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Trial record 2 of 3 for:    windreich

Pharmacokinetics-based Mycophenolate Mofetil Dosing for GVHD Prevention

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ClinicalTrials.gov Identifier: NCT01487577
Recruitment Status : Completed
First Posted : December 7, 2011
Results First Posted : June 21, 2016
Last Update Posted : June 21, 2016
Sponsor:
Information provided by (Responsible Party):
Randy Windreich, University of Pittsburgh

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Allogeneic Blood and Marrow Transplantation (BMT)
Graft Versus Host Disease
Intervention Drug: Mycophenolate mofetil
Enrollment 19

Recruitment Details Candidates are identified through the investigators' clinical practice.
Pre-assignment Details  
Arm/Group Title Mycophenolate Mofetil
Hide Arm/Group Description Pharmacokinetics-based targeting of Mycophenolate mofetil
Period Title: Overall Study
Started 19
Completed 18 [1]
Not Completed 1
Reason Not Completed
Became ineligible after signing consent             1
[1]
One participant became ineligible after signing consent, but before receiving protocol therapy.
Arm/Group Title Mycophenolate Mofetil
Hide Arm/Group Description

Pharmacokinetics-based targeting of mycophenolate mofetil

Mycophenolate mofetil: Based on individual pharmacokinetics data, mycophenolate mofetil will be administered by continuous infusion to target a desired AUC exposure

Overall Number of Baseline Participants 19
Hide Baseline Analysis Population Description
Pediatric hematopoietic stem cell recipients undergoing myeloablative conditioning therapy
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
<=18 years
16
  84.2%
Between 18 and 65 years
3
  15.8%
>=65 years
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
Female
10
  52.6%
Male
9
  47.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 19 participants
American Indian or Alaska Native
0
   0.0%
Asian
2
  10.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   5.3%
White
15
  78.9%
More than one race
1
   5.3%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 19 participants
19
1.Primary Outcome
Title Number of Participants With Grade ≥3 Toxicities Scored According to the CTCAE Version 4.0.
Hide Description [Not Specified]
Time Frame 100 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mycophenolate Mofetil
Hide Arm/Group Description:

Pharmacokinetics-based targeting of mycophenolate mofetil

Mycophenolate mofetil: Based on individual pharmacokinetics data, mycophenolate mofetil will be administered by continuous infusion to target a desired AUC exposure

Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: participants
0
2.Primary Outcome
Title Number of Participants With Acute Grade II-IV GVHD, Acute Grade III-IV GVHD, and Chronic GVHD.
Hide Description Acute GVHD will be graded according to the Modified Glucksberg Staging Criteria. Chronic GVHD will be graded according to NIH Chronic GVHD Consensus Guidelines.
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mycophenolate Mofetil
Hide Arm/Group Description:

Pharmacokinetics-based targeting of mycophenolate mofetil

Mycophenolate mofetil: Based on individual pharmacokinetics data, mycophenolate mofetil will be administered by continuous infusion to target a desired AUC exposure

Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: participants
Acute grade II-IV GVHD 6
Acute grade III-IV GVHD 4
Chronic GVHD 2
3.Secondary Outcome
Title Number of Participants With Neutrophil and Platelet Engraftment.
Hide Description Neutrophil and platelet engraftment definitions as defined by the CIBMTR Data Management Manual.
Time Frame 100 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mycophenolate Mofetil
Hide Arm/Group Description:

Pharmacokinetics-based targeting of mycophenolate mofetil

Mycophenolate mofetil: Based on individual pharmacokinetics data, mycophenolate mofetil will be administered by continuous infusion to target a desired AUC exposure

Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: participants
Incidence of neutrophil engraftment 18
Incidence of platelet engraftment 15
4.Secondary Outcome
Title Number of Participants Who Experienced Relapse.
Hide Description [Not Specified]
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mycophenolate Mofetil
Hide Arm/Group Description:

Pharmacokinetics-based targeting of mycophenolate mofetil

Mycophenolate mofetil: Based on individual pharmacokinetics data, mycophenolate mofetil will be administered by continuous infusion to target a desired AUC exposure

Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: participants
4
5.Secondary Outcome
Title Number of Participants Who Experienced Nonrelapse Mortality.
Hide Description [Not Specified]
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mycophenolate Mofetil
Hide Arm/Group Description:

Pharmacokinetics-based targeting of mycophenolate mofetil

Mycophenolate mofetil: Based on individual pharmacokinetics data, mycophenolate mofetil will be administered by continuous infusion to target a desired AUC exposure

Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: participants
0
6.Secondary Outcome
Title Number of Participants in Overall Survival.
Hide Description [Not Specified]
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mycophenolate Mofetil
Hide Arm/Group Description:

Pharmacokinetics-based targeting of mycophenolate mofetil

Mycophenolate mofetil: Based on individual pharmacokinetics data, mycophenolate mofetil will be administered by continuous infusion to target a desired AUC exposure

Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: participants
15
7.Secondary Outcome
Title Pharmacokinetic Analysis of MMF AUC to Evaluate MMF Dose Relationships to Drug Exposure.
Hide Description Pharmacokinetic analysis includes, but is not limited to, area under the plasma concentration versus time curve (AUC).
Time Frame 100 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mycophenolate Mofetil
Hide Arm/Group Description:

Pharmacokinetics-based targeting of mycophenolate mofetil

Mycophenolate mofetil: Based on individual pharmacokinetics data, mycophenolate mofetil will be administered by continuous infusion to target a desired AUC exposure

Overall Number of Participants Analyzed 18
Median (Full Range)
Unit of Measure: mcg*hr/mL
AUC, Intermittent IV dosing
46.5
(16.7 to 65.9)
AUC, Continuous infusion
40.1
(20.6 to 63.8)
AUC, Intermittent PO dosing
36.1
(11.9 to 95.9)
8.Secondary Outcome
Title Pharmacokinetic Analysis of MMF Clearance to Evaluate MMF Dose Relationships to Drug Exposure.
Hide Description Pharmacokinetic analysis includes, but is not limited to, clearance.
Time Frame 100 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mycophenolate Mofetil
Hide Arm/Group Description:

Pharmacokinetics-based targeting of mycophenolate mofetil

Mycophenolate mofetil: Based on individual pharmacokinetics data, mycophenolate mofetil will be administered by continuous infusion to target a desired AUC exposure

Overall Number of Participants Analyzed 18
Median (Full Range)
Unit of Measure: mL/min/kg
Clearance, Intermittent IV dosing
10.2
(6.8 to 30.8)
Clearance, Continuous infusion
15.1
(7.2 to 73)
Clearance, Intermittent PO dosing
10.9
(4.9 to 26.6)
9.Secondary Outcome
Title Pharmacokinetic Analysis of MMF Steady State Concentration to Evaluate MMF Dose Relationships to Drug Exposure.
Hide Description Pharmacokinetic analysis includes, but is not limited to, steady-state concentrations.
Time Frame 100 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Mycophenolate Mofetil
Hide Arm/Group Description:

Pharmacokinetics-based targeting of mycophenolate mofetil

Mycophenolate mofetil: Based on individual pharmacokinetics data, mycophenolate mofetil will be administered by continuous infusion to target a desired AUC exposure

Overall Number of Participants Analyzed 18
Median (Full Range)
Unit of Measure: mcg/mL
Steady-state concentration, Intermittent IV dosing
1.9
(0.6 to 2.7)
Steady-state concentration, Continuous infusion
1.7
(0.9 to 2.7)
Steady-state concentration, Intermittent PO dosing
1.5
(0.5 to 4.0)
Time Frame 1 year post-enrollment
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Mycophenolate Mofetil
Hide Arm/Group Description

Pharmacokinetics-based targeting of mycophenolate mofetil

Mycophenolate mofetil: Based on individual pharmacokinetics data, mycophenolate mofetil will be administered by continuous infusion to target a desired AUC exposure

All-Cause Mortality
Mycophenolate Mofetil
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Mycophenolate Mofetil
Affected / at Risk (%) # Events
Total   4/18 (22.22%)    
Cardiac disorders   
Pericardial effusion * 1 [1]  1/18 (5.56%)  1
Hepatobiliary disorders   
Hepatobiliary disorders, other * 1 [2]  2/18 (11.11%)  2
Infections and infestations   
Tracheitis * 1 [3]  1/18 (5.56%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
[1]
Aseptic pericardial effusion
[2]
Veno-occlusive disease of the liver
[3]
Laryngotracheitis due to HSV
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Mycophenolate Mofetil
Affected / at Risk (%) # Events
Total   8/18 (44.44%)    
Immune system disorders   
Acute GVHD * 1  8/18 (44.44%)  8
Chronic GVHD * 1  2/18 (11.11%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Our study is limited by small sample size and heterogeneity in stem cell sources. Besides targeted MMF dosing, other factors that might have affected clinical outcomes include duration of MMF and use of ATG in unrelated-donor transplants.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Randy M. Windreich, MD
Organization: Children's Hospital of Pittsburgh of UPMC
Phone: 412-692-5225
Responsible Party: Randy Windreich, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01487577     History of Changes
Other Study ID Numbers: CHP_BMT_MMF_10
First Submitted: November 23, 2011
First Posted: December 7, 2011
Results First Submitted: February 24, 2016
Results First Posted: June 21, 2016
Last Update Posted: June 21, 2016