The 12th Invest in ME Conference, Part 1
OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.
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Cyclophosphamide in ME/CFS Part A:an Open Label Phase-II Study With Six Intravenous Cyclophosphamide

Discussion in 'Rituximab: News and Research' started by deleder2k, May 27, 2015.

  1. deleder2k

    deleder2k Senior Member

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    The trial "CycloME" is now underway in Norway. The official name is:


    Cyclophosphamide in Myalgic Encephalopathy/ Chronic Fatigue Syndrome (ME/CFS). Part A: an Open Label Phase-II Study With Six Intravenous Cyclophosphamide Infusions Four Weeks Apart, and Follow-up for 12 Months

    It seems that the study is due to be finished in November 2016. That means we probably will have results approximately 1 year before the Rituximab phase 3 is published.

    Here is the information posted on clinicaltrials.gov:

     
    Last edited: May 27, 2015
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  2. Valentijn

    Valentijn Activity Level: 3

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    Looks good, aside from the objective outcomes all being secondary measurements, and the primary outcomes being focused completely on fatigue questionnaires.
     
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  3. Scarecrow

    Scarecrow Annie Gsampel

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    One of the secondary measurements is a two day CPET "for patients who can tolerate exercise" (at baseline, 7-9 and 11-12 months).
     
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  4. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Awesome. Really looking forward to see if ritux non-responders, respond to this or not. And also to see how long remissions last compared to ritux!
     
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  5. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    How else would you do it? (just curious)
     
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  6. Kati

    Kati Patient in training

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    They also have an actometer, which took e represents progress.
     
  7. leokitten

    leokitten Senior Member

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    Sorry @deleder2k if I may ask since this is "Part A" what will be the other parts?
     
  8. Bob

    Bob

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    Interesting to note that the Canadian Criteria are being used and at least two years duration of illness:
     
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  9. deleder2k

    deleder2k Senior Member

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    Part B will be conducted if there is a response rate of ≥ 40% in part A. The same drug is used. Completely bedridden patients that cannot leave their home will be included.
     
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  10. Bob

    Bob

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    Yikes, Cyclophosphamide seems to be a heavy-duty chemotherapy drug, with potential for very severe side effects especially at higher doses. It's not for the faint hearted. But I don't know how dose size for autoimmunity compares with dose size for cancer - perhaps lower doses might make a significant difference for the side-effect profile and potential for adverse events.
    http://en.wikipedia.org/wiki/Cyclophosphamide

    I'm not familiar with the drug or its mechanism of action but it is used to treat severe autoimmune conditions including rheumatoid arthritis, and seems to have a mechanism of action via T cells. (Perhaps we've discussed this before? I can't remember):
    http://en.wikipedia.org/wiki/Cyclophosphamide#Mechanism_of_action
     
    Last edited: May 27, 2015
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  11. deleder2k

    deleder2k Senior Member

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    They use 600-700mg/m2. I think that is common for breast cancer (a long with several other medicines at the same time). I heard somewhere that 600-700mg/m2 is safer once in a while than having a low dose often.

    In cancer they can give up to 3-4 g/m2 if I am not mistaken.
     
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  12. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    Yep! Not a walk in the park-drug by any means, but it doesnt seem too bad either with regards to the actual chances of getting serious side effects "Myeloproliferative neoplasms, including acute leukemia, non-Hodgkin lymphoma, and multiple myeloma, occurred in 5 of 119 rheumatoid arthritis patients within the first decade after receiving cyclophosphamide, compared with one case of chronic lymphocytic leukemia in 119 rheumatoid arthritis patients without a history of cyclophosphamide use."

    However - Acute leukemia, e.g, is a very very serious diagnosis indeed.
    In other words - not a drug to take in a heartbeat!
     
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  13. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    cyclo-risk.png

    From the study comments: "Because lymphoma is a cancer arising from lymphocytes, it is not surprising that diseases characterized by immune system dysregulation (including RA, among others) are associated with malignant transformation of lymphocytes. Similarly, T-cell large granular lymphocyte leukemia is a disorder often associated with autoimmune disorders, especially RA, and particularly in patients with Felty syndrome. This malignancy of cytotoxic T cells is characterized by dysregulated apoptosis and may be antigen driven.20 Controversy continues, however, as to how much of the total risk of hematologic malignant neoplasms in RA is related to the disease process itself vs to immunosuppressive medications; recent data suggest both aspects are likely important.13 Immunosuppressive drugs have been linked to the development of both leukemia and lymphomas, and immunodeficiency, whether innate or acquired, is a strong risk factor for certain lymphomas. In many cases, this association relates to the emergence of Epstein-Barr virus–driven malignant proliferations; however, in RA, this does not seem to be the only driving force.13 Impaired immune surveillance can prevent the deletion of abnormal cells, a phenomenon that may have been magnified in our study design, which focused on an older cohort."
     
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  14. Valentijn

    Valentijn Activity Level: 3

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    Have one or more objective measurements as primary outcomes instead of secondary, and move the fatigue questionnaires into secondary outcomes. The current set up allows them to say the treatment is a success if "fatigue" answers improve, even if actual disability stays the same or worsens.
     
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  15. Bob

    Bob

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    Yep, if you're one of the unlucky 5 in 119 who gets lymphoma or leukaemia then it's definitely not a walk in the park. I can't see me wanting to take this drug. But if it were to have a guaranteed and substantial benefit then I should imagine that it would be something that very severely affected patients may potentially consider.
     
    Last edited: May 27, 2015
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  16. Bob

    Bob

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    I agree with you Val, but at least they are including very decent objective measures, and the data will hopefully be published upfront and transparently.
     
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  17. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    I see your point.

    But as far as i can tell that is accounted for with "fatigue" just being one of the 4 symptoms ("Post-exertional malaise", "Need for rest", "daily functioning")

    I see the biggest problem being patients not being completely honest.
     
  18. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    I agree. However, a fair point is that we probably got a fair chance of getting b-cell related cancer in the first place with ME. So if you got the approx same chance of attaining some other cancer, with cyclo, but your healthy.. Well then it kinda makes sense to go for it if all else fails?
     
  19. Bob

    Bob

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    I think the decision to take cyclo would be a very personal choice and would depend on the severity of ME/CFS and on whether cyclo guarantees a substantial and sustained improvement in every patient it is prescribed to. If you were to get no benefit from it, or short-term benefit, but you developed cancer a few years down the line then it's not a good deal.

    I'm not convinced by your assertion that we "probably got a fair chance of getting b-cell related cancer in the first place with ME." We do have an increased risk of developing certain specific cancers, but I'm not sure there is robust data for this, and I'm pretty sure it's not anywhere near as high as 5 in 119 for leukaemia and lymphoma etc over a ten year period? As far as I remember, it's a substantially increased rate, compared to the general population, but the rates are still very low. If it were as high as 10% over a ten year period, then I think we'd know a lot of forum members who had developed cancer over the past few years. (Note that the cancer rates that you've posted are for a ten year period, and not lifetime.)
     
    Last edited: May 27, 2015
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  20. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

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    "CFS was associated with diffuse large B cell lymphoma (OR = 1.34, 95% CI = 1.12-1.61), marginal zone lymphoma (OR = 1.88, 95% CI = 1.38-2.57), and B cell NHL not otherwise specified (OR = 1.51, 95% CI = 1.03-2.23)."

    Source: http://www.prohealth.com/library/showarticle.cfm?libid=17017

    Not too good in statistics, could anyone explain in laymans terms?:)

    Edit: The authors caution that; the study was limited to people aged 66 years and older, so that the findings may not be generalisable to younger (non-elderly) populations. Furthermore, they warn against any direct interpretation or application of these results in a clinical setting; as they say, “We could not estimate the absolute risk of non-Hodgkin lymphoma associated with CFS, but the risk is likely too small to affect the clinical management of patients”.

    Second edit: In other words you are probably right Bob!
     
    Last edited: May 27, 2015

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