New pilot study in the loop from the researchers at Haukeland

[Adele]

Google translation from norwegian

Cyclophosphamide for myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS)

Scientific title:
Cyclophosphamide BY myalgic encephalomyelitis / chronic fatigue syndrome (ME / CFS)

Part A, for up to 30 patients with ME / CFS: An open phase II trial with 6 cyclophosphamide infusions 4 weeks apart

Part B, for up to 20 patients with severe and very severe ME / CFS: An exploratory study with up to 6 cyclophosphamide infusions 4 weeks apart, in collaboration with local health services

project description:
The purpose of this study is to investigate whether cyclophosphamide infusions given every four weeks is associated with clinically significant responses and acceptable side effects in ME / CFS patients, and whether such treatment if necessary. Workable in patients with severe and very severe ME / CFS. The primary endpoint will be based on patients' self-report of symptom development. The application relates Part A: An open-label phase II study for up to 30 patients with ME / CFS (not mild) with six infusions cyclophosphamide every fourth week, 12 months follow-up. If at least 40% response rate in Part A, then part B: A descriptive study with up to 20 patients with severe and very severe ME / CFS, with the same treatment, but where monitoring and intervention carried out in collaboration with healthcare close patient home.
(Project Manager project)

Ref. No .: 2014/1672 EudraCT Number: 2014-004029-41 Project Start: 01.01.2015 Project End: 30/06/2017

Treatment Status: Approved
Research Status: Ongoing
Project: Øystein Fluge
Research Responsible (s): Haukeland University Hospital
Initiator: Contributions Research
financing:
Study researcher initiated. There is no external sponsor of the clinical trial. Research Group for ME / CFS Oncology Haukeland University Hospital has support from the Kavli Foundation, essential for research purposes to better understand the pathogenetic mechanisms of ME / CFS. Kavli Fund has granted a 50% nurse position for 12 months., To help with the study. This is thought transferred to clinical research Post by HUS which will then be responsible for implementation and interventions (study Part A) in collaboration with the study management at Oncology, HUS.

Drug costs are very low (<200 NOK per infusion), ie 1200 NOK per patient for the entire treatment, and will be covered over the research group for ME / CFS Oncology their budget. It is drawn own drug insurance for study. There is no financial compensation for study participants.

 

[lansbergen]

http://en.wikipedia.org/wiki/Cyclophosphamide

 

[melihtas]

Wow it is really cheap, almost free of charge. The biggest dose (1000 mg) is $10 US here in Turkey and I can buy it without a doctor prescription. Now, the question is should I.

There is also a tablet form. 50 mg 50 tablets $8 US.

Sounds a bit scary.
"Cyclophosphamide has severe and life-threatening adverse effects, including acute myeloid leukemia, bladder cancer, hemorrhagic cystitis, and permanent infertility, especially at higher doses. For autoimmune diseases, doctors often substitute less-toxic methotrexate or azathioprine after an acute crisis."

 

[Snow Leopard]

Did anyone guess cyclophosphamide? Because I didn't!


If this drug works, then, we're going to have to ask some much deeper questions about the biochemistry of ME/CFS...

 

[Adele]

I didn't guess anything, because I don't have a clue about different drugs. But if someone who does would care to explain how this works, and maybe also compared to how Rituximab works, that would be very interesting and appreciated

 

[Scarecrow]

Did anyone guess cyclophosphamide? Because I didn't!


If this drug works, then, we're going to have to ask some much deeper questions about the biochemistry of ME/CFS...

Nope!

Mode of action is related to T cells. Can anyone comment?

 

[Snow Leopard]

Abstract:
Cyclophosphamide (CTX), a commonly used chemotherapeutic agent can enhance immune responses. The ability of CTX to promote the proliferation of effector T cells and abrogate the function of regulatory T cells (Tregs) has been described. In this study, we examined the effects of CTX treatment on dendritic cell (DC) subsets and the subsequent outcome on the effector and suppressive arms of adaptive immunity. In secondary lymphoid tissues, tissue-derived migratory DCs (migratory DCs), lymphoid tissue–resident DCs (resident DCs), and plasmacytoid DCs (pDCs) are well described. CTX has profound and selective cytotoxic effects on CD8+ resident DCs, but not skin-derived migratory DCs or pDCs in lymph nodes (LNs) and spleen, causing an imbalance among these DC subsets. CTX treatment increases the potency of DCs in antigen presentation and cytokine secretion, and partially inhibits the suppressor activity of Tregs. Adoptive transfer of CD8+ DCs can reconstitute this population in regional draining LNs and abrogate the immune-enhancing effects of CTX in vivo. These findings demonstrate that CTX may improve immune responses by preferentially depleting CD8+ lymphoid-resident DCs, which leads to diminished Treg suppression and enhanced effector T-cell function in vivo.

From:
http://www.bloodjournal.org/content/115/22/4384.long?sso-checked=true

"abrogate" means: "put an end to".

In general, Cyclophosphamide has been shown to reduce circulating leukocytes, bone marrow leukocytes erythrocytes and platelets. Also, it has been show to inhibit B-cell receptor regeneration.

 

[Sidereal]

I wouldn't touch it with a ten foot pole.

 

[lansbergen]

At higher doses, it is associated with increased cytotoxicity and immunosuppression, while at low, continuous doses, it shows immunostimulatory and antiangiogenic properties.

 

[deleder2k]

Wow! Thank you so much @Adele! This is very interesting.

@Sidereal, why not? Maybe it can give you your life back. What if this drug can cure us?

 

[Sidereal]

Wow! Thank you so much @Adele! This is very interesting.

@Sidereal, why not? Maybe it can give you your life back. What if this drug can cure us?

Too risky for my taste.

 

[Adele]

I wonder what dosages they will use in the study. From what I have been reading, the potential side effects are more serious for higher doses. And also - it says that the project doesn't end until 30.06.17. I wonder why, as the infusions will only go on for 24 weeks, which is more like 30.06.15.

 

[alex3619]

Too risky for my taste.

That is why we have phase 1-3 clinical trials. By the end we will have a better understanding of the risk profile.

 

[alex3619]

From Wikipedia:

As a prodrug, it is converted by liver cytochrome P450 (CYP) enzymes to form the metabolite 4-hydroxy cyclophosphamide that has chemotherapeutic activity.

If this is accurate and you have a snp analysis of these genes it might help tell you if you can tolerate this. Over or underperforming P450 might lead to problems.

 

[deleder2k]

Too risky for my taste.

Do you know much about it? How much they use? It is used for several diseases including rheumatoid arthritis.

 

[Sidereal]

Do you know much about it? How much they use? It is used for several diseases including rheumatoid arthritis.

I don't know how much is used. I read a bit about it years ago when I was diagnosed with a connective tissue disease and it seemed quite serious with respect to possible side effects.

 

[deleder2k]

It is a drug that requires serious follow up from a oncologist/rheumatologist (?). It is used on a daily basis in cancer and AI diseases. If it can get me my life back again, I am willing to to go with it the effect have been demonstrated in a phase 3 double blinded RCT.

 

[NK17]

Thanks @Adele for posting the link.

From this study it's evident that Dr. Fluge and Dr. Mella are investigating a range of treatments' options for us.
Like for many other serious diseases there are choices to be made and first, second and third line desease modifying therapies.

From a first superficial reading on Cyclophosphamide on the web it does seem to carry some heavy and scary potential side effects (at higher dosage), I understand where @Sidereal's comment is coming from.

I'm tagging @Jonathan Edwards to hear what he has to say about.

 

[deleder2k]

Fascinating that 6 infusions of cyclo are around 105 quid, or roughly $160.

In Norway 1 gram of Roche's Rituximab costs £1,300. In the Rituximab study I think they approximately use up to 1g for the two first infusions, then 500mg for maintenance. With 6 infusions that is around £5,200.

In pure drug costs, Rituximab is 50 times more expensive than good old cyclo!

 

[Kati]

I can't read the translation but Cyclophosphamide is an interesting choice.

From my cancer nursing perspective, here is what I know about 'Cyclo.
This is a 'real' chemo drug. It means that it is kills the cells in the body that reproduce fast, including the blood cells, white and red blood cells, and hair cells (it makes you lose your hair), although it is dose dependant. Small dose means less side effects.

Losing the protection of the white blood cells results in neutropenia for a period of time, making the patient prone to potentially dangerous infections. Of course it would be dose dependant, and the dosage here is not specified. I would love to hear Dr Fluge and Mella's feedback, and also Dr @Jonathan Edwards's thoughts, since I believe Cyclo is also being used in rheumatology.

There is also significant bladder toxicity to be considered but this is also dose dependant-high dose means much increased risks. Usually for small doses, patient is hydrated and instructed to drink plenty and to empty the bladder often on chemo day so the Cyclo is not allowed to sit in the bladder for very long.

Certainly this is not a drug to be considered outside clinical trials and competent physicians This is not something you can just try at home.