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

Sponsor:	Novartis Pharmaceuticals
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00866281

Purpose

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 I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment
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:

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Cgp 41251

U.S. FDA Resources

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 7 days 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 ]

Estimated Enrollment:	22
Study Start Date:	September 2009
Estimated Primary Completion Date:	March 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Midostaurin: Experimental	Drug: midostaurin

Eligibility

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

Criteria

Inclusion Criteria:

Mixed-lineage leukemia (MLL) gene rearranged Acute Lympoblastic 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

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

Contacts

Contact: Novartis Pharmaceuticals

+1 800 340 6843

Locations

United States, Massachusetts
Dana Faber Cancer Institute, Children's Hospital, Dept. of Pediatric Oncology	Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Jane E. O'Brien, CCRP 617-632-3549 jane_obrien@dfci.harvard.edu
Principal Investigator: Lewis Silverman, M.D.
United States, Washington
Seattle Children's Hospital	Not yet recruiting
Seattle, Washington, United States, 98105
Contact: Sara Muchinsky 206-884-1591 Sara.muchinsky@seattlechildrens.org
Principal Investigator: Blythe Thomson, M.D.
France
Novartis Investigative Site	Not yet recruiting
Paris, France
Novartis Investigative Site	Not yet recruiting
Lyon, France
Italy
Novartis Investigative Site	Not yet recruiting
Monza, Italy
Novartis Investigative Site	Not yet recruiting
Torino, Italy
Novartis Investigative Site	Not yet recruiting
Genova, Italy
Novartis Investigative Site	Not yet recruiting
Rome, Italy
Netherlands
Novartis Investigative Site	Not yet recruiting
Rotterdam, Netherlands
Sweden
Novartis Investigative Site	Recruiting
Stockholm, Sweden

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis Pharmaceuticals ( External Affairs )
Study ID Numbers:	CPKC412A2114, EudraCT number 2008-006931-11
Study First Received:	March 19, 2009
Last Updated:	November 18, 2009
ClinicalTrials.gov Identifier:	NCT00866281 History of Changes
Health Authority:	United States: Food and Drug Administration; France: Afssaps - French Health Products Safety Agency; Italy: Ministry of Health; Netherlands: Ministry of Health, Welfare and Sport

Keywords provided by Novartis:

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

Additional relevant MeSH terms:

Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Immunoproliferative Disorders
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Enzyme Inhibitors
Leukemia, Myeloid

Leukemia, Myeloid, Acute
4'-N-benzoylstaurosporine
Pharmacologic Actions
Leukemia
Lymphatic Diseases
Neoplasms
Therapeutic Uses
Lymphoproliferative Disorders

ClinicalTrials.gov processed this record on February 08, 2010