Clinical trial NCT01067274: ALFA-0703 Study in Older Patients With Acute Myeloblastic Leukemia (AML)
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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Acute Myeloid Leukemia
Keywords: Acute Myeloid Leukemia
Aged of 65 to 79 years
Older Patients with Acute Myeloblastic Leukemia
Lead sponsor: Acute Leukemia French Association
Sponsor class: OTHER
Collaborators: name: Assistance Publique - Hôpitaux de Paris
First posted: 2010-02-11
Enrollment: 0
Sex: ALL
Minimum age (years): 65
Maximum age (years): 79
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: For randomization R1, the primary endpoint is Event-free Survival (EFS)
timeFrame: 2-year EFS
measure: For randomization R2, the primary endpoint is disease free survival (DFS)
timeFrame: 2-year DFS
Secondary outcomes:
measure: Complete Response (CR) rate
timeFrame: 2 years
measure: Overall survival
timeFrame: 2 years
measure: Response rate to azacitidine idarubicin +/-ATRA combination after intensive chemotherapy failure and identification of possible predictors of response to this therapy
timeFrame: 2 years
measure: Assess the safety of combination ATRA + chemotherapy or idarubicin-azacitidine courses and of maintenance with azacitidine
timeFrame: 2 years
measure: Effects on relapse rates of ATRA and maintenance, with respect to cytogenetics risk groups, subtypes of AML and mutational status (FLT3, MLL), and biomarkers
timeFrame: 2 years
Other outcomes:
Locations:
city: Amiens
country: France
facility: Chu Amiens Sud
city: Argenteuil
country: France
facility: CH
city: Bobigny
country: France
facility: Hopital Avicenne
city: Boulogne Sur Mer
country: France
facility: Chu Boulogne Sur Mer
city: Caen
country: France
facility: CH
city: Clamart
country: France
facility: Hopital Percy
city: Corbeil Essonnes
country: France
facility: Ch Sud Francilien
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Dunkerque
country: France
facility: Ch Dunkerque
city: Lens
country: France
facility: CH
city: Lille
country: France
facility: CHU
city: Limoges
country: France
facility: CH
city: Lyon
country: France
facility: Hopital Edouard Herriot
city: Meaux
country: France
facility: CH
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris 15
country: France
facility: Necker Hospital
city: Paris
country: France
facility: St Antoine Hospital
city: Paris
country: France
facility: Hopital Pitie-Salpetriere
city: Paris
country: France
facility: Hopital Saint-Louis
city: Pontoise
country: France
facility: Ch Rene Dubos
city: Roubaix
country: France
facility: CH
city: Rouen
country: France
facility: CHU
city: Saint-Cloud
country: France
facility: CNLCC
city: Valenciennes
country: France
facility: CH
city: Versailles
country: France
facility: CH
city: Villejuif
country: France
facility: IGR
Study officials:
affiliation: Acute Leukemia French Association
name: GARDIN CLAUDE, MD
role: PRINCIPAL_INVESTIGATOR
References: