according to WHO classification either de novo or AML with "myelodysplasia related changes"
• Not previously treated for AML
• Signed informed consent.

You may not qualify if:

• APL in the WHO classification.
• Ph1-positive AML or prior Ph1-positive disease
• AML evolving from a prior MPN in the WHO 2008 classification.
• Prior treatment with chemotherapy or radiotherapy for another tumor
• Prior tumor, if not stable for at least two years, except in-situ carcinoma and skin carcinoma
• Prior advanced malignant hepatic tumor
• ECOG Performance Status Score \> 2
• Creatinine level more than 2x's the upper limit of the normal range (ULN) at the laboratory where the analysis was performed, except if AML-related.
• Total serum bilirubin more than 2x's the ULN at the laboratory where the analysis was performed, except if AML-related.
• AST (SGOT) or ALT (SGPT) more than 2.5x's the ULN at the laboratory where the analysis was performed, except if AML-related
• LVEF less than.55 or equivalent by doppler echocardiography
• Known intolerance to Azacitidine, mannitol, retinoids
• Positive serum test for HIV and HTLV-1
• NYHA Grade 3/4 cardiac disease .
• Psychiatric disease or an history of non-compliance to medical regimens or patients considered potentially unreliable.

Sponsors & Collaborators

• Acute Leukemia French Association: lead
• Assistance Publique - Hôpitaux de Paris: collaborator

Study Sites (26)

Chu Amiens Sud

Amiens, 80054, France

Location

CH

Argenteuil, 95107, France

Location

Hopital Avicenne

Bobigny, France

Location

Chu Boulogne Sur Mer

Boulogne-sur-Mer, 62321, France

Location

CH

Caen, 14033, France

Location

Hopital Percy

Clamart, 92141, France

Location

Ch Sud Francilien

Corbeil-Essonnes, 94010, France

Location

Hopital Henri Mondor

Créteil, France

Location

Ch Dunkerque

Dunkirk, 59385, France

Location

CH

Lens, 62307, France

Location

CHU

Lille, 59037, France

Location

CH

Limoges, 87042, France

Location

Hopital Edouard Herriot

Lyon, France

Location

CH

Meaux, 77104, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

St Antoine Hospital

Paris, 75012, France

Location

Necker Hospital

Paris, 75015, France

Location

Hopital Pitie-Salpetriere

Paris, 75651, France

Location

Hopital Saint-Louis

Paris, France

Location

Ch Rene Dubos

Pontoise, 95303, France

Location

CH

Roubaix, 59100, France

Location

CHU

Rouen, 76038, France

Location

CNLCC

Saint-Cloud, 92210, France

Location

CH

Valenciennes, 59322, France

Location

CH

Versailles, France

Location

IGR

Villejuif, France

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Tretinoin; Azacitidine; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Arabinonucleosides

Study Officials

• GARDIN CLAUDE, MD

  Acute Leukemia French Association

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 10, 2010
• First Posted: February 11, 2010
• Study Start: April 1, 2010
• Primary Completion: April 1, 2016
• Last Updated: December 30, 2015

Record last verified: 2010-02

Locations

FR (26)