Clinical trial NCT00866281: A Study of the Safety and Preliminary Efficacy of Oral Midostaurin (PKC412) in Relapsed or Refractory Pediatric Leukemia
Official title: A Phase I/II, Open-label, Dose-escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Twice Daily Oral Midostaurin and to Evaluate the Preliminary Clinical and Pharmacodynamic Response in Pediatric Patients With Relapsed or Refractory Leukemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Keywords: Acute Myeloid Leukemia
AML
Acute Lymphoblastic Leukemia
ALL
midostaurin
PKC412
Pediatric relapsed or refractory FLT3 positive Acute Myeloid Leukemia
Pediatric relapsed or refractory Mixed-lineage leukemia gene rearranged Acute Lymphoblastic leukemia
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2009-03-20
Enrollment: 22
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase I/II pediatric dose-ranging study that will evaluate the safety, tolerability, clinical response, pharmacokinetics and pharmacodynamics of midostaurin in patients \<18 years of age who have relapsed or refractory acute leukemias that may benefit from administration of midostaurin, including MLL-rearranged ALL and FLT3 positive AML.


Eligibility criteria: Inclusion Criteria:

* Mixed-lineage leukemia (MLL) gene rearranged Acute Lymphoblastic Leukemia (ALL), that does not respond to treatment or has relapsed from prior treatment; or FLT3 mutated Acute Myeloid Leukemia (AML) that does not respond to a second treatment or has relapsed from 2 prior treatments
* Normal organ function, and chest x-ray
* Expected survival greater than 8 weeks
* Can care for most of personal needs and perform at least minimum activity

Exclusion Criteria:

* Patients with symptomatic leukemic central nervous system involvement or isolated extramedullary leukemia
* Patients must not have received other treatments for leukemia within a predefined time period, 72 hours for medications, 2 months for transplants
* Patients with heart function that is not normal
* Patients with HIV or hepatitis
* Patients with another severe disease or medical condition besides leukemia Other protocol-defined inclusion/exclusion criteria may apply

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Midostaurin- Posterior Probability of DLT
timeFrame: Baseline, End of dose escalation phase (6 months)
Secondary outcomes:
measure: Percentage of Participants With Best Overall Response by Indication
timeFrame: Baseline, Day 15 (Day 1 of Cycle 2), Day 22 (Day 8 of Cycle 2), Day 29(Day 1 of Cycle 9), End of treatment (up to 24 months after last dose or until death whichever occurred first)
measure: Time to Response With Midostaurin
timeFrame: Baseline, End of treatment (up to 24 months after last dose or until death whichever occurred first)
measure: Overall Survival With Midostaurin
timeFrame: Baseline, End of treatment (up to 24 months after last dose or until death whichever occurred first)
measure: Plasma Concentrations of Midostaurin and Its Metabolites CGP52421 and CGP62221
timeFrame: Day 1, Day 5, Day 7, Day 15 (Day 1 of Cycle 2), Day 29 (Day 1 of Cycle 3)
measure: Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Treatment Related AEs or SAEs and Death During the Study
timeFrame: Baseline (start of study treatment) up to End of treatment (up to 24 months after last dose or until death whichever occurred first)
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Seattle Children's Hospital CPKC412A2114
state: Washington
city: Paris Cedex 19
country: France
facility: Novartis Investigative Site
city: Genova
country: Italy
facility: Novartis Investigative Site
state: GE
city: Monza
country: Italy
facility: Novartis Investigative Site
state: MB
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Torino
country: Italy
facility: Novartis Investigative Site
state: TO
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: