A Phase II, open-label, single arm study to evaluate the safety, efficacy, and pharmacokinetics of twice daily midostaurin (PKC412) combined with standard chemotherapy and as a single agent post-consolidation therapy in children with untreated FLT3-mutated AML -

OVARTIS PHARMA AG0 sites52 target enrollmentJanuary 29, 2021

DrugsDaunoxome

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Not specified
Sponsor: OVARTIS PHARMA AG
Enrollment: 52
Status: Active, not recruiting
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

No summary available.

Registry

who.int

Start Date

January 29, 2021

End Date

TBD

Last Updated

5 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Investigators

Sponsor

OVARTIS PHARMA AG

Eligibility Criteria

Inclusion Criteria

•1\. Documented diagnosis of previously untreated de novo AML according to WHO 2016 criteria except acute promyelocytic leukemia. Patients 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). Patients may begin the first local induction chemotherapy as part of Block 1 while the results of their FLT3 analysis are pending.
•2\. Presence of a FLT3 mutation, 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
•3\. Patients from 3 months of age to less than 18 years of age with expected survival of greater than 12 weeks.
•4\. Patients with Lansky or Karnofsky performance status \= 60\. The Lansky performance status will be used for patients from 1 year to 16 years old, and the Karnofsky performance status will be used for patients \=16 years old.
•5\. Patients 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 syndrome

Exclusion Criteria

•1\. 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).
•2\. 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).
•3\. 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.
•4\. Patients who have received prior treatment with a FLT3 inhibitor (including sorafenib, lestaurtinib, or quizartinib).
•5\. Patients who take strong CYP3A4/5 enzyme inducing drugs or strong CYP3A4/5 enzyme inducing herbal supplements (see protocol Appendix 2\) unless they can be discontinued or replaced prior to enrollment.
•6\. 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.