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

Phase 1

Recruiting

• Conditions: untreated FLT3-mutated Acute Myeloid Leukemia; MedDRA version: 21.0Level: LLTClassification code: 10000886Term: Acute myeloid leukemia Class: 10029104; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-509834-20-00
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-29
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

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.

Exclusion Criteria

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), 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 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 o

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified