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Open-label Multicenter Study of PKC412 in Pts With AML and MDS With Either Wild-type or Mutated FLT3

This study has been completed.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals ) Identifier:
First received: September 15, 2009
Last updated: May 1, 2012
Last verified: May 2012
This study will assess the safety, tolerability, and pharmacokinetics in AML and high risk MDS patients with either wild type or mutated FLT3 using PKC412 with intra-patient dose escalation.

Condition Intervention Phase
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Drug: Midostaurin (PKC412)
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Phase I/II (Proof of Concept) Trial of PKC412 in Patients With Acute Myeloid Leukemia (AML) and Patients With High Risk Myelodysplastic Syndrome (MDS) With Either Wild Type or Mutated FLT3

Resource links provided by NLM:

Further study details as provided by Novartis:

Primary Outcome Measures:
  • Evaluate preliminary anti-tumor activity in AML and MDS patients with wild type or mutated FLT3 receiving continuous twice-daily oral dose of either 50 or 100 mg who have not previously received a FLT3 inhibitor. [ Time Frame: Day 28 of Cycle 2 ]
  • To determine the pharmacodynamic activity of PKC412 on functional FLT3 inhibition in the cells of these patients ex vivo [ Time Frame: Day 28 of Cycle 2 ]

Secondary Outcome Measures:
  • To evaluate the pharmacokinetics of PKC412 and its metabolites in peripheral blood WBC and saliva in order to assess the total and "free" concentration of PKC412 and its metabolites at two different twice daily orally administered doses of 50 and 100 mg [ Time Frame: D1, D2, D3 and D8 of Cycle 1 and D1 of each subsequent cycle ]

Enrollment: 95
Study Start Date: March 2003
Study Completion Date: October 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PKC412 50 mg BID, Wild Type FLT3 Drug: Midostaurin (PKC412)
Experimental: PKC412 100 mg BID, Wild Type FLT3 Drug: Midostaurin (PKC412)
Experimental: PKC412 50 mg BID, Mutant Type FLT3 Drug: Midostaurin (PKC412)
Experimental: PKC412 100 mg BID, Mutant Type FLT3 Drug: Midostaurin (PKC412)


Ages Eligible for Study:   14 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with AML who are not candidates for myelosuppressive chemotherapy or AML who have relapsed disease or refractory to standard therapy and not likely to require cytoreductive therapy within one month, or MDS subtypes RAEB, RAEB-T or CMML
  • Patients with a wild type or mutated FLT3 documented within 14 days prior to start of study who have not previously received a FLT3 inhibitor.
  • Patients with a WHO performance status of 0 to 2 with a life expectancy of at least 3 months

Exclusion Criteria:

  • Patients who had prior allergenic, syngeneic, or autologous bone marrow transplant or stem cell transplant less than 2 months previously.
  • Female patients who are pregnant or breast feeding or adults of childbearing age not employing an effective method of birth control
  • Concurrent severe and/or uncontrolled medical or psychiatric condition which may interfere with the completion of the study
  • Impairment of GI function or GI disease that may significant alter the absorption of PKC412
  • Patients who had more than 2 prior regimens for their current relapsed or current primary refractory disease.
  • Uncontrolled active infection

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
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Please refer to this study by its identifier: NCT00977782

United States, Massachusetts
Dana Faber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Cornell Comprehensive Cancer Center
New York, New York, United States, 10065
Memorial Slon-Kettering Cancer Center
New York, New York, United States, 10065
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Novartis Investigative Site
Dresden, Germany
Novartis Investigative Site
Mainz, Germany
Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals Identifier: NCT00977782     History of Changes
Other Study ID Numbers: CPKC412A2104E1
Study First Received: September 15, 2009
Last Updated: May 1, 2012

Keywords provided by Novartis:
wild type FLT3
mutated FLT3

Additional relevant MeSH terms:
Leukemia, Myeloid
Myelodysplastic Syndromes
Leukemia, Myeloid, Acute
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on April 25, 2017