Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Dexamethasone Added to Intensive Chemotherapy in Older Patients With Acute Myeloid Leukemia (AML) (DEXAML-02)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03609060
Recruitment Status : Recruiting
First Posted : August 1, 2018
Last Update Posted : October 24, 2018
Sponsor:
Information provided by (Responsible Party):
French Innovative Leukemia Organisation

Brief Summary:
Recent preclinical and clinical data strongly suggested that dexamethasone could improve the activity of intensive chemotherapy in AML. In this study, the FILO study group will assess the impact of adding dexamethasone to both induction and consolidation therapy in older AML patients with intermediate or favorable risk.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Dexamethasone Phase 2

Detailed Description:

Patients will receive dexamethasone in addition to induction and post-remission chemotherapy

The principal objective of the study is to determine whether adding dexamethasone to induction and post-remission therapy results in significant improvement of event-free survival (EFS) as compared with an historical cohort of the FILO LAM-SA 2007 trial.

Induction therapy: Idarabucin + Cyrarabine + Lomustine (ICL) + Dexamethasone. Idarubicin 8 mg/m²/day, IV over 15 minutes, D1 to D5; Cytarabine 100 mg/m²/d, IV continuous 24h-infusion D1 to D7; Lomustine 200 mg/m²/d, orally at D1; Dexamethasone 10 mg/12h, IV over 30 minutes, D1 to D3.

Post remission therapy: Idarabucin + Cyrarabine (IC) + Dexamethasone

Idarubicin 8 mg/m², IV over 15 minutes, D1; Cytarabine 50 mg/m²/12h, subcutaneous, D1 to D5; Dexamethasone 20 mg/d, IV over 30 minutes, D1.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Dexamethasone Added to Induction and Post-remission Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)
Actual Study Start Date : August 24, 2018
Estimated Primary Completion Date : August 31, 2025
Estimated Study Completion Date : December 31, 2025


Arm Intervention/treatment
Experimental: DEXAML

Induction therapy:

Idarubicin 8 mg/m²/day, IV over 15 minutes, D1 to D5 + Cytarabine 100 mg/m²/d, IV continuous 24h-infusion D1 to D7 + Lomustine 200 mg/m²/d, orally at D1 + Dexamethasone 10 mg/12h, IV over 30 minutes, D1 to D3. Addition of midostaurin in patients with Fms-like tyrosine kinase 3-internal tandem ( FLT3-ITD) or Fms-like tyrosine kinase 3-tyrosine kinase domain (FLT3-TKD) mutations is allowed.

Post remission therapy:

Idarubicin 8 mg/m², IV over 15 minutes, D1 + Cytarabine 50 mg/m²/12h, subcutaneous, D1 to D5 + Dexamethasone 20 mg/d, IV over 30 minutes, D1. Addition of midostaurin in patients with FLT3-ITD or FLT3-TKD mutations is allowed. Intermediate dose cytarabine is allowed for patients with Core Binding Factor AML (CBF-AML).

Allogeneic stem-cell transplantation allowed after 2 to 4 cycles

Drug: Dexamethasone
Dexamethasone 10 mg/12h, IV over 30 minutes, D1 to D3 concomitant to induction and post remission chemotherapy in elderly patients with AML Induction




Primary Outcome Measures :
  1. Event Free survival (EFS) [ Time Frame: Within 2 years after the start of the Treatement ]
    Time from the date of induction start to the date of induction failure, relapse from CR or CRi, or death from any cause, whichever occurs first. CR, CRi, relapse from CR or CRi and induction failure are defined according to the ELN 2017 recommendations


Secondary Outcome Measures :
  1. Treatment response [ Time Frame: Up to 45 day ]
    Response to therapy after induction therapy defined as CR or CRi according to the 2017 European Leukemia Net (ELN) recommendations.

  2. Minimal Residual Disease (MRD) [ Time Frame: Up to day 45 after induction chemotherapy, second and last consolidation cycle. ]
    Presence of MRD after induction therapy and after post-remission therapy, measured by either quantitative PCR or flow cytometry

  3. Allogenic Stem Cells Transplantation (ASCT) [ Time Frame: Up to one year ]
    Number of patients with ASCT

  4. Remission duration (relapse from CR or CRi) [ Time Frame: two years ]
    Time from the date of CR or CRi to the date of relapse according to the 2017 ELN recommendations

  5. Relapse Free Survival (RFS) [ Time Frame: two years ]
    Time from the date of CR or CRi to the date of relapse or death from any cause, whichever occurs first, according to the ELN 2017 recommendations

  6. Overall Survival (OS) [ Time Frame: two years ]
    Time from the date of randomization to the date of death from any cause

  7. Adverse events [ Time Frame: up to 60 months ]
    Incidence and severity of Adverse Events according to the descriptions and grading scale found in the National Cancer Institute - Common Terminology Criteria (NCI-CTC) criteria v4.03



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. > 60 years of age.
  2. Newly diagnosed AML according to the World Health Organization (WHO) 2016 either de novo AML or therapy-related AML (i.e AML arising after previous cytotoxic therapy or radiation)
  3. AML with favorable or intermediate cytogenetic risk according to Medical Research Council (MRC 2010) classification.
  4. Subjects should be eligible for intensive chemotherapy by Idarubicin, cytarabine, Lomustine.
  5. Eastern Cooperative Oncology Group (ECOG) performance status < 3 (appendix 1).
  6. SORROR score ≤ 3 (appendix 2).
  7. Adequate baseline organ function defined by the criteria below:

    • Total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) unless bilirubin rise is due to Gilbert's syndrome
    • Alanine Aminotransferase (ALAT) and Aspartate Transaminase (ASAT) ≤ 3xULN
    • creatinin clearance (Cockcroft-Gault) ≥ 30 ml/min
    • Unless considered due to leukemic organ involvement
  8. Adequate cardiac function with Left Ventricular Ejection Fraction (LVEF) ≥50%
  9. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
  10. Women will be menopausal to be enrolled
  11. The patient must give written (personally signed and dated) informed consent before completing any study-related procedure which means assessment or evaluation that would not form part of the normal medical care of the patient and before the start of induction chemotherapy.
  12. Affiliated to the French Social Security (Health Insurance).

Exclusion Criteria:

  1. Acute promyelocytic leukemia (APL) or acute megakaryocytic leukemia (AML-FAB M7).
  2. AML with adverse cytogenetic risk according to the MRC 2010 classification.
  3. AML arising from myelodysplastic syndromes, myeloproliferative disorders or chronic myelo-monocytic leukemia according to WHO classification (2016).
  4. AML with Philadelphia chromosome or with BCR-ABL1.
  5. Known active central nervous system leukemia
  6. Previous anti-AML treatment other than hydroxyurea.
  7. Cumulative anthracycline dose equivalent to ≥550 mg/m².
  8. Treatment with an investigational drug within 30 days or 5 half-life whichever is longer, preceding the first dose of study medication.
  9. Prior history of cancer unless controlled for at least 2 years and except for basal cell carcinoma, non-melanoma skin cancer and in situ cervical carcinoma.
  10. Severe medical or mental condition precluding the administration of protocol treatments
  11. Any sign of active uncontrolled disease including but not restricted to cardiac disease, infections, hepatitis.
  12. Any severe chronic disease potentially interfering with the protocol including HIV infection, active hepatitis B or C.
  13. Any severe conditions inducing contra-indications to dexamethasone including uncontrolled diabetes, infections, hypertension, stomach ulcer, mental illness, myasthenia or glaucoma.
  14. Any serious medical condition, laboratory abnormality, or psychiatric illness that would place the participant at an unacceptable risk or prevent them from giving informed consent.
  15. Known active HIV, Hepatitis B or C infection.
  16. Pregnancy or breastfeeding.
  17. Patients who are incapacitated, under wardship, legal guardianship, or under the protection of the courts.
  18. Patients under State Medical Assistance (AME).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03609060


Contacts
Layout table for location contacts
Contact: Christian RECHER, MD PD +33 5 31 15 63 55 recher.christian@iuct-oncopole.fr
Contact: Laetitia AUVRAY, Mrs +337 85 22 63 27 l.auvray.goelams@gmail.com

Locations
Layout table for location information
France
CHU ANGERS - Maladies du sang Recruiting
Angers, France, 49933
Contact: Mathilde HUNAULT, Dr    02 41 35 45 82    mahunault@chu-angers.fr   
Ch Avignon Not yet recruiting
Avignon, France, 84000
Contact: Safia CHEBREK, Dr    +33 4 32 75 93 00    chebrek.safia@ch-avignon.fr   
CH de la Côte Basque - Hématologie Not yet recruiting
Bayonne, France, 64109
Contact: Anne BANOS, Dr    +33 5 59 44 38 32    abanos@ch-cotebasque.fr   
CHRU JEAN MINJOZ - Hématologie Not yet recruiting
Besançon, France, 25030
Contact: Yohan DESBROSSES, Dr    +33 3 81 66 82 32    ydesbrosses@chu-besancon.fr   
CHU Brest - Hôpital Morvan - Hématologie Clinique Not yet recruiting
Brest, France, 29609
Contact: Gaëlle GUILLERM, Dr    +33 2 98 22 35 04    gaelle.guillerm@chu-brest.fr   
CH de Béziers - Hématologie Not yet recruiting
Béziers, France, 34500
Contact: Alain SAAD, Dr    +33 4 67 35 70 63    alain.saad@ch-beziers.fr   
Clinique du Parc - Hématologie Not yet recruiting
Castelnau-le-Lez, France, 34170
Contact: Carole EXBRAYAT, Dr    +33 4 67 33 15 12    carole.exbrayat@groupeclinipole.fr   
CHU Estaing - Hématologie Clinique Adulte Not yet recruiting
Clermont-Ferrand, France, 63000
Contact: Romain GUIEZE, Dr    +33 4 73 75 00 65    rguieze@chu-clermontferrand.fr   
CHU Grenoble - Hématologie Clinique Not yet recruiting
Grenoble, France, 38043
Contact: Martin CARRE, Dr    +33 4 76 76 57 55    mcarre1@chu-grenoble.fr   
Institut Paoli-Calmettes - Hématologie 2 Not yet recruiting
Marseille, France, 13000
Contact: Norbert VEY, Pr    +33 4 91 22 36 95    veyn@ipc.unicancer.fr   
CHR de Mercy - Hématologie Not yet recruiting
Metz, France, 57085
Contact: Véronique DORVAUX, Dr    +33 3 87 55 33 04    v.dorvaux@chr-metz-thionville.fr   
Hôpital Saint-Eloi - Hématologie Clinique Not yet recruiting
Montpellier, France, 34295
Contact: Yosr HICHERI, Dr    +33 4 67 33 24 18    y-hicheri@chu-montpellier.fr   
HOPITAL E. MULLER - Hématologie Not yet recruiting
Mulhouse, France, 68070
Contact: Mario OJEDA-URIBE, Dr    +33(0)3 89 64 77 55    ojeda-uribem@ghrmsa.fr   
CHU HOTEL DIEU - Hématologie Clinique Not yet recruiting
Nantes, France, 44093
Contact: Pierre PETERLIN², Dr    +33(0)2 40 08 32 71    pierre.peterlin@chu-nantes.fr   
CHR ORLEANS - Hématologie Recruiting
Orléans, France, 44100
Contact: Omar BENBRAHIM, Dr    +33(0)2 38 22 99 27    omar.benbrahim@chr-orleans.fr   
HOPITAL COCHIN - Hématologie Not yet recruiting
Paris, France, 75014
Contact: Lise WILLEMS, Dr    +33(0)1 58 41 26 70    lise.willems@aphp.fr   
CENTRE HOSPITALIER SAINTJEAN - Hématologie Clinique Not yet recruiting
Perpignan, France, 66000
Contact: Laurence SANHES, Dr    +33(0)4 68 61 89 02    laurence.sanhes@ch-perpignan.fr   
Hôpital Haut Levêque- CFM -Hématologie Clinique Et Thérapie Cellulaire Not yet recruiting
Pessac, France, 33604
Contact: Arnaud PIGNEUX, Pr    +33 5 57 65 65 11    arnaud.pigneux@chu-bordeaux.fr   
CHU La Milétrie - Hématologie Clinique Not yet recruiting
Poitiers, France, 86000
Contact: Maria-Pilar GALLEGO-HERNANZ, Dr    +33(0)5 49 44 44 44    maria-pilar.gallego-hernanz@chu-poitiers.fr   
CHU Reims - Hôpital Robert Debré - Hématologie Clinique Not yet recruiting
Reims, France, 51100
Contact: Chantal HIMBERLIN, Dr    +33(0)3 26 78 36 44    chimberlin@chu-reims.fr   
CHU Pontchaillou - Hématologie Not yet recruiting
Rennes, France, 35033
Contact: Marc BERNARD, Dr    +33(0)2 99 28 99 86    marc.bernard@chu-rennes.fr   
CHU Hautepierre - Hématologie Not yet recruiting
Strasbourg, France, 67098
Contact: Bruno LIOURE, Dr    +33(0)3 88 12 76 76    bruno.lioure@chru-strasbourg.fr   
Institut Universitaire du Cancer de Toulouse Oncopole - Service d'Hématologie Recruiting
Toulouse, France, 31059
Contact: Christian RECHER, Pr    +33 5 31 15 63 55    recher.christian@iuct-oncopole.fr   
CHU Bretonneau - Centre Henri Kaplan - Hématologie et Thérapie Cellulaire Not yet recruiting
Tours, France, 37044
Contact: Emmanuel GYAN, Pr    +33(0)2 47 47 37 12    emmanuel.gyan@univ-tours.fr   
CHU Nancy - Hopitaux Brabois Not yet recruiting
Vandœuvre-lès-Nancy, France, 54500
Contact: Gabrielle ROTH-GUEPIN, Dr    +33(0)3 83 15 76 86    g.roth-guepin@chru-nancy.fr   
Sponsors and Collaborators
French Innovative Leukemia Organisation
Investigators
Layout table for investigator information
Principal Investigator: Christian RECHER, MD PD +33 5 31 15 63 55

Additional Information:
Layout table for additonal information
Responsible Party: French Innovative Leukemia Organisation
ClinicalTrials.gov Identifier: NCT03609060     History of Changes
Other Study ID Numbers: DEXAML-02 (LAM-SA 2018)
First Posted: August 1, 2018    Key Record Dates
Last Update Posted: October 24, 2018
Last Verified: July 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by French Innovative Leukemia Organisation:
Elderly patients
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Dexamethasone
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action