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Cyclophosphamide in ME/CFS Part A:an Open Label Phase-II Study With Six Intravenous Cyclophosphamide

BurnA

Senior Member
Messages
2,087
Waiting for results and for the next steps, (and hoping the next step gets funded too) is what gets to me. Patience is what's needed here, but at the same time, in my opiniont here should ve clinical trials happening on all continents, not just Norway.

I agree. At least we know that two very important trials are underway and we will have some answers in the next two years.
I would love to see more trials too but maybe there won't be much enthusiasm until the results from Norway are available.
 

BurnA

Senior Member
Messages
2,087
Does anyone know more about the first results from this study and if they will start part B?
Sorry, i'm not so patient :D. I thought they would know by now if the drug works
If the results from CycloME part A are negative, or indicate response in a smaller segment of the participants, part B will not be implemented. An interim analysis of the results from part A will be performed during the first quarter of 2016, and a decision on the possible implementation of part B will be made.


I guess we will know soon
 

BurnA

Senior Member
Messages
2,087
Mella has hinted at a couple occasions that the results so far are good. I expect a part B, and also a later rtx-cyclo trial.

I wondered why they didn't already plan a rtx-cyclo trial. It's probably worth while to wait and see the individual response first before combining.
I read this is one of their letter in plosone :

We admit the strong and repeated responses to new Rituximab infusion seen in our three pilot patients may have influenced us. We have later treated another lymphoma patient with preexisting CFS/ME who also experienced a clear response on all CFS/ME symptoms from four months after start of treatment (8 cytotoxic chemotherapy courses (CHOP) with addition of Rituximab), and she still has response of CFS/ME symptoms 2 ½ years later. Other physicians treating patients having both CFS/ME and lymphoma elsewhere in the world have informed us of similar responses to Rituximab.
 

Kati

Patient in training
Messages
5,497
I wondered why they didn't already plan a rtx-cyclo trial. It's probably worth while to wait and see the individual response first before combining.
I read this is one of their letter in plosone :

It's because the toxicity increases with combination agents. Also if you try 2 agents, you wouldn't be able to tell which agent is contributing the most in improvements.

The down side of separate trials with single agent is that it takes time to yield results. Especially with Rituxan when there is delayed response, where each patients is enrolled for 18 months or so.
 

BurnA

Senior Member
Messages
2,087
It's because the toxicity increases with combination agents. Also if you try 2 agents, you wouldn't be able to tell which agent is contributing the most in improvements.

The down side of separate trials with single agent is that it takes time to yield results. Especially with Rituxan when there is delayed response, where each patients is enrolled for 18 months or so.
Yes that makes sense Kati!
Makes me think that they will wait for both current trials to finish before evaluating if a combination therapy may be worthwhile or not.
It will be very interesting to see if the different drugs produce different responses or not.
 

Gingergrrl

Senior Member
Messages
16,171
Sorry, I have not read this whole thread and have no idea if this question/topic was asked or covered. I was wondering if the people who were responders to Ritux or Cyclo were tested for any auto-antibodies or paraneoplastic antibodies prior to the testing? Has this ever been done? Thank you for any info to anyone who might know!
 

funkyqueen

Senior Member
Messages
123
Location
South of France
BurnA wrote : (impossible ATM for me to quote correctly, do not know why)

" I read this is one of their letter in plosone :[/QUOTE]

(From Fluge) :" We admit the strong and repeated responses to new Rituximab infusion seen in our three pilot patients may have influenced us. We have later treated another lymphoma patient with preexisting CFS/ME who also experienced a clear response on all CFS/ME symptoms from four months after start of treatment (8 cytotoxic chemotherapy courses (CHOP) with addition of Rituximab), and she still has response of CFS/ME symptoms 2 ½ years later. Other physicians treating patients having both CFS/ME and lymphoma elsewhere in the world have informed us of similar responses to Rituximab. "

Thanks @BurnA , thanks to you, i just read the entire commentary on plosone :thumbsup:
 

NL93

Senior Member
Messages
155
Location
The Netherlands
Sorry, I have not read this whole thread and have no idea if this question/topic was asked or covered. I was wondering if the people who were responders to Ritux or Cyclo were tested for any auto-antibodies or paraneoplastic antibodies prior to the testing? Has this ever been done? Thank you for any info to anyone who might know!

http://www.ncbi.nlm.nih.gov/pubmed/26399744
 

Gingergrrl

Senior Member
Messages
16,171

@NL93 Thank you for posting that link and I do remember reading it a long time ago. The link pertains to the muscarinic antibodies (which are very important and relevant for me) but I was curious also if anyone has been tested for Paraneoplastic auto-antibodies (like the PAVAL test at Mayo Clinic) prior to trying Rituximab or Cyclo? My guess is that the answer is no, but still figured I'd ask!
 

BurnA

Senior Member
Messages
2,087
Update

If the results from CycloME part A are negative, or indicate response in a smaller segment of the participants, part B will not be implemented. So far, we do not have sufficient data to decide on the possible implementation of part B. An investigator meeting planned in September 2016 will look at preliminary data for effect and toxicity in CycloME part A, and assess the feasibility of part B.

Status, CycloME part A
All 40 participants have been included in the study and have commenced treatment. The last participant will complete treatment in June, and the study will be completed in January 2017. Unfortunately, we are unable to accept further applications for inclusion in the study.
The results from the CycloME trial, part A will be published in 2017.
 
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Justin30

Senior Member
Messages
1,065
For those considering such a trial, I will mention that the therapeutic effects of CTX in cancer treatment are now thought to be related in part to the induction of intestinal permeability and the attendant translocation of certain microbial organisms. This brings about a robust adaptive immune response that can be abrogated by antibiotic administration. You can read about the specific cellular responses here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4048947/#SD1

Without getting too much into the biochemical similarities between CA and ME/CFS and the transferability of this research, I would suggest these findings certainly might say something about the pathophysiology of ME/CFS. Translocation of bacteria into the mononuclear phagocyte system is also one of the most promising developments in cancer immunotherapy. Fairly recently it was reported that administering tetanus vaccinations could triple the survival advantage in glioblastoma. They found that a simple tetanus vaccine could stimulate the migration of dendritic cells to these extraintestinal tissues.

I can't say I'm enthralled with the idea of this approach after recently witnessing the effects of this medication, but I can relate with the sentiment. In addition to the problems described above, I think the associated incidence of neutropenia is likely to require more than a handful of participants to treat secondary infections with antimicrobials, which according to the study linked above, may negate the desired cellular response.

I studied the metabolic capacities of the organisms believed to be playing a part in immunomodulation in this study some time ago, and I am interested by the finding that describes an extraintestinal proliferation of L. Johnsonii. This is a fairly unusual Firmicutes organism which is part of the lactic acidophilus group. I seem to recall that it is particularly sensitive to O2. It is effective in counterbalancing pathogenic lactic acid bacteria, i.e. reducing strep/enterococcus overgrowth. Honestly, I don't fully appreciate the significance of the accumulation of this particular organism, but it is a very unusual LAB in that lacks encoding for amino acid synthesis and purine metabolism and it acquires these resources from the environment; some of these resources are all but certainly obtained from the host since it is incapable of de novo synthesis.

I guess the take-away is don't take ABX if you choose to pursue this therapy Also, I would wonder if taurine/glycine might enhance the efficacy of this treatment because I know that this organism correlated to the therapeutic benefits is highly resistant to bile and the provision of bile acid precursors has been shown to enhance to effects of CTX, in vitro, at least.

Is CTX Cychlophosophamide? Can you explain how they want to manipulate the GUT Microbiome?

Sorry wrote to much today but am quite interested.

Thanks
 

msf

Senior Member
Messages
3,650
Wow, I just saw the comments about a potential Cyclo-Ritux trial...any volunteers? It would only make sense for those for whom Ritux did not work, in my view. And even then, it seems to me that it would be rather a drastic option.
 

Marky90

Science breeds knowledge, opinion breeds ignorance
Messages
1,253
Wow, I just saw the comments about a potential Cyclo-Ritux trial...any volunteers? It would only make sense for those for whom Ritux did not work, in my view. And even then, it seems to me that it would be rather a drastic option.

It would also make sense for those with moderate responses. Other immune cells (e.g. precursor cells) could possibly be involved in the pathogenesis. Rtx + cyclo is drastic, but so is ME..
 

deleder2k

Senior Member
Messages
1,129
Wow, I just saw the comments about a potential Cyclo-Ritux trial...any volunteers? It would only make sense for those for whom Ritux did not work, in my view. And even then, it seems to me that it would be rather a drastic option.

Where did you read about that?
 

BurnA

Senior Member
Messages
2,087
Do we know if part A was positive and they will proceed with part B?

@deleder2k , @Marky90 , anyone?
From the website link...
If the results from CycloME part A are negative, or indicate response in a smaller segment of the participants, part B will not be implemented. So far, we do not have sufficient data to decide on the possible implementation of part B. An investigator meeting planned in September 2016 will look at preliminary data for effect and toxicity in CycloME part A, and assess the feasibility of part B.