ALFA-0703 Study in Older Patients With Acute Myeloblastic Leukemia (AML)
Information source: Acute Leukemia French Association
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Acute Myeloid Leukemia
Intervention: Vesanoid (ATRA) (Drug); AZACITIDINE (VIDAZA) (Drug); CYTARABINE (Drug)
Phase: Phase 3
Status: Withdrawn
Sponsored by: Acute Leukemia French Association Official(s) and/or principal investigator(s): GARDIN CLAUDE, MD, Principal Investigator, Affiliation: Acute Leukemia French Association
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.
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: For randomization R1, the primary endpoint is Event-free Survival (EFS)For randomization R2, the primary endpoint is disease free survival (DFS)
Secondary outcome: Complete Response (CR) rateOverall survival Response rate to azacitidine idarubicin +/-ATRA combination after intensive chemotherapy failure and identification of possible predictors of response to this therapy Assess the safety of combination ATRA + chemotherapy or idarubicin-azacitidine courses and of maintenance with azacitidine Effects on relapse rates of ATRA and maintenance, with respect to cytogenetics risk groups, subtypes of AML and mutational status (FLT3, MLL), and biomarkers
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
Minimum age: 65 Years.
Maximum age: 79 Years.
Gender(s): Both.
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
Locations and Contacts
Chu Amiens Sud, Amiens 80054, France
CH, Argenteuil 95107, France
Hopital Avicenne, Bobigny, France
Chu Boulogne Sur Mer, Boulogne Sur Mer 62321, France
CH, Caen 14033, France
Hopital Percy, Clamart 92141, France
Ch Sud Francilien, Corbeil Essonnes 94010, France
Hopital Henri Mondor, Creteil, France
Ch Dunkerque, Dunkerque 59385, France
CH, Lens 62307, France
CHU, Lille 59037, France
CH, Limoges 87042, France
Hopital Edouard Herriot, Lyon, France
CH, Meaux 77104, France
Centre Antoine Lacassagne, Nice 06189, France
Necker Hospital, Paris 15 75015, France
Hopital Pitie-Salpetriere, Paris 75651, France
Hopital Saint-Louis, Paris, France
St Antoine Hospital, Paris 75012, France
Ch Rene Dubos, Pontoise 95303, France
CH, Roubaix 59100, France
CHU, Rouen 76038, France
CNLCC, Saint-Cloud 92210, France
CH, Valenciennes 59322, France
CH, Versailles, France
IGR, Villejuif, France
Additional Information
Starting date: April 2010
Last updated: January 7, 2011
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