Clinical Trials /

Standard of Care +/- Midostaurin to Prevent Relapse Post Stem Cell Transplant in Patients With FLT3-ITD Mutated AML

NCT01883362

Description:

To determine if the addition of midostaurin (PKC412) to Standard of Care (SOC) therapy reduces relapse in FLT3-ITD mutated AML patients receiving an allogenetic hematopoietic stem cell transplant,

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Standard of Care +/- Midostaurin to Prevent Relapse Post Stem Cell Transplant in Patients With FLT3-ITD Mutated AML
  • Official Title: A Phase II, Randomized Trial of Standard of Care, With or Without Midostaruin to Prevent Relapse Following Allogeneic Hematopoietic Stem Cell Transplantation in Patients With FLT3-ITD Mutated Acute Myeloid Leukemia

Clinical Trial IDs

  • ORG STUDY ID: CPKC412AUS23
  • NCT ID: NCT01883362

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Midostaurin (PKC412)PKC412, MidostaurinStandard of Care (SOC) with Midostaurin

Purpose

To determine if the addition of midostaurin (PKC412) to Standard of Care (SOC) therapy reduces relapse in FLT3-ITD mutated AML patients receiving an allogenetic hematopoietic stem cell transplant,

Trial Arms

NameTypeDescriptionInterventions
Standard of Care (SOC) with MidostaurinExperimentalPatients will receive standard of care in the post SCT setting in addition to Midostaurin 50mg twice a day for 12 months (cycles).
  • Midostaurin (PKC412)
Standard of Care (SOC)Active ComparatorPatients will receive standard of care alone in the post SCT setting

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Patients must be between 18 and 60 years of age
    
              -  Patients must have an ECOG Performance Status of < 2
    
              -  Patients must have a documented Unequivocal diagnosis of AML according to WHO 2008
                 classification (>20% blasts in the bone marrow), excluding M3 (acute promyelocytic
                 leukemia).
    
              -  Patients must have a documented FLT3 ITD mutation, determined by local laboratory for
                 eligibility (historical tissue will be requested for central analysis confirmation)
    
              -  Patients who have undergone allogeneic HSCT in CR1 from a matched related or matched
                 unrelated donor. All of the following criteria must also be met:
    
            HLA typing to include available 8/8 or 7/8 allele HLA matched donor (at A,B,C, DRB1) Single
            allelic mismatch allowed • Patients who received a conditioning regimen which included one
            of the following: Busulfan/Fludarabine (Bu/Flu) Busulfan (16 mg/kg PO or 12.8 mg/kg IV)
            Fludarabine (120-180 mg/m2) Fludarabine / Melphalan (Flu/Mel) Fludarabine (120-180 mg/m2)
            Melphalan (≤ 150 mg/m2) Busulfan/Cyclophosphamide (Bu/Cy) Busulfan (16 mg/kg PO or 12.8
            mg/kg IV) Cyclophosphamide (120 mg/kg) Cyclophosphamide/Total Body Irradiation (Cy/TBI)
            Cyclophosphamide (120 mg/kg) TBI (1200-1420 cGy)
    
            • Recovery of counts by day 42 and able to start midostaurin by day 60 post-HSCT (first
            dose of midostaurin to start no earlier than 28 days post-HSCT); ANC >1000µL, platelets
            ≥20,000 without platelet transfusion
    
            Exclusion Criteria:
    
              -  Patients whom have failed prior attempts at allogeneic HSCT
    
              -  Patients who have received an autologous transplant
    
              -  Patients with Acute GVHD Grade III-IV
    
              -  Patients with a known confirmed diagnosis of HIV infection or active viral hepatitis.
    
              -  Impaired cardiac function including any of the following:
    
                   -  Screening ECG with a QTc > 450 msec. If QTc > 450 and electrolytes are not within
                      normal ranges, electrolytes should be corrected and then the patient rescreened
                      for QTc.
    
                   -  Patients with congenital long QT syndrome
    
                   -  History or presence of sustained ventricular tachycardia
    
                   -  Any history of ventricular fibrillation or torsades de pointes
    
                   -  Bradycardia defined as HR. < 50 bpm
    
                   -  Right bundle branch block + left anterior hemiblock (bifascicular block)
    
                   -  Patients with myocardial infarction or unstable angina < 6 months prior to
                      starting study
    
                   -  Congestive Heart Failure NY Heart Association class III or IV
    
                   -  Patients with an ejection fraction < 45% assessed by MUGA or ---ECHO within 28
                      days prior to starting study cycle 1 (of midostaurin or control group)
    
              -  Patients with any pulmonary infiltrate including those suspected to be of infectious
                 origin (unless resolves to ≤ Grade 1 within screening timeframe)
    
              -  Patient requires treatment with strong CYP3A4 inhibitors or moderate or strong CYP3A4
                 inducers other than those required for GVH or infection prophylaxis or treatment
    
            Pregnant or nursing (lactating) women, or women of child-bearing potential, must use highly
            effective methods of contraception during dosing and for 30 days after treatment completion
    
            Other protocol-defined inclusion/exclusion criteria may apply
          
    Maximum Eligible Age:60 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Relapse Free Survival (RFS)
    Time Frame:18 months from date of transplant
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Disease Free Survival (DFS)
    Time Frame:for at least 24 months from date of transplant or study completion
    Safety Issue:
    Description:
    Measure:Non-Relapse Mortality (NRM)
    Time Frame:for at least 24 months from date of transplant or study completion
    Safety Issue:
    Description:
    Measure:Overall Survival (OS)
    Time Frame:for at least 24 months from date of transplant or study completion
    Safety Issue:
    Description:
    Measure:FLT3-ITD mutation status centrally in archived material from diagnosis (if available) including mutant:wild type ratio
    Time Frame:upto 24 months from date of transplannt or at study completion
    Safety Issue:
    Description:
    Measure:Number of Participants with Adverse Events as a Measure of Safety and Tolerability
    Time Frame:12 months
    Safety Issue:
    Description:The assessment of safety will be based mainly on the frequency of Adverse Events (AEs), on the number of laboratory values summarized by CTCAE grades and non-relapse mortality(NRM). The assessment of tolerability will be based on whether midostaurin can be administered at a daily dose of 50mg twice daily at least 80% of the time to 50% or more of patients during the first 100 days after allogeneic HSCT
    Measure:Plasma Pharmacokinetics (PK) of midostaurin and the metabolites: CGP62221 and CGP52421: Pre-dose levels
    Time Frame:Pre-dose on days 1 and 15 of Cycle 1, on day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
    Safety Issue:
    Description:Pre-dose levels (Cmin) will be directly determined from raw plasma concentration-time data (units ng/ml)
    Measure:Plasma Pharmacokinetics (PK) of midostaurin and the metabolites: CGP62221 and CGP52421: Pre-dose levels
    Time Frame:Pre-dose collection two weeks following initiation of strong CYP3A4 inhibitors
    Safety Issue:
    Description:Pre-dose levels (Cmin) will be directly determined from raw plasma concentration-time data (units ng/ml)

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Completed
    Lead Sponsor:Novartis Pharmaceuticals

    Trial Keywords

    • acute myeloid leukemia
    • AML
    • FLT3-ITD
    • midostaurin
    • PKC412
    • allogeneic hematopoeitic stem cell tranplant
    • SCT
    • HSCT
    • CR1

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