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

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00977782
• Other study ID #: CPKC412A2104E1
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 15, 2009
• Last updated: May 1, 2012
• Start date: March 2003
• Est. completion date: October 2008

Study information

• Verified date: May 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationGermany: Bundesinstitut für Arzneimittel und Medizinprodukte
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: October 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 14 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• Midostaurin (PKC412)

Locations

Country	Name	City	State
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Mainz
United States	Dana Faber Cancer Institute	Boston	Massachusetts
United States	MD Anderson Cancer Center	Houston	Texas
United States	Cornell Comprehensive Cancer Center	New York	New York
United States	Memorial Slon-Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		Day 28 of Cycle 2	Yes
Primary	To determine the pharmacodynamic activity of PKC412 on functional FLT3 inhibition in the cells of these patients ex vivo		Day 28 of Cycle 2	Yes
Secondary	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		D1, D2, D3 and D8 of Cycle 1 and D1 of each subsequent cycle	Yes