A Study of the Safety and Preliminary Efficacy of Oral Midostaurin (PKC412) in Relapsed or Refractory Pediatric Leukemia

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
First received: March 19, 2009
Last updated: November 7, 2014
Last verified: November 2014
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.

Condition Intervention Phase
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Drug: midostaurin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • to determine the maximum tolerated dose for two age groups (3 months to 2 years; and >2 years to <18 years) based on the rate of dose-limiting toxicity (DLT) within the equivalent dose ranges studied in adults [ Time Frame: primarily the first cycle of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • to characterize acute and chronic safety and tolerability [ Time Frame: Continuous ] [ Designated as safety issue: Yes ]
  • to characterize the population pharmacokinetics and trough of single and repeated doses in the pediatric population [ Time Frame: Continous ] [ Designated as safety issue: No ]
  • to determine the preliminary efficacy, including response rates, time to relapse and overall survival [ Time Frame: Continuous ] [ Designated as safety issue: No ]
  • to determine the presence and correlate baseline levels of activating mutations or WT-overexpression of the FLT3 gene in AMl and MLL rearranged ALL samples [ Time Frame: Predose, Day 3, and end of treatment ] [ Designated as safety issue: No ]
  • to evaluate changes in FLT3 phosphorylation following treatment, and correlate with changes in clinical outcome and pharmacokinetics [ Time Frame: Predose, Day 3, and end of treatment ] [ Designated as safety issue: No ]

Enrollment: 22
Study Start Date: September 2009
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Midostaurin Drug: midostaurin
Other Name: PKC412


Ages Eligible for Study:   3 Months to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00866281

United States, Washington
Seattle Children's Hospital CPKC412A2114
Seattle, Washington, United States, 98105
Novartis Investigative Site
Paris Cedex 19, France, 75935
Novartis Investigative Site
Genova, GE, Italy, 16147
Novartis Investigative Site
Monza, MB, Italy, 20900
Novartis Investigative Site
Roma, RM, Italy, 00165
Novartis Investigative Site
Torino, TO, Italy, 10126
Novartis Investigative Site
Rotterdam, Netherlands, 3015 GJ
Novartis Investigative Site
Stockholm, Sweden, SE-171 76
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00866281     History of Changes
Other Study ID Numbers: CPKC412A2114, 2008-006931-11
Study First Received: March 19, 2009
Last Updated: November 7, 2014
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: Ministry of Health
Netherlands: Ministry of Health, Welfare and Sport
Sweden: Medical Products Agency

Keywords provided by Novartis:
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Pediatric relapsed or refractory FLT3 positive Acute Myeloid Leukemia
Pediatric relapsed or refractory Mixed-lineage leukemia gene rearranged Acute Lymphoblastic leukemia

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2015