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Study to Improve OS in 18 to 60 Year-old Patients, Comparing Daunorubicin Versus High Dose Idarubicin Induction Regimens, High Dose Versus Intermediate Dose Cytarabine Consolidation Regimens, and Standard Versus MMF Prophylaxis of GvHD in Allografted Patients in First CR

NCT02416388

Description:

This open label, multicenter phase II/III study with multiple randomization phases at differents stages of AML treatment (induction, consolidation and HSCT where applicable) is designed to improve OS in younger (18 to 60 year-old) patients, with AML risk-adapted patient strategies. Within the intermediate risk AML group, optimal GvHD prophylaxis following allogeneic SCT in first CR, after either myeloablative (MAC) or reduced intensity (RIC) conditioning, will also be evaluated. With an adaptative design, this clinical trial could test up to 3 novel AML agents of interest.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study to Improve OS in 18 to 60 Year-old Patients, Comparing Daunorubicin Versus High Dose Idarubicin Induction Regimens, High Dose Versus Intermediate Dose Cytarabine Consolidation Regimens, and Standard Versus MMF Prophylaxis of GvHD in Allografted Patients in First CR
  • Official Title: Phase II/III Randomized Study to Improve Overall Survival in 18 to 60 Year-old Patients, Comparing Daunorubicin Versus High Dose Idarubicin Induction Regimens, High Dose Versus Intermediate Dose Cytarabine Consolidation Regimens, and Standard Versus Mycophenolate Mofetil Prophylaxis of Graft Versus Host Disease in Allografted Patients in First CR : a Backbone InterGroup-1 Trial

Clinical Trial IDs

  • ORG STUDY ID: PHRC-2010-03
  • NCT ID: NCT02416388

Conditions

  • Acute Myeloid Leukemia (AML)

Interventions

DrugSynonymsArms
IdarubicinR1-IDA
DaunorubicinR1-DAUNO
HD CytarabineR2-HDAC
CyclosporineR3-MAC-MPA
MethotrexateR3-MAC-MTX
Mycophenolic acid (MPA)R3-MAC-MTX
vosaroxinR4-VOS-IDAC
ID cytarabineR2-IDAC

Purpose

This open label, multicenter phase II/III study with multiple randomization phases at differents stages of AML treatment (induction, consolidation and HSCT where applicable) is designed to improve OS in younger (18 to 60 year-old) patients, with AML risk-adapted patient strategies. Within the intermediate risk AML group, optimal GvHD prophylaxis following allogeneic SCT in first CR, after either myeloablative (MAC) or reduced intensity (RIC) conditioning, will also be evaluated. With an adaptative design, this clinical trial could test up to 3 novel AML agents of interest.

Trial Arms

NameTypeDescriptionInterventions
R1-IDAExperimentalIdarubicin
  • Idarubicin
R1-DAUNOActive ComparatorDaunorubicin
  • Daunorubicin
R2-HDACActive ComparatorHigh dose cytarabine
  • HD Cytarabine
R2-IDACExperimentalIntermediate dose cytarabine
  • ID cytarabine
R3-MAC-MTXActive ComparatorMethotrexate and mycophenolic acid
  • Methotrexate
  • Mycophenolic acid (MPA)
R3-MAC-MPAExperimentalCyclosporine and mycophenolic acid
  • Cyclosporine
  • Mycophenolic acid (MPA)
R3-RIC-CICLOActive ComparatorCyclosporine
  • Cyclosporine
R3-RIC-MPAExperimentalCyclosporine and mycophenolic acid
  • Cyclosporine
  • Mycophenolic acid (MPA)
R4-VOS-IDACExperimentalIntermediate dose cytarabine and vosaroxin
  • vosaroxin
  • ID cytarabine
R4-IDACActive ComparatorIntermediate dose cytarabine
  • ID cytarabine

Eligibility Criteria

        Inclusion Criteria (at diagnosis) :

          1. Age ≥ 18 years and < 61 years

          2. With a newly diagnosed de novo or secondary type AML (post myelodysplastic syndrome
             MDS or therapy-related AML)

          3. No prior treatment for AML, with the exception of hydroxyurea

          4. ECOG performance status ≤ 3

          5. No contraindication to anthracyclines : decompensated or uncontrolled heart failure,
             recent myocardial infarction, current signs of cardiac impairment, uncontrolled
             arrhythmias, LVEF (left ventricular ejection fraction) < 50%

          6. Total bilirubin ≤ 2 x upper limit of normal (UNL), ASAT(SGOT) and ALAT (SGPT) ≤ 2.5 X
             UNL, creatinine < 150 µmol/l, unless AML-related out of range values

          7. Women of childbearing potential should use appropriate methods of contraception

          8. Health insurance coverage

          9. Signed informed consent

        Exclusion criteria (at diagnosis) :

          1. Patients with acute promyelocytic leukemia (APL), as confirmed either by t(15;17) or
             by the presence of PML-RARA fusion transcripts

          2. Patients with core binding factor (CBF) AML, as confirmed either by t(8;21), t(16,16)
             or inv(16), or by fusion transcripts resulting from these cytogenetic abnormalities
             (RUNX1-RUNX1T1, CBFB-MYH11).

          3. Patients with secondary AML arising from myeloproliferative disorders previously known
             according to the 2008 WHO classification

          4. Patients with Ph1+ AML or previous Ph1+ disorder (chronic myelogenous leukemia)

          5. Severe pshyciatric or organic disorder, supposed to be independent from AML, that
             would contraindicate treatment, including allogeneic HSCT

          6. No psychological, familial, social, or geographic reason that would compromise
             clinical follow up

          7. History of uncontrolled cancer for the last 2 years, with the exception of basal cell
             carcinoma or carcinoma in situ of the cervix

          8. Uncontrolled severe infection

          9. Patients with positive serology for HIV-1 and -2, or HTLV -1 and -2, or active
             hepatitis virus B or C infection

         10. Pregnant or lactating women

         11. Legal incapacity (patients under tutorship, curatorship or judicial protection)

        For randomization R4-VOS (post-induction/salvage):

        Inclusion criteria

          1. Patients enrolled in the BIG-1 trial at diagnosis

          2. Patients achieving first CR/CRp/CRi after induction or salvage therapy (within 15 days
             before R4-VOS)

          3. Favorable or intermediate risk AML patients, as stratified with BIG-1 prognostic
             classification

          4. Patients randomized to R2-IDAC arm (intermediate dose cytarabine)

          5. ECOG performance status ≤ 2

          6. Left ventricular ejection fraction (LVEF) at least 40% by multiple gated acquisition
             (MUGA) scan or echocardiogram (ECHO)

          7. Local clinical laboratory values as follows:

               -  Serum creatinine ≤ 2.0 mg/dL

               -  Total bilirubin ≤ 1.5 X the upper limit of normal (ULN)

               -  Aspartate aminotransferase (AST) ≤ 2.5 X ULN

               -  Alanine aminotransferase (ALT) ≤ 2.5 X ULN

          8. Signed written informed consent for vosaroxin study (R4-VOS)

          9. Women of childbearing potential must have a negative pregnancy test within 8 days
             before randomization R4-VOS and commit to the use of effective contraception during
             the period of treatment and up to 36 days after vosaroxin has been stopped. Men must
             use effective contraception during the treatment period and up to 96 days after
             vosaroxin has been stopped.

        Exclusion criteria

          1. Severe uncontrolled infection such as sepsis, or multiple organ dysfunction syndrome,
             uncontrolled fever

          2. Documented uncontrolled fungal infection (positive blood test and cultures)

          3. History of myocardial infarction, unstable angina, cerebrovascular accident (CVA) or
             transient ischemic attack (TIA) in the 3 months before randomization

          4. Patient under hemodialysis (HD) or peritoneal dialysis (PD)

        For randomization R3 (before AlloHSCT):

        Inclusion criteria

          1. Patients enrolled in the BIG-1 trial at diagnosis

          2. Patients achieving first CR after induction or salvage therapy

          3. Patients belonging to the intermediate AML risk group as defined in the protocol BIG-1

          4. Signed informed consent for R3
      
Maximum Eligible Age:61 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival
Time Frame:3 years
Safety Issue:
Description:For randomizations R1 (idarubicine vs daunorubicine) and R2 (HDAC vs IDAC)

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University Hospital, Angers

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