Frontiers

From Bench to Bedside 2013 

Tags:

OSU-11055:  Model development to personalize dosing for intravenous melphalan in the setting of autologous transplant for multiple myelomaOSU-11055:  Model development to personalize dosing for intravenous melphalan in the setting of autologous transplant for multiple myeloma

HYPOTHESIS: Our pharmacokinetic model will predict interpatient variability; melphalan drug exposure will correlate with mucositis and duration of neutropenia; and measurements of DNA damage using patient blood in the laboratory will be directly related to melphalan concentrations, thereby allowing for the creation of a model that will be the first of its kind to personalize chemotherapy dosing in the setting of an autologous hematopoietic stem-cell transplant.

RATIONALE: In multiple myeloma, one of the most effective therapies is the use of high-dose intravenous (IV) melphalan, which is given at either 140 or 200 mg/m2 as an IV bolus followed by autologous stem cell rescue 48 hours after infusion—in the United States we perform more than 5,000 myeloma transplants yearly.  Autologous transplant is associated with severe toxicity (1-5 percent transplant-related mortality), a 16-day inpatient stay on average, and a quality of life decrement that lasts nine months on average. There have been no improvements in the basics of autologous transplant for myeloma in the last 20 years because there is extensive interpatient variability in melphalan exposure, and no adequate PK/PD model has been developed.
  
    The No. 1 patient complaint with autologous transplant for myeloma used to be mucositis before the use at Ohio State of oral cryotherapy. Standard ice-chip therapy requires patients to hold one ounce of ice chips in their mouth, then replenishing them when melted, for 30 minutes before and during, and continuously for six hours after melphalan infusion (seven hours total).  Prolonged ice-chip therapy is a hardship for patients.

    In the setting of an ongoing randomized controlled trial of myeloma patients undergoing autologous transplant comparing the incidence of severe mucositis in two-hour versus six-hour schedules of crushed ice therapy, we are gathering relevant pharmacokinetic data, performing experiments using patients’ peripheral blood mononuclear cells (PBMCs) to measure DNA damage (primarily accumulation of p53 protein) with different concentrations of melphalan, and monitoring patients closely for melphalan-related toxicities.  The objective is to develop a model that will include covariates that are clinical (mucositis grade, neutropenia duration), pharmacokinetic (melphalan exposure and maximum serum concentration), and pharmacodynamic (ex vivo DNA damage) to predict the optimal dose of melphalan.  With completion of this study, we will have developed a model that will be validated in a multicenter prospective trial.

AT A GLANCE
Trial no.: OSU-11055 (ClinicalTrials.gov identifier: NCT01653106)

PI: Craig Hofmeister, MD, MPH

Phone: 614-293-7807

Email: craig.hofmeister@osumc.edu

Eligibility: Patients must be diagnosed with multiple myeloma and admitted for autologous stem cell transplantation; Age: 18 years or older; Ability to read and understand informed consent.

 

 
30-Jul-13
31  Comments  |  Trackback Url  | 0  Link to this post

Bookmark this post with:        
 

Links to this post

Comments


منتديات  commented on  Saturday, December 07, 2013  8:08 AM 
The No. 1 patient complaint with autologous transplant for myeloma used to be mucositis before the use at Ohio State of oral cryotherapy. Standard ice-chip therapy requires patients to hold one ounce of ice chips in their mouth, then replenishing them when melted, for 30 minutes before and during, and continuously for six hours after melphalan infusion (seven hours total). Prolonged ice-chip therapy is a hardship for patients.


buy essay  commented on  Sunday, September 07, 2014  5:57 AM 
If there is number one company in world for providing essay services then we would be one on front. We are providing services for last one decay and since then we have received numerous attention from people around the globe.


usammdeals  commented on  Friday, October 10, 2014  6:59 AM 
Experiential travel is mostly about valuing any experiences you undoubtedly have about what that you're told it's best to being engaging in by some other individual. We're many different, we most of enjoy different things and some of our travel have to reflect the fact that.


sparxxrx  commented on  Monday, October 20, 2014  4:29 AM 
All of our male enhancement pills are herbal yet effective. Here at SparXXrX® we truly offer the safest, easiest way for you to naturally increase the size of your penis.


the hindi serials  commented on  Wednesday, October 29, 2014  2:45 PM 
Watch Star Plus HD live free star plus is a Hindi-language general entertainment television channel based in India.  The Star plus tv shows based on bringing drama, reality shows, latest twists, favorite episodes on live star plus


psd loft  commented on  Wednesday, November 12, 2014  2:49 AM 
The Star plus tv shows based on bringing drama, reality shows, latest twists, favorite episodes on live star plus


like it  commented on  Saturday, November 15, 2014  1:57 AM 
based on bringing drama, reality shows, latest twists, favorite episodes on live star plus


Green Smart Living  commented on  Sunday, November 16, 2014  8:09 AM 
Resources like the one you mentioned here will be very useful to me! I will post Anine Bing a link to this page on my blog. I am sure my visitors will find that very useful


homepage here  commented on  Saturday, November 22, 2014  1:46 AM 
I am sure my visitors will find that very useful


treatments for vitiligo  commented on  Wednesday, December 03, 2014  9:47 AM 
In the setting of an ongoing randomized controlled trial of myeloma patients undergoing autologous transplant comparing the incidence of severe mucositis in two-hour versus six-hour schedules of crushed ice therapy


seo services  commented on  Thursday, December 04, 2014  6:24 AM 
for the valuabe information and insights you have so provided here.


Free PDF Links  commented on  Sunday, December 07, 2014  5:12 AM 
ack estrogen and progesterone receptors, and by overexpression of the HER2 receptor. F


high efficiency electric water heater  commented on  Monday, December 08, 2014  8:38 AM 
may not mean much to you, but the insertable measurement just might. You’ll be pleased to know that while this SparXXrX® bullet is small it is mighty as well. a


buy real hgh online  commented on  Thursday, December 11, 2014  1:17 AM 
pleased to know that while this SparXXrX® bullet is small it is mighty as well.


easecox  commented on  Friday, December 12, 2014  7:44 AM 
In the setting of an ongoing randomized controlled trial of myeloma patients undergoing autologous transplant comparing the incidence of severe mucositis in two-hour versus six-hour schedules of crushed ice therapy, we are gathering relevant pharmacokinetic data, performing experiments using patients’


  commented on  Sunday, December 14, 2014  5:41 AM 
pleased to know that while this SparXXrX® bullet is small it is mighty as well.


analisis bq maxwell  commented on  Sunday, December 14, 2014  5:42 AM 
pleased to know that while this SparXXrX® bullet is small it is mighty as well.


fibromyalgia pain management  commented on  Monday, December 15, 2014  2:43 AM 
I comprehend everybody got their own particular presumption, regardless? Tune in, your web log is cool.


εργασια θεσσαλονικη  commented on  Monday, December 15, 2014  1:32 PM 
I comprehend everybody got their own particular presumption, regardless? Tune in, your web log is cool.


hella led lights  commented on  Tuesday, December 16, 2014  2:01 AM 
everybody got their own particular presumption, regardless? Tune in, your web log is cool.


emotional support animals  commented on  Tuesday, December 16, 2014  4:39 AM 
particular presumption, regardless? Tune in, your web log is cool.


emotional support animals  commented on  Tuesday, December 16, 2014  4:40 AM 
particular presumption, regardless? Tune in, your web log is cool.


göğüs kanseri  commented on  Tuesday, December 16, 2014  5:57 AM 
articular presumption, regardless? Tune in, your web log is cool.


tmj dental  commented on  Tuesday, December 16, 2014  7:19 AM 
Spinna has made it simple for you by compiling his short list of classic Moog material from the late-60’s. Here are some of the choice highlights from his list courtesy of MTV Hive:


portable copy machine  commented on  Wednesday, December 17, 2014  2:04 AM 
Here are some of the choice highlights from his list courtesy of MTV Hive


summonerswartool.com  commented on  Wednesday, December 17, 2014  7:30 AM 
simple for you by compiling his short list of classic Moog material from the late-60’s.


plastic storage containers with lids  commented on  Thursday, December 18, 2014  12:48 AM 
the perfect solution to streamline the body naturally without any side effects at all. visit


remodel kitchen  commented on  Thursday, December 18, 2014  4:34 AM 
Design is pretty simple and a good user friendly interface.


small forklifts  commented on  Thursday, December 18, 2014  5:55 AM 
DJ Spinna has made it simple for you by compiling his short list of classic Moog material from the late-60’s. Here are some of the choice highlights from his list courtesy of MTV Hive:


Amelia  commented on  Thursday, December 18, 2014  6:36 AM 
made it simple for you by compiling his short list of classic Moog material from the late-60’s.


screen for ipad 2  commented on  Saturday, December 20, 2014  3:10 AM 
They become mini-clones of the larger system. It is a dehumanizing agenda which fits the controlling schemes of those in power. And so many of us buy into it. They become mini-clones of the larger system. It is a dehumanizing agenda which fits the controlling schemes of those in power. And so many of us buy into it.

Name *:
URL:
Email:
Comments:

CAPTCHA Image Validation