Authorised Therapeutic exploratory (Phase II) untreated FLT3-mutated Acute Myeloid Leukemia

A global study of midostaurin in combination with chemotherapy to evaluate safety, efficacy, and pharmacokinetics in newly diagnosed pediatric patients with FLT3-mutated AML

EU CTIS ID: 2023-509834-20-00

What this study is testing

Part 2: To evaluate safety and tolerability of midostaurin (30mg/m2 bid or 1 mg/kg bid for participants <10 kg body weight) in sequential combination with chemotherapy followed by 12 cycles of midostaurin post-consolidation therapy in pediatric participants with newly diagnosed FLT3-mutated AML.

  • Therapeutic exploratory (Phase II)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

  • Documented diagnosis of previously untreated de novo AML according to WHO 2016 criteria except acute promyelocytic leukemia. Participants may have received up to 7 days of hydroxyurea or low-dose cytarabine therapy prior to the first chemotherapy dose administered in Block 1, if clinically indicated at the discretion of the investigator. Administration of intrathecal chemotherapy is permitted before receiving study treatment when administered as part of an initial diagnostic lumbar puncture or thereafter according to local Standard of Care (SOC). Participants may begin the first local induction chemotherapy as part of Block 1 while the results of their FLT3 analysis are pending.
  • Presence of a FLT3 mutation, as measured/confirmed by a Novartis designated central laboratory or a local laboratory that has successfully passed the Novartis laboratory qualification procedure with results available prior to first dose of midostaurin: ● juxtamembrane internal tandem duplication (ITD), as determined by PCR based on a mutant/wild type signal ratio cutoff of ≥ 0.05 ● and/or mutation in the tyrosine kinase domain (TKD) as determined by PCR (mutant/wild type signal ratio cutoff of ≥ 0.05) or NGS
  • Participants from 3 months of age to less than 18 years of age with expected survival of greater than 12 weeks.
  • Participants with Lansky or Karnofsky performance status ≥ 60. The Lansky performance status will be used for participants from 1 year to 16 years old, and the Karnofsky performance status will be used for participants ≥16 years old.
  • Participants with the following laboratory values that indicate adequate organ function: ● Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times upper limit of normal (ULN) ● Serum total bilirubin ≤ 1.5 times ULN, unless in case of hyperbilirubinemia due to an isolated Gilbert’s syndrome ● Estimated creatinine clearance ≥ 30 mL/min based on “bedside formula” by Schwartz and Work 2009. ● These values should be collected at baseline/before the start of the local chemotherapy and also prior to midostaurin intake
  • The parent or legal guardian and/or the participant will have provided written informed consent according to local laws and regulations prior to any study related screening procedures being performed.

You likely can't join if

  • Patients with any of the following oncologic diagnoses are not eligible: a) Any concurrent malignancy, juvenile myelomonocytic leukemia (JMML), Philadelphia chromosome or bcr-abl1 positive AML, biphenotypic or bilineal acute leukemia, acute myeloid leukemia associated to down syndrome (AML-DS), acute myeloid leukemia arising from myelodysplasia or other preceding hematologic malignancy, or therapy-related myeloid neoplasms. b) Patients with symptomatic leukemic CNS involvement. c) Patients with isolated extramedullary leukemia, secondary AML and MDS. d) Patients with Acute Promyelocytic Leukemia (APL).
  • Known impairment of gastrointestinal (GI) function or GI disease that might alter significantly the absorption of midostaurin.
  • Known confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis.
  • Left ventricular shortening fraction of < 27%, as determined by MUGA scan or echocardiogram.
  • Patients who are under 2.5 kg of body weight.
  • Abnormal electrocardiogram (ECG) finding, including: ● QTcF ≥ 450 msec (for female children over 12 years: QTcF ≥ 460 msec), PR ≥ 200 msec, or QRS complex ≥ 110 msec at screening or prior to the first dose of study drug. ● Any clinically relevant cardiac conduction abnormality. ● Any clinically relevant morphologic abnormality. ● Any clinically relevant ST/T wave abnormality. ● Any clinically relevant atrial or ventricular arrhythmia.
See the full eligibility criteria
Who can join
  • Documented diagnosis of previously untreated de novo AML according to WHO 2016 criteria except acute promyelocytic leukemia. Participants may have received up to 7 days of hydroxyurea or low-dose cytarabine therapy prior to the first chemotherapy dose administered in Block 1, if clinically indicated at the discretion of the investigator. Administration of intrathecal chemotherapy is permitted before receiving study treatment when administered as part of an initial diagnostic lumbar puncture or thereafter according to local Standard of Care (SOC). Participants may begin the first local induction chemotherapy as part of Block 1 while the results of their FLT3 analysis are pending.
  • Presence of a FLT3 mutation, as measured/confirmed by a Novartis designated central laboratory or a local laboratory that has successfully passed the Novartis laboratory qualification procedure with results available prior to first dose of midostaurin: ● juxtamembrane internal tandem duplication (ITD), as determined by PCR based on a mutant/wild type signal ratio cutoff of ≥ 0.05 ● and/or mutation in the tyrosine kinase domain (TKD) as determined by PCR (mutant/wild type signal ratio cutoff of ≥ 0.05) or NGS
  • Participants from 3 months of age to less than 18 years of age with expected survival of greater than 12 weeks.
  • Participants with Lansky or Karnofsky performance status ≥ 60. The Lansky performance status will be used for participants from 1 year to 16 years old, and the Karnofsky performance status will be used for participants ≥16 years old.
  • Participants with the following laboratory values that indicate adequate organ function: ● Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times upper limit of normal (ULN) ● Serum total bilirubin ≤ 1.5 times ULN, unless in case of hyperbilirubinemia due to an isolated Gilbert’s syndrome ● Estimated creatinine clearance ≥ 30 mL/min based on “bedside formula” by Schwartz and Work 2009. ● These values should be collected at baseline/before the start of the local chemotherapy and also prior to midostaurin intake
  • The parent or legal guardian and/or the participant will have provided written informed consent according to local laws and regulations prior to any study related screening procedures being performed.
What rules you out
  • Patients with any of the following oncologic diagnoses are not eligible: a) Any concurrent malignancy, juvenile myelomonocytic leukemia (JMML), Philadelphia chromosome or bcr-abl1 positive AML, biphenotypic or bilineal acute leukemia, acute myeloid leukemia associated to down syndrome (AML-DS), acute myeloid leukemia arising from myelodysplasia or other preceding hematologic malignancy, or therapy-related myeloid neoplasms. b) Patients with symptomatic leukemic CNS involvement. c) Patients with isolated extramedullary leukemia, secondary AML and MDS. d) Patients with Acute Promyelocytic Leukemia (APL).
  • Known impairment of gastrointestinal (GI) function or GI disease that might alter significantly the absorption of midostaurin.
  • Known confirmed diagnosis of human immunodeficiency virus (HIV) infection or active viral hepatitis.
  • Left ventricular shortening fraction of < 27%, as determined by MUGA scan or echocardiogram.
  • Patients who are under 2.5 kg of body weight.
  • Abnormal electrocardiogram (ECG) finding, including: ● QTcF ≥ 450 msec (for female children over 12 years: QTcF ≥ 460 msec), PR ≥ 200 msec, or QRS complex ≥ 110 msec at screening or prior to the first dose of study drug. ● Any clinically relevant cardiac conduction abnormality. ● Any clinically relevant morphologic abnormality. ● Any clinically relevant ST/T wave abnormality. ● Any clinically relevant atrial or ventricular arrhythmia.
  • Pregnant or nursing (lactating) females
  • Female patients of child-bearing potential (e.g., are menstruating), who do not agree to abstinence or, if sexually active, do not agree to the use of effective contraception during dosing and for at least 4 months after stopping midostaurin (or as per their respective local labels of the chemotherapeutic drugs, whichever is longer) (as defined in Section 7.2.2.7.6). Highly effective contraception methods include: ● Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). 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), or total hysterectomy, 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 participant. ● Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception
  • If they don’t agree to abstinence, sexually active males must use condom during intercourse while taking the drug and for at least 4 months after stopping midostaurin (or as per their respective local labels of the chemotherapeutic drugs, whichever is longer) and should not father a child in this period.
  • Patients/parents unwilling or unable to comply with the protocol.
  • Hypersensitivity to midostaurin, cytarabine, daunorubicin/idarubicin, fludarabine, etoposide or mitoxantrone or to any of the excipients
  • Any prior chemotherapy (excluding Block 1 local induction chemotherapy), radiation or any other treatment for leukemia, or any prior allogeneic, syngeneic or autologous bone marrow or stem cell transplant; however patients may have received up to 7 days of hydroxyurea or low- dose cytarabine therapy prior to the first dose of chemotherapy administration in Block 1, if clinically indicated at the discretion of the investigator. Administration of intrathecal chemotherapy is permitted before receiving study treatment when administered as part of an initial diagnostic lumbar puncture or thereafter according to local Standard of Care (SOC)
  • Patients who have received any investigational agent (excluding Block 1 local induction chemotherapy) within 30 days or 5 half-lives, whichever is greater, prior to the start of study treatment.
  • Patients who have received prior treatment with a FLT3 inhibitor (including sorafenib, lestaurtinib, or quizartinib). However, up to 1 week of FLT3 inhibitor (except midostaurin) exposure prior to study enrollment is permissible.
  • Patients who take strong CYP3A4/5 enzyme inducing drugs or strong CYP3A4/5 enzyme inducing herbal supplements (see Appendix 2) unless they can be discontinued or replaced prior to enrollment.
  • Patients who have had any surgical procedure, excluding central venous catheter placement or other minor procedures (e.g., skin or bone marrow biopsy), within 14 days of start of study treatment.
  • Patients with any other known disease or concurrent severe and/or uncontrolled medical condition (e.g., cardiovascular disease including congestive heart failure or active uncontrolled infection) that could compromise participation in the study.
  • Presence of clinically active uncontrolled infection including significant bacterial, fungal, viral or parasitic infection requiring treatment. Infections are considered controlled if appropriate therapy has been instituted and, at the time of screening, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs; worsening radiography finding in the optional chest X-ray attributable to infection or other clinically significant pulmonary conditions. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
  • Patients with Fanconi anemia, Schwachman syndrome, any other known bone marrow failure syndrome, or constitutional trisomy 21 or with constitutional mosaicism of trisomy 21.

The study team makes the final eligibility decision.

Where it's taking place

  • Turkey
  • Jordan
  • Russian Federation
  • Korea, Republic of

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 0-17 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Turkey; Jordan; Russian Federation; Korea, Republic of. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.