A Study of the Safety and Preliminary Efficacy of Oral Midostaurin (PKC412) in Relapsed or Refractory Pediatric Leukemia
This study is currently recruiting participants.
Verified March 2013 by Novartis
Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00866281
First received: March 19, 2009
Last updated: March 22, 2013
Last verified: March 2013
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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 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | 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 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 Study Completion Date: | November 2013 |
| Estimated Primary Completion Date: | April 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Midostaurin |
Drug: midostaurin
Other Name: PKC412
|
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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00866281
Contacts
| Contact: Novartis Pharmaceuticals | 1-888-669-6682 | |
| Contact: Novartis Pharmaceuticals |
Locations
| United States, California | |
| Children's Hospital of Orange County CHOC Cancer Institute | Recruiting |
| Orange, California, United States, 92868-3874 | |
| Contact: Cheryl Willis 714-532-8824 cwillis@choc.org | |
| Principal Investigator: Steven Neudorf | |
| United States, Colorado | |
| University of Colorado Children's Hospital Colorado | Withdrawn |
| Aurora, Colorado, United States, 80045 | |
| United States, Illinois | |
| Ann & Robert H. Lurie Children's Hospital of Chicago SC | Recruiting |
| Chicago, Illinois, United States, 60611 | |
| Contact: Jill Woodman 312-227-4860 jwoodman@luriechildrens.org | |
| Principal Investigator: Nobuko Hijiya | |
| United States, Massachusetts | |
| Dana Farber Cancer Institute Deptof DanaFarberCancerInst(4) | Recruiting |
| Boston, Massachusetts, United States, 02115 | |
| Contact: Kristie Lee Stolgitis +1 617 632 6191 kstolgitis@partners.org | |
| Principal Investigator: Lewis B Silverman | |
| United States, Washington | |
| Seattle Children's Hospital CPKC412A2114 | Recruiting |
| Seattle, Washington, United States, 98105 | |
| Contact: Jayme Ribaudo 206-884-1214 jayme.ribaudo@seattlechildrens.org | |
| Principal Investigator: Blythe Thomson | |
| France | |
| Novartis Investigative Site | Recruiting |
| Lyon Cedex 08, France, 69373 | |
| Novartis Investigative Site | Recruiting |
| Paris, France, 75475 | |
| Italy | |
| Novartis Investigative Site | Recruiting |
| Genova, GE, Italy, 16147 | |
| Novartis Investigative Site | Recruiting |
| Monza, MB, Italy, 20900 | |
| Novartis Investigative Site | Recruiting |
| Roma, RM, Italy, 00165 | |
| Novartis Investigative Site | Recruiting |
| Torino, TO, Italy, 10126 | |
| Netherlands | |
| Novartis Investigative Site | Active, not recruiting |
| Rotterdam, Netherlands, 3015 GJ | |
| Sweden | |
| Novartis Investigative Site | Recruiting |
| Stockholm, Sweden, SE-171 76 | |
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| 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: | March 22, 2013 |
| 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 |
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 Leukemia, Lymphoid Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Myeloid, Acute Leukemia, Myeloid Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases |
Immunoproliferative Disorders Immune System Diseases 4'-N-benzoylstaurosporine Staurosporine Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 16, 2013