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

Acute Myeloid Leukemia Clinical Trial

— ALFA-0703  

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)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01067274
• Other study ID #: ALFA-0703 Study - P060205
• Status: Withdrawn
• Phase: Phase 3
• First received: February 10, 2010
• Last updated: December 29, 2015
• Start date: April 2010

Study information

• Verified date: February 2010
• Source: Acute Leukemia French Association
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 65 Years to 79 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• Vesanoid (ATRA)
45 mg/m2/day in two divided doses from D8 to D28
• AZACITIDINE (VIDAZA)
75 mg/m2/12h SC from D1 to D5
• CYTARABINE
Cytarabine : 60 mg/m2/12h SC from D1 to D5

Locations

Country	Name	City	State
France	Chu Amiens Sud	Amiens
France	CH	Argenteuil
France	Hopital Avicenne	Bobigny
France	Chu Boulogne Sur Mer	Boulogne Sur Mer
France	CH	Caen
France	Hopital Percy	Clamart
France	Ch Sud Francilien	Corbeil Essonnes
France	Hopital Henri Mondor	Creteil
France	Ch Dunkerque	Dunkerque
France	CH	Lens
France	CHU	Lille
France	CH	Limoges
France	Hopital Edouard Herriot	Lyon
France	CH	Meaux
France	Centre Antoine Lacassagne	Nice
France	Hopital Pitie-Salpetriere	Paris
France	Hopital Saint-Louis	Paris
France	St Antoine Hospital	Paris
France	Necker Hospital	Paris 15
France	Ch Rene Dubos	Pontoise
France	CH	Roubaix
France	CHU	Rouen
France	CNLCC	Saint-Cloud
France	CH	Valenciennes
France	CH	Versailles
France	IGR	Villejuif

Sponsors (2)

Lead Sponsor	Collaborator
Acute Leukemia French Association	Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	For randomization R1, the primary endpoint is Event-free Survival (EFS)		2-year EFS	No
Primary	For randomization R2, the primary endpoint is disease free survival (DFS)		2-year DFS	No
Secondary	Complete Response (CR) rate		2 years	No
Secondary	Overall survival		2 years	No
Secondary	Response rate to azacitidine idarubicin +/-ATRA combination after intensive chemotherapy failure and identification of possible predictors of response to this therapy		2 years	No
Secondary	Assess the safety of combination ATRA + chemotherapy or idarubicin-azacitidine courses and of maintenance with azacitidine		2 years	No
Secondary	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	No