This site became the new ClinicalTrials.gov on June 19th. Learn more.
Show more
ClinicalTrials.gov Menu IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu IMPORTANT: Talk with a trusted healthcare professional before volunteering for a study. Read more...
ClinicalTrials.gov Menu
Give us feedback

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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00045942
First received: September 16, 2002
Last updated: August 7, 2017
Last verified: August 2017
Results First Received: May 3, 2017  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndromes
Interventions: Drug: Itraconazole
Drug: PKC412

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
In PKC412A2104 (Core), FLT3 mutated participants with AML or MDS received open-label PKC412. In PKC412A2104E1, FLT3 mutated participants and FLT3 wild type participants were randomized to receive either PKC412 50 mg bid or PKC412 100 mg bid.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
In PKC412A2104E2, participants were alternately assigned to the regimens, beginning with the first enrolled into the intra-patient dose escalation arm and the next enrolled into the PKC412 + itraconazole arm. Of the 16 participants enrolled in the PKC412 dose escalation arm, 14 were newly enrolled, and 2 were transitioned from PKC412A2104E1.

Reporting Groups
  Description
PKC412 in FLT3 Mutated Participants (Core) 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.
FLT3 Mutated PKC412 100 mg/Day (E1) Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
FLT3 Mutated PKC412 200 mg/Day (E1) Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
FLT3 Wild Type PKC412 100 mg/Day (E1) Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
FLT3 Wild Type PKC412 200 mg/Day (E1) Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
FLT3 Mutated PKC412 Dose Escalation (E2) 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.
FLT3 Mutated PKC+Itraconazole (E2) 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.
FLT3 Wild Type PKC412 Dose Escalation (E2) 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.
FLT3 Wild Type PKC+Itraconazole (E2) 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.

Participant Flow for 3 periods

Period 1:   PKC412A2104 (Core)
    PKC412 in FLT3 Mutated Participants (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 (E2)   FLT3 Mutated PKC+Itraconazole (E2)   FLT3 Wild Type PKC412 Dose Escalation (E2)   FLT3 Wild Type PKC+Itraconazole (E2)
STARTED   20   0   0   0   0   0   0   0   0 
Core Primary Efficacy   20   0   0   0   0   0   0   0   0 
COMPLETED   0   0   0   0   0   0   0   0   0 
NOT COMPLETED   20   0   0   0   0   0   0   0   0 
Withdrawal by Subject                1                0                0                0                0                0                0                0                0 
Adverse Event                5                0                0                0                0                0                0                0                0 
Lack of Efficacy                13                0                0                0                0                0                0                0                0 
Death                1                0                0                0                0                0                0                0                0 

Period 2:   PKC412A2104E1
    PKC412 in FLT3 Mutated Participants (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 (E2)   FLT3 Mutated PKC+Itraconazole (E2)   FLT3 Wild Type PKC412 Dose Escalation (E2)   FLT3 Wild Type PKC+Itraconazole (E2)
STARTED   0   18   17   33   27   0   0   0   0 
Primary Efficacy   0   18   17   32   25   0   0   0   0 
COMPLETED   0   0   0   0   0   0   0   0   0 
NOT COMPLETED   0   18   17   33   27   0   0   0   0 
Withdrawal by Subject                0                0                2                5                2                0                0                0                0 
Condition no longer requires study drug                0                1                1                0                1                0                0                0                0 
Lack of Efficacy                0                11                11                23                17                0                0                0                0 
Abnormal laboratory value                0                1                0                0                0                0                0                0                0 
Adverse Event                0                1                1                3                6                0                0                0                0 
Death                0                4                1                1                1                0                0                0                0 
Enrolled into PKC412A2104E2                0                0                1                1                0                0                0                0                0 

Period 3:   PKC412A2104E2
    PKC412 in FLT3 Mutated Participants (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 (E2)   FLT3 Mutated PKC+Itraconazole (E2)   FLT3 Wild Type PKC412 Dose Escalation (E2)   FLT3 Wild Type PKC+Itraconazole (E2)
STARTED   0   0   0   0   0   9   7   7   6 
Primary Efficacy   0   0   0   0   0   9   7   7   6 
COMPLETED   0   0   0   0   0   0   0   0   0 
NOT COMPLETED   0   0   0   0   0   9   7   7   6 
Lost to Follow-up                0                0                0                0                0                0                0                3                0 
Withdrawal by Subject                0                0                0                0                0                1                0                1                0 
Lack of Efficacy                0                0                0                0                0                3                2                2                6 
Adverse Event                0                0                0                0                0                4                3                1                0 
Death                0                0                0                0                0                1                2                0                0 



  Baseline Characteristics
  Hide Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The baseline characteristics for PKC412A2104E2 do not include data for the 2 patients who transferred from CPKC412A2104E1 since the data for these 2 patients are included under CPKC412A2104E1.

Reporting Groups
  Description
PKC412 in FLT3 Mutated Participants (Core) 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.
FLT3 Mutated PKC412 100 mg/Day (E1) Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
FLT3 Mutated PKC412 200 mg/Day (E1) Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
FLT3 Wild Type PKC412 100 mg/Day (E1) Participants received 50 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
FLT3 Wild Type PKC412 200 mg/Day (E1) Participants received 100 mg PKC412 twice daily (bid) orally on a continuous basis until disease progression or the occurrence of unacceptable treatment related toxicity.
FLT3 Mutated PKC412 Dose Escalation (E2) 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.
FLT3 Mutated PKC+Itraconazole (E2) 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.
FLT3 Wild Type PKC412 Dose Escalation (E2) 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.
FLT3 Wild Type PKC+Itraconazole (E2) 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.
Total Total of all reporting groups

Baseline Measures
   PKC412 in FLT3 Mutated Participants (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 (E2)   FLT3 Mutated PKC+Itraconazole (E2)   FLT3 Wild Type PKC412 Dose Escalation (E2)   FLT3 Wild Type PKC+Itraconazole (E2)   Total 
Overall Participants Analyzed 
[Units: Participants]
 20   18   17   33   27   8   7   6   6   142 
Age 
[Units: Participants]
Count of Participants
                   
<=18 years      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0%      0   0.0% 
Between 18 and 65 years      11  55.0%      11  61.1%      8  47.1%      7  21.2%      8  29.6%      6  75.0%      5  71.4%      0   0.0%      0   0.0%      56  39.4% 
>=65 years      9  45.0%      7  38.9%      9  52.9%      26  78.8%      19  70.4%      2  25.0%      2  28.6%      6 100.0%      6 100.0%      86  60.6% 
Sex: Female, Male 
[Units: Participants]
Count of Participants
                   
Female      6  30.0%      5  27.8%      9  52.9%      17  51.5%      15  55.6%      3  37.5%      3  42.9%      4  66.7%      4  66.7%      66  46.5% 
Male      14  70.0%      13  72.2%      8  47.1%      16  48.5%      12  44.4%      5  62.5%      4  57.1%      2  33.3%      2  33.3%      76  53.5% 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Best Clinical Response (Core)   [ Time Frame: from date of first patient first visit (FPFV), 29-Jan-2002, to date of last participant last visit (LPLV), 04-Sep-2003 ]

2.  Primary:   Percent Decrease in Phospho-FLT3 Compared to Baseline (Core)   [ Time Frame: days 1, 28 ]

3.  Primary:   Number of Participants With Overall Clinical Response (E1)   [ Time Frame: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004 ]

4.  Primary:   Percent Decrease in Phospho-FLT3 Compared to Baseline (E1)   [ Time Frame: days 1, 28 ]

5.  Primary:   Percent Decrease in Phospho-FLT3 Compared to Baseline (E2)   [ Time Frame: Days 1, 28 ]

6.  Primary:   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)   [ Time Frame: Cycle 1: days 21, 22, 28 ]

7.  Primary:   Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for PKC412 in the PKC + Itraconazole Combination Arm (E2)   [ Time Frame: Cycle 1: days 21, 22, 28 ]

8.  Primary:   Time to Reach the Maximum Concentration After Drug Administration (Tmax) for PKC412 in the PKC412 + Itraconazole Combination Arm (E2)   [ Time Frame: Cycle 1: days 21, 22, 28 ]

9.  Primary:   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)   [ Time Frame: Cycle 1: days 21, 22, 28 ]

10.  Primary:   Terminal Elimination Half-life (T1/2) for PKC412 in the PKC + Itrconazole Combination Arm (E2)   [ Time Frame: Cycle 1: days 21 and 22 ]

11.  Primary:   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)   [ Time Frame: Cycle 1: days 21, 22, 28 ]

12.  Primary:   Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP62221 in the PKC + Itraconazole Combination Arm (E2)   [ Time Frame: Cycle 1: days 21, 22, 28 ]

13.  Primary:   Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP62221 in the PKC412 + Itraconazole Combination Arm (E2)   [ Time Frame: Cycle 1: days 21, 22, 28 ]

14.  Primary:   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)   [ Time Frame: Cycle 1: days 21, 22, 28 ]

15.  Primary:   Terminal Elimination Half-life (T1/2) for CGP62221 in the PKC + Itrconazole Combination Arm (E2)   [ Time Frame: Cycle 1: day 22, ]

16.  Primary:   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)   [ Time Frame: Cycle 1: days 21, 22, 28 ]

17.  Primary:   Observed Maximum Plasma Concentration Following Drug Administration at Steady State (Cmax) for CGP52421 in the PKC + Itraconazole Combination Arm (E2)   [ Time Frame: Cycle 1: days 21, 22, 28 ]

18.  Primary:   Time to Reach the Maximum Concentration After Drug Administration (Tmax) for CGP52421 in the PKC412 + Itraconazole Combination Arm (E2)   [ Time Frame: Cycle 1: days 21, 22, 28 ]

19.  Primary:   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)   [ Time Frame: Cycle 1: days 21, 22, 28 ]

20.  Primary:   Summary of Midostaurin Concentration in the PKC412 Dose Escalation Arms(E2)   [ 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 ]

21.  Primary:   Summary of CGP62221 Concentration (E2)   [ 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 ]

22.  Primary:   Summary of CGP52421 Concentration (E2)   [ 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 ]

23.  Secondary:   Time to Disease Progression (TTP) (Core)   [ Time Frame: from date of FPFV, 29-Jan-2002, to date of LPLV, 04-Sep-2003 ]

24.  Secondary:   Summary of Midostaurin Plasma Concentration (Core)   [ Time Frame: Cycle 1: days 1 (24 hour), 3, 8; Cycle 2: day 1, ]

25.  Secondary:   Summary of CGP62221 Plasma Concentration (Core)   [ Time Frame: Cycle 1: days 1 (24 hour), 3, 8; Cycle 2: day 1, ]

26.  Secondary:   Summary of CGP52421 Plasma Concentration (Core)   [ Time Frame: Cycle 1: days 1 (24 hour), 3, 8; Cycle 2: day 1, ]

27.  Secondary:   Time to Disease Progression (E1)   [ Time Frame: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004 ]

28.  Secondary:   Overall Survival (OS) (E1)   [ Time Frame: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004 ]

29.  Secondary:   Duration of Best Clinical Response (E1)   [ Time Frame: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004 ]

30.  Secondary:   Event-free Survival (E1)   [ Time Frame: from date of FPFV, 27-Mar-2003, to date of LPLV, 06-Sep-2004 ]

31.  Secondary:   Summary of PKC412 Plasma Concentration for 50 mg Twice Daily (Bid) Arm (E1)   [ 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) ]

32.  Secondary:   Summary of CGP62221 Plasma Concentration for 50 mg Bid Arm (E1)   [ 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) ]

33.  Secondary:   Summary of CGP52421 Plasma Concentration for 50 mg Bid Arm (E1)   [ 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) ]

34.  Secondary:   Summary of PKC412 Plasma Concentration for 100 mg Bid Arm (E1)   [ 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) ]

35.  Secondary:   Summary of CGP62221 Plasma Concentration for 100 mg Bid Arm (E1)   [ 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) ]

36.  Secondary:   Summary of CGP52421 Plasma Concentration for 100 mg Bid Arm (E1)   [ 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) ]

37.  Secondary:   Best Clinical Response (E2)   [ Time Frame: date of FPFV, 21-Aug-2003, to date of LPLV, 27-Mar-2008 ]

38.  Secondary:   Time to Disease Progression (E2)   [ Time Frame: date of FPFV, 21-Aug-2003, to date of LPLV, 27-Mar-2008 ]

39.  Secondary:   Overall Survival (E2)   [ Time Frame: date of FPFV, 21-Aug-2003, to date of LPLV, 27-Mar-2008 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
  Hide More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis
phone: 862-778-8300



Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00045942     History of Changes
Obsolete Identifiers: NCT00045578, NCT00977782
Other Study ID Numbers: CPKC412A2104
Study First Received: September 16, 2002
Results First Received: May 3, 2017
Last Updated: August 7, 2017