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:
Novartis Pharmaceuticals
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
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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
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 | |
| Memorial Slon-Kettering Cancer Center | |
| New York, New York, United States, 10065 | |
| Cornell Comprehensive 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, Acute Leukemia, Myeloid Myelodysplastic Syndromes Preleukemia Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases |
Hematologic Diseases Precancerous Conditions 4'-N-benzoylstaurosporine Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 23, 2013