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

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Assistance Publique - Hôpitaux de Paris
Information provided by:
Acute Leukemia French Association
ClinicalTrials.gov Identifier:
NCT01067274
First received: February 10, 2010
Last updated: January 7, 2011
Last verified: February 2010
History of Changes
  Purpose

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.


Condition Intervention Phase
Acute Myeloid Leukemia
 Drug: Vesanoid (ATRA)
Drug: AZACITIDINE (VIDAZA)
Drug: CYTARABINE
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Acute Leukemia French Association:

Primary Outcome Measures:
  • For randomization R1, the primary endpoint is Event-free Survival (EFS) [ Time Frame: 2-year EFS ] [ Designated as safety issue: No ]
  • For randomization R2, the primary endpoint is disease free survival (DFS) [ Time Frame: 2-year DFS ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete Response (CR) rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Response rate to azacitidine idarubicin +/-ATRA combination after intensive chemotherapy failure and identification of possible predictors of response to this therapy [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Assess the safety of combination ATRA + chemotherapy or idarubicin-azacitidine courses and of maintenance with azacitidine [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Effects on relapse rates of ATRA and maintenance, with respect to cytogenetics risk groups, subtypes of AML and mutational status (FLT3, MLL), and biomarkers [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 420
Study Start Date: April 2010
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: R1 Arm A : ATRA

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)
45 mg/m2/day in two divided doses from D8 to D28
Other Name: VEZANOIDE
No Intervention: R1 Arm B : no ATRA
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
Experimental: R2 Arm 1A : AZACITIDINE and ATRA
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)
45 mg/m2/day in two divided doses from D8 to D28
Other Name: VEZANOIDE
Drug: AZACITIDINE (VIDAZA)
75 mg/m2/12h SC from D1 to D5
Experimental: R2 Arm 1B : AZACITIDINE and No ATRA
Azacitidine: 75 mg/m2/12h SC from D1 to D5 Idarubicine: 9 mg/m2/d IV on D5
 Drug: AZACITIDINE (VIDAZA)
75 mg/m2/12h SC from D1 to D5
Experimental: R2 Arm 2A : ATRA
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)
45 mg/m2/day in two divided doses from D8 to D28
Other Name: VEZANOIDE
Drug: CYTARABINE
Cytarabine : 60 mg/m2/12h SC from D1 to D5
Experimental: R2 Arm 2B : no ATRA
Idarubicine : 9 mg/m2/d IV on D1 Cytarabine : 60 mg/m2/12h SC from D1 to D5
 Drug: CYTARABINE
Cytarabine : 60 mg/m2/12h SC from D1 to D5

Detailed Description:

Induction therapy :

First randomization (R1) at baseline : ATRA versus no ATRA.

Salvage therapy :

No conventional salvage therapy is planned. Patients who will not achieve CR, according to IWG criteria after induction will be treated with 3 courses of azacitidine and idarubicin +/- ATRA combination, if eligible for further treatment.

Followed by 3 identical courses and 6 courses of maintenance by azacitidine alone to be delivered every 28 days, in those patients reaching CR or PR after 3 courses (evaluation of response from 28 to 56 days from course 3).

Randomization R2: type of maintenance:

Response to induction will be evaluated 2 weeks after myeloid recovery, just before first consolidation course, due use of to pegfilgrastim, lenograstim or filgrastim during induction.

Responses will be classified according to the Revised Recommendations of the IWG for AML.

Patients in CR only will be subjected to a second randomization R2 as follows 6 courses of combined chemotherapy, will be delivered as outpatients, ATRA according to R1 randomization.

  Eligibility

Ages Eligible for Study:   65 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. APL in the WHO classification.
  2. Ph1-positive AML or prior Ph1-positive disease
  3. AML evolving from a prior MPN in the WHO 2008 classification.
  4. Prior treatment with chemotherapy or radiotherapy for another tumor
  5. Prior tumor, if not stable for at least two years, except in-situ carcinoma and skin carcinoma
  6. Prior advanced malignant hepatic tumor
  7. ECOG Performance Status Score > 2
  8. 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.
  9. Total serum bilirubin more than 2x's the ULN at the laboratory where the analysis was performed, except if AML-related.
  10. AST (SGOT) or ALT (SGPT) more than 2.5x's the ULN at the laboratory where the analysis was performed, except if AML-related
  11. LVEF less than.55 or equivalent by doppler echocardiography
  12. Known intolerance to Azacitidine, mannitol, retinoids
  13. Positive serum test for HIV and HTLV-1
  14. NYHA Grade 3/4 cardiac disease .
  15. Severe infection at inclusion time.
  16. Psychiatric disease or an history of non-compliance to medical regimens or patients considered potentially unreliable.
  17. Absence of health care insurance (affiliation à un régime de Sécurité Sociale)
  18. Participation to any study requiring informed consent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01067274

Locations
France
Chu Amiens Sud
Amiens, France, 80054
CH
Argenteuil, France, 95107
Hopital Avicenne
Bobigny, France
Chu Boulogne Sur Mer
Boulogne Sur Mer, France, 62321
CH
Caen, France, 14033
Hopital Percy
Clamart, France, 92141
Ch Sud Francilien
Corbeil Essonnes, France, 94010
Hopital Henri Mondor
Creteil, France
Ch Dunkerque
Dunkerque, France, 59385
CH
Lens, France, 62307
CHU
Lille, France, 59037
CH
Limoges, France, 87042
Hopital Edouard Herriot
Lyon, France
CH
Meaux, France, 77104
Centre Antoine Lacassagne
Nice, France, 06189
Hopital Pitie-Salpetriere
Paris, France, 75651
Hopital Saint-Louis
Paris, France
St Antoine Hospital
Paris, France, 75012
Necker Hospital
Paris 15, France, 75015
Ch Rene Dubos
Pontoise, France, 95303
CH
Roubaix, France, 59100
CHU
Rouen, France, 76038
CNLCC
Saint-Cloud, France, 92210
CH
Valenciennes, France, 59322
CH
Versailles, France
IGR
Villejuif, France
Sponsors and Collaborators
Acute Leukemia French Association
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: GARDIN CLAUDE, MD Acute Leukemia French Association
  More Information

No publications provided

Responsible Party: Dr Claude GARDIN, Avicenne Hospital- Hôpital Avicenne, AP-HP Bobigny
ClinicalTrials.gov Identifier: NCT01067274     History of Changes
Other Study ID Numbers: ALFA-0703 Study - P060205
Study First Received: February 10, 2010
Last Updated: January 7, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Acute Leukemia French Association:
Acute Myeloid Leukemia
Aged of 65 to 79 years
Older Patients with Acute Myeloblastic Leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Azacitidine
Cytarabine
Idarubicin
Tretinoin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
 Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Keratolytic Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on May 16, 2013