The Leukemia & Lymphoma Society - Fighting Blood Cancers
17 Replies Latest reply: Jun 26, 2012 6:30 PM by Tex RSS

US-ATG-F clinical trial

kimmy1171 Registered Users
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Hi all!

My 38 yr old brother was diagnosed with AML FLT3+ April 11th and I have been trolling these boards ever since.  I feel like I know you all having read your stories and advice and figured it was time to introduce myself, so hello there I'm Kim  I cannot say enough what it has meant to me to visit this board and the knowledge and heartfelt concerned contained herein.  What a blessing you all are to others traveling this path.  Chris has been through induction and achieved 100% remission with the first go round, so of course we're feeling very lucky there!  He has had one round of consolidation and this week we have received word that they have found a donor, so he is scheduled for BMT beginning July 6th at UPenn.  They have offered him the option of participating in the US-ATG-F clinical trial for help with chronic GVHD and I was wondering if anyone has any experience of thoughts on the matter.  I can provide some further detail of his situation if need be.  Chris and his wife are the sort of folk that would prefer to deal with what is happening today and not dwell too much on future plans where I am more of a knowledge is power person, so rightly so he has asked me to look into it for him and offer up any sage counsel I can find, so here I am....Thanks in advance and again its a real pleasure to be making your acquaintance!!

Kim

  • Re: US-ATG-F clinical trial
    Tex Registered Users
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    ATG has come along since my SCT or, at least, it didn't play a roll in mine.  I do think it's pretty new as a GVH treatment.  But, if I remember correctly, that's what they're using it for in transplants.

     

    My only advice with this type of clinical trial is to know who's going to pay the bills if things go south,  Insurance won't usually cover trials that went bad and the trials don't seem to usually provide money for that, either.  Sure, most of the things that could go wrong can usually be treated as a result of the transplant so it's paid by insurance.  But what if it isn't?  That's what kept e out of one trial they wanted to do on me.

     

    Full disclosure, I just read the trial's papers and didn't ask anyone to clarify for me if I read that correctly or not.  Then again, I was about to undergo a life threatening procedure to treat a life threatening disease.  I wasn't in the mood to rely on someone else's interpretation of what would happen as I had enough crap I was having to rely on anyway.

     

    Blessings

    • Re: US-ATG-F clinical trial
      kimmy1171 Registered Users
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      Thanks Tex!  I will definitely pass that info along.  Although he loves his doctors, it's odd how little information he is able to glean when asking point blank questions but in this case when asked about what she thought of his participating, his doctor said. "Ech".  That doesn't sound particularly encouraging. 

      • Re: US-ATG-F clinical trial
        mamawarrior Registered Users
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        I thought ATG was commonly used during  pretransplant conditioning (son received it  in 2006) however i recall some cases of steroid refractory GVHD where folks have had to have ATG post transplant also.

         

        Curious as to what the difference is in this clinical trial (is it given before, after etc) and what the F stands for? Most folks end up on immunosuppressants post transplant, does this clinical trial address that and does it alter the need for immunosuppressants??

         

        If you have a link to the clinical trial, please post. Would try to google it but my google is under the weather.

         

        By the way, my son has been on 3 clinical trials, maybe it is my insurance but we had no problems with insurance covering it. What phase clinical trial is this?? That could be a big factor in determining to proceed or not. 

        • Re: US-ATG-F clinical trial
          Tex Registered Users
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          So, Tad and MW, am I completely off about ATG being used to somehow prevent or reduce GVH?  I could swear I've read about that here before.

           

          But, have I mentioned I have chemo brain?

          • Re: US-ATG-F clinical trial
            tadly Registered Users
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            Tex -  I'm still trying to get a handle on what ATG is claimed to be doing and terminology/dynamics of graft and host issues.

             

            The NMDP site lists ATG among the standard prophylactic, immunosuppressive medications to prevent acute GvHD.

             

            The studies for my protocol are harder for me to follow when they  get into comparing to other approaches/studies and bout ATG's effects on T-cells and NK cells, and continued effects on Graft v Leukemia.

          • Re: US-ATG-F clinical trial
            mamawarrior Registered Users
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            Tex, when steven received ATG i remember being told that it was to aid in engraftment, to help the baby u cord stem cells "stick" but i dont recall any discussion about ATG and gvh. It seemed like it was common procedure for unrelated donors but i dont know if back in 2006, much was known about the properties it has against gvhd or if they just explained it to me as aiding in engraftment and i just didnt catch the gvhd/immunosuppressant connection. I never did understand why some folks got 'horse' and why some got 'rabbit' but i do remember a few that either relapsed or failed to engraft given rabbit the 2nd time.

             

            It does seem like it has been mentioned here as a common pretransplant condtioning agent but as a big gun to turn to post transplant for serious steroid refractory gvhd when all else fails.

             

            Tadly, i think it is hard to compare the various approaches because they all are so unique in type of transplant, pretransplant conditioning, immunosuppressants,  dosages,  along with you, your type of blood cancer, your age, health etc etc. Steven was a double u cord stem cell transplant at age 20, recieved ATG for 2 days a couple of days prior to transplant along with other drugs (Melphalan). His t cells and nk cells at 100 days post transplant were in the toilet. His cd4 count was 38 but he also received TBI pre transplant which along with u cord cells may have been a big factor.

             

            Is your protocol supposed to be more ablative, if that is the word, to the t cells and nk cells than other similar approaches in like subjects?? If so, is there any mention regarding infections??

            • Re: US-ATG-F clinical trial
              CherylLynn Registered Users
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              I had 4 days of ATG as part of my pre-transplant regimen - I had the rabbit version and they told me it was given to aid in engraftment but also to help ensure that I did not get acute gvhd - even though my cells were processed to ensure that I received minimal to no gvhd there was always a chance that the processing could have "failed" - I had a Haplo trial transplant in Jan 2011 with cells from my 1/2 matched sister

               

              Cheryl

              • Re: US-ATG-F clinical trial
                Tex Registered Users
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                Thanks, folks.  I'm glad to know I wasn't off base with the GVH thoughts.  With my chemo brain and the simple passage of time, I do get some things mixed up and it's always good to know if I've been on base or off. 

            • Re: US-ATG-F clinical trial
              tadly Registered Users
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              mamawarrior,

               

              You got me trying to understand the last published update of the protocol (2009).  I haven't noticed mentions of the protocol's effect on infections.

               

              The protocol appears to be selective to the host's T-cells and natural killer T-cells rather than more (or less) "ablative" to use your term.  My guess at interpreting it is that the protocol does not wipe out all the Host's T-cells, it leaves a greater amount of the Host's NKT-cells which specifically stimulate or alter the Donor's T-cells in a way that avoids the acute GvHD.  

               

              However, I don't know what's attributed to ATG.  The radiation is this protocol, the TLI, is targeting the "lymphoid" or lymph nodes and certain closely related organs.  So the radiation does not affect the bone marrow directly, and it avoids other organs.   It differs from Total Body Irradiation which is the prevailing radiation technique.

  • Re: US-ATG-F clinical trial
    tadly Registered Users
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    ATG is a key part of my preparatory regimen for a BMT which I'll be starting in just 11 days.   A TLI-ATG protocol has become a standard at my hospital, but a standard for non-myeloblative transplants (a reduced intensity regimen).  The TLI-ATG trials had reported a comparatively low rate of acute GvHD.

     

    This BMT board has a number of posts on ATG.

     

    I'm 64 yrs old and also with AML FLT3+.  I've been in complete remission after my induction (a clinical trial) in Feb., and subsequent 2 rounds of consolidation.  I'm doing a non-myeloblative transplant treatment because at my age a full myeloblative would be too risky.  TLI is a focused radiation treatment (Total Lymphoid Irradiation). 

      

    With my doctor the degree of donor match is a factor affecting my likelihood of having chronic GvHD, with my treatment that includes ATG. I have a 9 or 10  donor match.

  • Re: US-ATG-F clinical trial
    nana Registered Users
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    In my experience ATG is used for both.  My son has failed engraftment and severe liver/gi  gvhd.  He just finished conditionning for transplant #2 and it included 5 days of ATG--doctors explained it would have a dual benefit  1. aiding marrow to be a hospitable place for new stem cells   2. killing off T cells causing GVHD he is fighting now and hoping it sticks around to ease possible GVHD with new transplant.  My son just turned 15, so dealing with pediatrics, but doctors are saying that since GVHD is steroid refractory and first transplant was a failure that ATG is our only hope because, if tolerated, you get double bang for your buck.

     

    As for clinical trials, for us in pediatrics, everything we have done since starting this journey in 2008 has been part of a study.  I feel if my son's struggles can help provide clues to help future children then we are in.  Treatment is still tailored to him and we can pull out whenever we want.

    • Re: US-ATG-F clinical trial
      mamawarrior Registered Users
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      Nana, i am so sorry to hear of your sons failure to engraft. I just want you to know we have had others on this forum that have failed also and had successful 2nd transplants. We heard not to long ago from the husband of a woman that failed to engraft a couple of years ago and is doing very well. I wish you all the best and will certainly hold your son in my prayers.

      • Re: US-ATG-F clinical trial
        nana Registered Users
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        Mamawarrior,

         

        I don't want to hijack the thread but thank you.  Right now its not the 2nd transplant so much as the secondary effects of no immune system since March and GVHD.

        Today is scheduled to be Day 0, but still waiting to hear ok from Drs as we are walking a tightrope here. 

  • Re: US-ATG-F clinical trial
    kimmy1171 Registered Users
    Currently Being Moderated

    Hi all,

    Internet down all day, so I am just reading your responses now.  Thanks much for the input!  His doctor did not mention any benefit for engraftment, just for a potential reduction in chronic gvhd, so it seems this info is a bit at odds with your experiences.  They advised that it would suppress his T cell production post BMT so he might be slower in recovering and obviously that is a concern.   They said the regimen is that he would be given ATG for several days prior to the actual BMT (that is, if he gets the drug at all...it's a 50/50 blind study).  Looking online, it looks like the trial is in phase 3 and the early numbers look OK for a reduction in gvhd.  From what you all have said, am I correct in assuming that ATG is used for tougher cases where there has been a prior relapse and/or issues with gvhd?  I don't know what to tell him and I don't feel like I have enough time to get all the ducks in a row to really understand the situation as he has to let them this Thursday.  For example, is the only drawback the decrease in T cell production?  From what I have been reading, it seems as if the donor match might be something that he should really have an answer on as regards the potential for gvhd and thus his decision.  When he asked all they said was that it was a very good match.

    Thanks again for your help!

    • Re: US-ATG-F clinical trial
      mamawarrior Registered Users
      Currently Being Moderated

      From what you all have said, am I correct in assuming that ATG is used for tougher cases where there has been a prior relapse and/or issues with gvhd?

       

      I think it is fair to say that yes it is used for 'tougher cases' but from what i understand and have read, it is pretty much standard protocal prior to transplant. It may be that when a person fails to engraft or has a steroid refractory gvhd that ATG is used in a different way (highter dosage etc.)

       

      As far as a decrease in T cell production and potential slower recovery, that is a concern but a vague statement. How slow of a recovery? Does it delay engraftment by a day or two, or weeks? I guess you would have to see that data on that to evaluate.

       

      Its a difficult decision. While gvhd seems to be most often controllable, there are the cases of serious life threatening GVH. But the treatment for gvhd is often steroids which in itself has long term effects plus the fact that it is suppresses the immune system  leaves the patient susceptible to infection as well as concern for reactivation of dormant viruses.

       

      By any chance is this transplant a peripheral stem cell transplant or bonemarrow transplant. (Peripheral if i remember correctly, in general has more gvhd) Also the timing for engraftment is different but i dont recall if peripheral is slower to engraft, hopefully someone can clarify that. (Son had U cord stem cells) Those may be factors you want to look at too.

    • Re: US-ATG-F clinical trial
      nana Registered Users
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      At our hospital, in Canada and pediatric, ATG is used in non-myleoblative conditionning.  So when someone presents that cannot handle TBI(radiation) and tough chemo regimes, when transplant is for non-cancer illness, or in "tough cases" like my son.  His 1st transplant was in March so he has already been through a myleoblative conditionning and he has tried campath (related ATG, as it is a monoclonal antibody) to control GVHD once it was found to be steroid refractory.

      I don't know about delaying engraftment but the fact that ATG kills/suppresses Tcells is what allows it to work against GVHD.  My son also had an allergic reaction to his first dose(airways closing), it was controlled with benedryl and every dose after was fine, but that would be a potential drawback. 

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