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Study to Assess the Safety and Efficacy of Midostaurin (PKC412) in Combination With Standard Chemotherapy During Induction and Consolidation Followed by 12 Months of Monotherapy in Patients With Newly-diagnosed FLT3-mutated Acute Myeloid Leukemia.

NCT03379727

Description:

The purpose of this study is to gather and evaluate additional safety and efficacy data on the combination of midostaurin and standard of care for adult patients with newly diagnosed Fms-like tyrosine kinase receptor (FLT3) mutated Acute Myeloid Leukemia (AML) who are eligible for standard induction and consolidation

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study to Assess the Safety and Efficacy of Midostaurin (PKC412) in Combination With Standard Chemotherapy During Induction and Consolidation Followed by 12 Months of Monotherapy in Patients With Newly-diagnosed FLT3-mutated Acute Myeloid Leukemia.
  • Official Title: An Open-label, Multi-Center, Phase IIIb Study to Assess the Safety and Efficacy of Midostaurin (PKC412) in Patients 18 Years of Age or Older With Newly-diagnosed FLT3-mutated Acute Myeloid Leukemia Who Are Eligible for "7+3" or "5+2" Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: CPKC412A2408
  • SECONDARY ID: 2016-004440-12
  • NCT ID: NCT03379727

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
MidostaurinMidostaurin

Purpose

The purpose of this study is to gather and evaluate additional safety and efficacy data on the combination of midostaurin and standard of care for adult patients with newly diagnosed Fms-like tyrosine kinase receptor (FLT3) mutated Acute Myeloid Leukemia (AML) who are eligible for standard induction and consolidation

Trial Arms

NameTypeDescriptionInterventions
MidostaurinExperimentalInduction phase - D8 to D28 in combination with standard of care (7+3 or 5+2 chemotherapy) up to 2 cycles Consolidation phase - D8 to D28 in combination with cytarabine up to 4 cycles Maintenance phase - D1 to D28 up to 12 cycles
  • Midostaurin

Eligibility Criteria

        Inclusion Criteria:

        Patients eligible for inclusion in this study have to meet all of the following criteria:

          1. Written informed consent must be obtained prior to any screening procedures.

          2. Patients must be 18 years of age or older at the time of signing informed consent.

          3. Patients must have a documented unequivocal diagnosis of AML according to WHO 2008
             classification. A bone marrow or blood blast count of ≥ 20% is required, except for
             AML with t(15;17), t(8;21), inv(16) or t(16;16) where blast count may be <20%, and,
             excluding M3 (acute promyelocytic leukemia).

          4. Patients with secondary AML are eligible, e.g. patients with antecedent history of
             treatment for prior malignancy. AML patients with a history of antecedent treatment
             for myelodysplasia (MDS), e.g. azacitidine or decitabine, remain eligible for
             treatment on this study. These agents must have been discontinued for a period of at
             least 30 days or 5 half-lives of the drug (whichever is greater) before midostaurin
             can be administered.

          5. Patients must have started "7+3" or "5+2" first induction chemotherapy regimen.

          6. Patients must have a documented FLT3 mutation (ITD or TKD).).

          7. Patients must have an ECOG Performance Status of ≤ 2

          8. Patients requiring intrathecal chemotherapy must have a minimum washout of 48 hours
             prior to the first dose of midostaurin

          9. Patients must have Total Bilirubin ≤ 2.5 x ULN

         10. Patients must have Serum Creatinine ≤ 2.5 x ULN

         11. Patients must be able to communicate well with the investigator to understand and
             comply with the requirements of the study

         12. Women of child-bearing potential must have a negative pregnancy test before starting
             use of midostaurin.

        Exclusion criteria:

        Patients eligible for this study must not meet any of the following criteria:

          1. Prior therapy for AML with the following exceptions:

               1. emergency leukapheresis

               2. emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 7 days

               3. cranial RT for CNS leukostasis (one dose only)

               4. growth factor/cytokine support

          2. Patients with LVEF less than 45% (by echocardiogram or MUGA) or symptomatic congestive
             heart failure (Class III or IV) according to New York Heart Association (NYHA)
             classification

          3. Patients with any pulmonary infiltrate including those suspected to be of infectious
             origin (unless resolved to ≤ Grade 1 within screening timeframe)

          4. Patients with any uncontrolled illness, including, but not limited to, acute or
             chronic pancreatitis or uncontrolled infection

          5. QTc >470 msec on screening ECG.

          6. History of hypersensitivity to any drugs or metabolites of similar chemical classes as
             the study treatment.

          7. Participation in a prior investigational interventional (drug) study with
             administration of the investigational product within 30 days or 5 half-lives of the
             investigational product, whichever is longer.

          8. Pregnancy statements and contraception requirements:

             Women of child-bearing potential, defined as all women physiologically capable of
             becoming pregnant, unless they are using highly effective methods of contraception
             during dosing and for at least 4 months after stopping medication. Highly effective
             contraception methods include:

               -  Total abstinence (when this is in line with the preferred and usual lifestyle of
                  the subject). Periodic abstinence (e.g. calendar, ovulation, symptothermal,
                  post-ovulation methods) and withdrawal are not acceptable methods of
                  contraception

               -  Female sterilization (have had surgical bilateral oophorectomy with or without
                  hysterectomy), total hysterectomy, or tubal ligation at least six weeks before
                  taking study treatment. In case of oophorectomy alone, only when the reproductive
                  status of the woman has been confirmed by follow up hormone level assessment

               -  Male sterilization (at least 6 months prior to screening). The vasectomized male
                  partner should be the sole partner for that subject

               -  Use of oral, injected or implanted hormonal methods of contraception or placement
                  of an intrauterine device or intrauterine system, or other forms of hormonal
                  contraception that have comparable efficacy (failure rate <1%), for example
                  hormone vaginal ring or transdermal hormone contraception.

             In case of use of oral contraception women should also add a barrier method of
             contraception, particularly as it is currently unknown whether midostaurin may reduce
             the effectiveness of hormonal contraceptives.

             Sexually-active males unless they use a condom during intercourse with females of
             reproductive potential or pregnant women and for at least 4 months after stopping
             treatment to avoid conception or embryo-fetal harm.

          9. Patients enrolled in this study are not permitted to participate in additional
             parallel study drug or device studies.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of patients with AEs, Grade 3&4 AEs, SAEs, AEs leading to discontinuation, and deaths up to 24 months.
Time Frame:Baseline up to approximatly 24 months
Safety Issue:
Description:To further assess the safety of midostaurin in induction, consolidation and maintenance therapy, including, the "7+3" regimen, higher dose of Daunorubicin (60-90mg/m2/day), the substitution of Daunorubicin by Idarubicin and lower dose of Cytarabine (100-200 mg/m2/day) and also allowing the "5+2" reduced dose regimen.

Secondary Outcome Measures

Measure:Percentage of patients with CR/CRi as per local assessment
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description:CR/CRi rate is defined as the percentage of patients with complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) as per local assessment, in induction, consolidation and maintenance phase. CR/CRi rate will be calculated based on the full analysis set (FAS).

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • Midostaurin
  • PKC412
  • FMS-like tyrosine kinase receptor
  • FLT3
  • Acute Myeloid Leukemia
  • AML
  • 7+3 chemotherapy
  • 5+2 chemotherapy
  • Daunorubicin
  • Idarubicin
  • Cytarabine

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