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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00977782
First received: September 15, 2009
Last updated: May 1, 2012
Last verified: May 2012
  Purpose

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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: Yes ]

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)

  Eligibility

Ages Eligible for Study:   14 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
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: NCT00977782

Locations
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
Germany
Novartis Investigative Site
Dresden, Germany
Novartis Investigative Site
Mainz, Germany
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: NCT00977782     History of Changes
Other Study ID Numbers: CPKC412A2104E1
Study First Received: September 15, 2009
Last Updated: May 1, 2012
Health Authority: United States: Food and Drug Administration
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte

Keywords provided by Novartis:
Leukemia
AML
MDS
FLT3
midostaurin
wild type FLT3
mutated FLT3

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
4'-N-benzoylstaurosporine
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014