Back to resultsPKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinase 3 (FLT3) (CPKC412A2104E1 and CPKC412A2104E2)
Primary Purpose
Acute Myeloid Leukemia, Myelodysplastic Syndromes
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Itraconazole
PKC412
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring AML, MDS, high risk myelodysplastic syndrome
Eligibility Criteria
Inclusion criteria: Patients: with AML who are not candidates for myelosuppressive chemotherapy or with AML who have relapsed disease or are refractory to standard therapy and not likely to require cytoreductive therapy within one month or with MDS subtypes refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEB-T) or chronic myelomonocytic leukemia (CMML). Patients with a relevant FLT3-ITD mutation or D835Y point mutation Patients at least 18 years or older Patients with WHO performance status of 0 to 2 with a life expectancy of at least 3 months Patients must not be treated within 4 weeks after any prior therapy Written informed consent obtained according to local guidelines Exclusion criteria: Patients meeting any of the following criteria during screening will be excluded from entry into the study: Patients who had prior allogeneic, 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 gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PKC412.
Sites / Locations
- UCLA Medical Center
- Dana-Farber Cancer Institute
- New York Weill Cornell Medical Center
- Memorial Sloan Kettering Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
PKC412 (Core)
FLT3 mutated PKC412 100 mg/day (E1)
FLT3 mutated PKC412 200 mg/day (E1)
FLT3 wild type PKC412 100 mg/day (E1)
FLT3 wild type PKC412 200 mg/day (E1)
FLT3 mutated PKC412 dose escalation
FLT3 mutated PKC+Itraconazole (E2)
FLT3 wild type PKC412 dose escalation (E2)
FLT3 wild type PKC+Itraconazole (E2)
Arm Description
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
Outcomes
Primary Outcome Measures
Number of Participants With Best Clinical Response (Core)
Best clinical response was defined as complete response (CR) or partial response (PR), according to NCI definitions for AML and the guidelines for defining responses in MDS.
Percent Decrease in Phospho-FLT3 Compared to Baseline (Core)
Number of Participants With Overall Clinical Response (E1)
Overall clinical response was defined as CR, PR, minor response (MR) or blast response (BR). CR and PR was defined according to NCI definitions, and MR and BR was defined according to the guidelines for defining hematologic improvement in MDS.
Percent Decrease in Phospho-FLT3 Compared to Baseline (E1)
Percent Decrease in Phospho-FLT3 Compared to Baseline (E2)
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for PKC412 Plasma in the PKC + Itraconazole Combination Arm (E2)
Blood samples were collected for pharmacokinetic (PK) analysis.
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for PKC412 in the PKC + Itraconazole Combination Arm (E2)
Blood samples were collected for pharmacokinetic (PK) analysis.
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)
Blood samples were collected for PK analysis.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)
Blood samples were collected for PK analysis.
Terminal Elimination Half-life (T1/2) for PKC412 in the PKC + Itrconazole Combination Arm (E2)
Blood samples were collected for PK analysis.
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for CGP62221 Plasma in the PKC + Itraconazole Combination Arm (E2)
Blood samples were collected for pharmacokinetic (PK) analysis.
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP62221 in the PKC + Itraconazole Combination Arm (E2)
Blood samples were collected for pharmacokinetic (PK) analysis.
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP62221 in the PKC412 + Itraconazole Combination Arm (E2)
Blood samples were collected for PK analysis.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for CGP622221 in the PKC412 + Itraconazole Combination Arm (E2)
Blood samples were collected for PK analysis.
Terminal Elimination Half-life (T1/2) for CGP62221 in the PKC + Itrconazole Combination Arm (E2)
Blood samples were collected for PK analysis.
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for CGP52421 Plasma in the PKC + Itraconazole Combination Arm (E2)
Blood samples were collected for pharmacokinetic (PK) analysis.
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP52421 in the PKC + Itraconazole Combination Arm (E2)
Blood samples were collected for pharmacokinetic (PK) analysis.
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)
Blood samples were collected for PK analysis.
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)
Blood samples were collected for PK analysis.
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Blood samples were collected for analysis.
Summary of CGP62221 Concentration (E2)
Blood samples were collected for analysis.
Summary of CGP52421 Concentration (E2)
Blood samples were collected for analysis.
Secondary Outcome Measures
Time to Disease Progression (TTP) (Core)
TTP was defined as the time from first dose date to date of disease progression which is identified as study completion date for unsatisfactory treatment effect or date of death from any cause within the 28 day cutoff post treatment.
Summary of Midostaurin Plasma Concentration (Core)
Blood samples were collected for analysis.
Summary of CGP62221 Plasma Concentration (Core)
Blood samples were collected for analysis.
Summary of CGP52421 Plasma Concentration (Core)
Blood samples were collected for analysis.
Time to Disease Progression (E1)
TTP was defined as the time from the first dose date to the date of disease progression (defined as the study completion date for unsatisfactory treatment effect, date of response assessment of progressive disease, or date of death from any cause). One participant from the wild type 200 mg group did not have any assessment on treatment and therefore was not taken into account for TTP.
Overall Survival (OS) (E1)
OS was measured from the date of the first dose of treatment to the date of death from any cause or to the last date that the patient was known to be alive (a censored observation).
Duration of Best Clinical Response (E1)
Duration of best clinical response was measured from the time that the measurement criteria were met for CR, PR, MR (with or without blast reduction) or BR until the first date that recurrent disease was documented (event) or until the date of last follow up.
Event-free Survival (E1)
Event-free survival was defined as the time from date of start of treatment to the date of death from any cause, treatment failure or relapse
Summary of PKC412 Plasma Concentration for 50 mg Twice Daily (Bid) Arm (E1)
Blood samples were collected for analysis.
Summary of CGP62221 Plasma Concentration for 50 mg Bid Arm (E1)
Blood samples were collected for analysis.
Summary of CGP52421 Plasma Concentration for 50 mg Bid Arm (E1)
Blood samples were collected for analysis.
Summary of PKC412 Plasma Concentration for 100 mg Bid Arm (E1)
Blood samples were collected for analysis.
Summary of CGP62221 Plasma Concentration for 100 mg Bid Arm (E1)
Blood samples were collected for analysis.
Summary of CGP52421 Plasma Concentration for 100 mg Bid Arm (E1)
Blood samples were collected for analysis.
Best Clinical Response (E2)
Best clinical response was defined as CR, PR, MR, MR+BR, or BR . CR and PR was defined according to NCI definitions, and MR and BR was defined according to the guidelines for defining hematologic improvement in MDS.
Time to Disease Progression (E2)
TTP was defined as the time from the first dose date to the date of disease progression, which was defined as the study completion date for unsatisfactory treatment effect, the date of response assessment of progressive disease, or the date of death from any cause
Overall Survival (E2)
OS was measured from the date of the first dose of treatment to the date of death from any cause or the last date the patient was known to be alive (censored observation)
Full Information
NCT ID
NCT00045942
First Posted
September 16, 2002
Last Updated
August 7, 2017
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00045942
Brief Title
PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinase 3 (FLT3) (CPKC412A2104E1 and CPKC412A2104E2)
Official Title
An Open-label Phase II (Proof of Concept (POC)) Trial of PKC412 Monotherapy in Participants With Acute Myeloid Leukemia (AML) and Participants With High Risk Myelodysplastic Syndrome (MDS) (CPKC412A2104 Core); An Open-label, Randomized Phase II POC Trial in PKC412 in Participants With AML and Participants With High Risk MDS With Either Wild Type or Mutated FLT3 (CPKC412A2104E1); and An Open-label, Randomized Phase 1/II POC Trial in PKC412 in Participants With AML and Participants With High Risk MDS With Either Wild Type or Mutated FLT3 (CPKC412A2104E2)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
January 30, 2002 (Actual)
Primary Completion Date
March 27, 2008 (Actual)
Study Completion Date
March 27, 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
CPKC412A2104 core had a 2 stage design. In stage 1, eight participants were treated. If at least one participant showed a clinical response, four more participants were recruited to stage 2. The trial was to be stopped if no participants showed a response in stage 1. POC was achieved if at least 2 participants out of 12 responded. In PKC412A2104E1, participants with AML or high risk MDS with wild-type or mutant FTL3 who had not previously received a FLT3 inhibitor were randomized to receive continuous twice daily oral doses of either 50 or 100 mg midostaurin in 1 28-day cycle regimen. Participants were to be treated until disease progression or the occurrence of unacceptable treatment-related toxicity. PKC412A2104 E2 contained 2 dosing regimens: 1) intra-participant midostaurin dose escalation and 2) midostaurin with itraconazole in participants with AML and high risk MDS irrespective of FLT3 status. Eligible participants were alternately assigned to the regimens. At the Investigator's discretion, intra-participant dose escalation was allowed for any previously enrolled CPKC412A2104E1 participant receiving midostaurin at the time of the approval of amendment 4. Participants were treated until the time of disease progression.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, Myelodysplastic Syndromes
Keywords
AML, MDS, high risk myelodysplastic syndrome
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
144 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PKC412 (Core)
Arm Type
Experimental
Arm Description
Participants received 75 mg PKC412 three time daily (tid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
Arm Title
FLT3 mutated PKC412 100 mg/day (E1)
Arm Type
Experimental
Arm Description
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
Arm Title
FLT3 mutated PKC412 200 mg/day (E1)
Arm Type
Experimental
Arm Description
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
Arm Title
FLT3 wild type PKC412 100 mg/day (E1)
Arm Type
Experimental
Arm Description
Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
Arm Title
FLT3 wild type PKC412 200 mg/day (E1)
Arm Type
Experimental
Arm Description
Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
Arm Title
FLT3 mutated PKC412 dose escalation
Arm Type
Experimental
Arm Description
Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
Arm Title
FLT3 mutated PKC+Itraconazole (E2)
Arm Type
Experimental
Arm Description
Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
Arm Title
FLT3 wild type PKC412 dose escalation (E2)
Arm Type
Experimental
Arm Description
Participants were treated with PKC412 orally starting at a dose of 100 mg bid. A dose increase up to 300 mg bid was allowed. Participants were treated until time of disease progression, doubling of the bone marrow blast percentage from baseline, or the occurrence of unacceptable toxicity.
Arm Title
FLT3 wild type PKC+Itraconazole (E2)
Arm Type
Experimental
Arm Description
Within a cycle of 28 days, participants received a loading dose of PKC412 100 mg bid on days 1-2, followed by PKC412 50 mg bid for 3 weeks from days 3-21. On day 22, itraconazole 100 mg bid was added to the treatment regimen. The combinations of PKC412 and Itraconazole continued until disease progression, unacceptable toxicity, or withdrawal of consent.
Intervention Type
Drug
Intervention Name(s)
Itraconazole
Intervention Description
Itraconazole was commercially available.
Intervention Type
Drug
Intervention Name(s)
PKC412
Other Intervention Name(s)
Midostaurin
Intervention Description
PKC412 was supplied as soft gelatin capsules containing 25 mg PKC412.
Primary Outcome Measure Information:
Title
Number of Participants With Best Clinical Response (Core)
Description
Best clinical response was defined as complete response (CR) or partial response (PR), according to NCI definitions for AML and the guidelines for defining responses in MDS.
Time Frame
from date of first patient first visit (FPFV), 29-Jan-2002, to date of last participant last visit (LPLV), 04-Sep-2003
Title
Percent Decrease in Phospho-FLT3 Compared to Baseline (Core)
Time Frame
days 1, 28
Title
Number of Participants With Overall Clinical Response (E1)
Description
Overall clinical response was defined as CR, PR, minor response (MR) or blast response (BR). CR and PR was defined according to NCI definitions, and MR and BR was defined according to the guidelines for defining hematologic improvement in MDS.
Time Frame
from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004
Title
Percent Decrease in Phospho-FLT3 Compared to Baseline (E1)
Time Frame
days 1, 28
Title
Percent Decrease in Phospho-FLT3 Compared to Baseline (E2)
Time Frame
Days 1, 28
Title
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for PKC412 Plasma in the PKC + Itraconazole Combination Arm (E2)
Description
Blood samples were collected for pharmacokinetic (PK) analysis.
Time Frame
Cycle 1: days 21, 22, 28
Title
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for PKC412 in the PKC + Itraconazole Combination Arm (E2)
Description
Blood samples were collected for pharmacokinetic (PK) analysis.
Time Frame
Cycle 1: days 21, 22, 28
Title
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)
Description
Blood samples were collected for PK analysis.
Time Frame
Cycle 1: days 21, 22, 28
Title
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)
Description
Blood samples were collected for PK analysis.
Time Frame
Cycle 1: days 21, 22, 28
Title
Terminal Elimination Half-life (T1/2) for PKC412 in the PKC + Itrconazole Combination Arm (E2)
Description
Blood samples were collected for PK analysis.
Time Frame
Cycle 1: days 21 and 22
Title
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for CGP62221 Plasma in the PKC + Itraconazole Combination Arm (E2)
Description
Blood samples were collected for pharmacokinetic (PK) analysis.
Time Frame
Cycle 1: days 21, 22, 28
Title
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP62221 in the PKC + Itraconazole Combination Arm (E2)
Description
Blood samples were collected for pharmacokinetic (PK) analysis.
Time Frame
Cycle 1: days 21, 22, 28
Title
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP62221 in the PKC412 + Itraconazole Combination Arm (E2)
Description
Blood samples were collected for PK analysis.
Time Frame
Cycle 1: days 21, 22, 28
Title
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for CGP622221 in the PKC412 + Itraconazole Combination Arm (E2)
Description
Blood samples were collected for PK analysis.
Time Frame
Cycle 1: days 21, 22, 28
Title
Terminal Elimination Half-life (T1/2) for CGP62221 in the PKC + Itrconazole Combination Arm (E2)
Description
Blood samples were collected for PK analysis.
Time Frame
Cycle 1: day 22,
Title
Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval Tau (AUCtau) for CGP52421 Plasma in the PKC + Itraconazole Combination Arm (E2)
Description
Blood samples were collected for pharmacokinetic (PK) analysis.
Time Frame
Cycle 1: days 21, 22, 28
Title
Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP52421 in the PKC + Itraconazole Combination Arm (E2)
Description
Blood samples were collected for pharmacokinetic (PK) analysis.
Time Frame
Cycle 1: days 21, 22, 28
Title
Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)
Description
Blood samples were collected for PK analysis.
Time Frame
Cycle 1: days 21, 22, 28
Title
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUClast) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)
Description
Blood samples were collected for PK analysis.
Time Frame
Cycle 1: days 21, 22, 28
Title
Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)
Description
Blood samples were collected for analysis.
Time Frame
Cycle 1: days 1, 2 (24 hr post day 1), 3, 8, 15, 16 (24 hr post day 15), 17, 22; Cycle 2: days 1, 2 (24 hr post day 1), 3, 8, 15
Title
Summary of CGP62221 Concentration (E2)
Description
Blood samples were collected for analysis.
Time Frame
Cycle 1: days 1, 2 (24 hr post day 1), 3, 8, 15, 16 (24 hr post day 15), 17, 22; Cycle 2: days 1, 2 (24 hr post day 1), 3, 8, 15
Title
Summary of CGP52421 Concentration (E2)
Description
Blood samples were collected for analysis.
Time Frame
Cycle 1: days 1, 2 (24 hr post day 1), 3, 8, 15, 16 (24 hr post day 15), 17, 22; Cycle 2: days 1, 2 (24 hr post day 1), 3, 8, 15
Secondary Outcome Measure Information:
Title
Time to Disease Progression (TTP) (Core)
Description
TTP was defined as the time from first dose date to date of disease progression which is identified as study completion date for unsatisfactory treatment effect or date of death from any cause within the 28 day cutoff post treatment.
Time Frame
from date of FPFV, 29-Jan-2002, to date of LPLV, 04-Sep-2003
Title
Summary of Midostaurin Plasma Concentration (Core)
Description
Blood samples were collected for analysis.
Time Frame
Cycle 1: days 1 (24 hour), 3, 8; Cycle 2: day 1,
Title
Summary of CGP62221 Plasma Concentration (Core)
Description
Blood samples were collected for analysis.
Time Frame
Cycle 1: days 1 (24 hour), 3, 8; Cycle 2: day 1,
Title
Summary of CGP52421 Plasma Concentration (Core)
Description
Blood samples were collected for analysis.
Time Frame
Cycle 1: days 1 (24 hour), 3, 8; Cycle 2: day 1,
Title
Time to Disease Progression (E1)
Description
TTP was defined as the time from the first dose date to the date of disease progression (defined as the study completion date for unsatisfactory treatment effect, date of response assessment of progressive disease, or date of death from any cause). One participant from the wild type 200 mg group did not have any assessment on treatment and therefore was not taken into account for TTP.
Time Frame
from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004
Title
Overall Survival (OS) (E1)
Description
OS was measured from the date of the first dose of treatment to the date of death from any cause or to the last date that the patient was known to be alive (a censored observation).
Time Frame
from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004
Title
Duration of Best Clinical Response (E1)
Description
Duration of best clinical response was measured from the time that the measurement criteria were met for CR, PR, MR (with or without blast reduction) or BR until the first date that recurrent disease was documented (event) or until the date of last follow up.
Time Frame
from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004
Title
Event-free Survival (E1)
Description
Event-free survival was defined as the time from date of start of treatment to the date of death from any cause, treatment failure or relapse
Time Frame
from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004
Title
Summary of PKC412 Plasma Concentration for 50 mg Twice Daily (Bid) Arm (E1)
Description
Blood samples were collected for analysis.
Time Frame
Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h)
Title
Summary of CGP62221 Plasma Concentration for 50 mg Bid Arm (E1)
Description
Blood samples were collected for analysis.
Time Frame
Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h)
Title
Summary of CGP52421 Plasma Concentration for 50 mg Bid Arm (E1)
Description
Blood samples were collected for analysis.
Time Frame
Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h)
Title
Summary of PKC412 Plasma Concentration for 100 mg Bid Arm (E1)
Description
Blood samples were collected for analysis.
Time Frame
Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h); cycle 5: day 1 (0h) and cycle 6: day 1 (0h)
Title
Summary of CGP62221 Plasma Concentration for 100 mg Bid Arm (E1)
Description
Blood samples were collected for analysis.
Time Frame
Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h); cycle 5: day 1 (0h) and cycle 6: day 1 (0h)
Title
Summary of CGP52421 Plasma Concentration for 100 mg Bid Arm (E1)
Description
Blood samples were collected for analysis.
Time Frame
Cycle 1: days 1 (0h, 4h, 24 h), 3 (0h), 8 (0h); cycle 2: days 1 (0h); cycle 3: day 1 (0h); cycle 4: day 1 (0h); cycle 5: day 1 (0h) and cycle 6: day 1 (0h)
Title
Best Clinical Response (E2)
Description
Best clinical response was defined as CR, PR, MR, MR+BR, or BR . CR and PR was defined according to NCI definitions, and MR and BR was defined according to the guidelines for defining hematologic improvement in MDS.
Time Frame
date of FPFV, 21-Aug-2003, to date of LPLV, 27-Mar-2008
Title
Time to Disease Progression (E2)
Description
TTP was defined as the time from the first dose date to the date of disease progression, which was defined as the study completion date for unsatisfactory treatment effect, the date of response assessment of progressive disease, or the date of death from any cause
Time Frame
date of FPFV, 21-Aug-2003, to date of LPLV, 27-Mar-2008
Title
Overall Survival (E2)
Description
OS was measured from the date of the first dose of treatment to the date of death from any cause or the last date the patient was known to be alive (censored observation)
Time Frame
date of FPFV, 21-Aug-2003, to date of LPLV, 27-Mar-2008
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Patients:
with AML who are not candidates for myelosuppressive chemotherapy or with AML who have relapsed disease or are refractory to standard therapy and not likely to require cytoreductive therapy within one month or with MDS subtypes refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEB-T) or chronic myelomonocytic leukemia (CMML).
Patients with a relevant FLT3-ITD mutation or D835Y point mutation
Patients at least 18 years or older
Patients with WHO performance status of 0 to 2 with a life expectancy of at least 3 months
Patients must not be treated within 4 weeks after any prior therapy
Written informed consent obtained according to local guidelines
Exclusion criteria:
Patients meeting any of the following criteria during screening will be excluded from entry into the study:
Patients who had prior allogeneic, 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 gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PKC412.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
New York Weill Cornell Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome (CPKC412A2104 Core); and PKC412 in Participants With Acute Myeloid Leukemia or With Myelodysplastic Syndrome With Either Wild Type or Mutated FMS-like Tyrosine Kinase 3 (FLT3) (CPKC412A2104E1 and CPKC412A2104E2)
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