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Status of current and past Rituximab studies

deleder2k

Senior Member
Messages
1,129
Some may have seen this before. But I think a quick summary is beneficial for new readers.

Rituximab history

2009


First Rituximab study published: Clinical impact of B-cell depletion with the anti-CD20 antibody rituximab in chronic fatigue syndrome: a preliminary case series

2011:

Phase 2 with double-blinded placebo-controlled study published with 30 patients: Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study

2 infusions of Rituximab two weeks apart. Significant effect from 67% in the Rituximab group and 13% in the placebo-group.

2012:

Study on severely sick patients:

We are also conducting an open-label phase II study (KTS-3-2010) aiming to include only patients with either very severe or severe ME/CFS, using the same treatment regimen with rituximab induction and maintenance as described in the study presented here (KTS-2-2010). Patients with very severe ME/CFS have special needs, and both transporting and accommodating them in a busy oncology ward have proved very difficult. Eight patients have been included, and only four with very severe ME/CFS have been given rituximab maintenance treatment in KTS-3-2010. Although the treatment had a slight beneficial effect on two out of four patients with very severe ME/CFS, none of the four will be characterized as responders.

The study has ended and will not be published.
My understanding is that Rituximab doesn't produce the same effect for those who suffer from severe ME.

Source: The Biggest Chronic Fatigue Syndrome Treatment Trial ...

2015:
28 patients received Rituximab. No placebo-group. 6 infusions on day 0, day 14, after 3 months, 6 months, 9 months and 15 months. Data from a grant application shows a response is similar to the previous study published in 2011. 2/3 responded favorably to the drug. Many more in remission 1-2 years after final infusions compared to the last study in 2011 (61% versus 20%). Probably due to prolonged B-cell depletion (6 infusions versus 2).

Study: B-Lymphocyte Depletion in Myalgic Encephalopathy/ Chronic Fatigue Syndrome. An Open-Label Phase II Study with Rituximab Maintenance Treatment

Clinically significant responses were seen in 18 out of 28 patients (64%) receiving rituximab maintenance treatment. For these 18 patients, the mean response durations within the 156 weeks study period were 105 weeks in 14 major responders, and 69 weeks in four moderate responders. At end of follow-up (36 months), 11 out of 18 responding patients were still in ongoing clinical remission. For major responders, the mean lag time from first rituximab infusion until start of clinical response was 23 weeks (range 8–66). Among the nine patients from the placebo group in the previous randomized study with no significant improvement during 12 months follow-up after saline infusions, six achieved a clinical response before 12 months after rituximab maintenance infusions in the present study. Two patients had an allergic reaction to rituximab and two had an episode of uncomplicated late-onset neutropenia. Eight patients experienced one or more transient symptom flares after rituximab infusions. There was no unexpected toxicity."

Late 2017/early 2018:

A blinded, placebo-controlled multi-center study with 152 patients. First patients received infusions on the 27th of October 2014. Last patient is yet to receive first infusion. Looks like the study is over in July 2017. Will probably have to wait until late 2017 or early 2018 for publishing.



Source and more information: B-lymphocyte Depletion Using Rituximab in Chronic Fatigue Syndrome/ Myalgic Encephalopathy (CFS/ME). A Randomized Phase-III Study. (RituxME)


They are also carrying out a study on cyclophosphamide after a small pilot study showed a major effect in 2/3 subjects. The study has just begun and it will probably be finished before the phase 3 Rituximab study due to the early reponse rate compared to B-cell depletion.


These are the ones to thank:
WDRFSUtW.jpeg

dr. Olav Mella, study coordinator Kari Sørland, and dr. Øystein Fluge (Photo by the Kavli foundation)
 
Last edited:

Bob

Senior Member
Messages
16,455
Location
England (south coast)
They have also carried out an open Rituximab pilot study on patients with severe ME. It is unpublished as of 2015, and will probably not be published. My understanding is that the experience is that Rituximab doesn't produce the same effect for those who suffer from severe ME. Some had an effect, while others were classified as non-responders.
There seems to be a bit of info about this here (note that the outcomes discussed are in relation to very severely affected patients):
http://forums.phoenixrising.me/inde...aintenance-treatment.38477/page-2#post-613781
 

deleder2k

Senior Member
Messages
1,129
Why is the pilot study showing nonresponse in very severely and severely affected ME patients not going to be published? These findings are of major clinical interest.

I don't know. I don't think they completed the study. I guess there is nothing to publish. I think they have mentioned their findings in the latest published paper.

If part A of the cyclophosphamide trial is positive, they will do a study on severely sick patients (completely bedridden).
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
My understanding is that Rituximab doesn't produce the same effect for those who suffer from severe ME.
Why is the pilot study showing nonresponse in very severely and severely affected ME patients not going to be published? These findings are of major clinical interest.

Do we actually know they do not respond? What is implied here is that they don't respond as well as less severe patient responders.

The phase 3 trial may well address this. I hope it does.
 

deleder2k

Senior Member
Messages
1,129
This kind of study is needed on all treatments for ME and CFS. Sadly it often has not happened in the past.

Absolutely. It is very difficult to do though. I think the plan is to infuse cyclo where patients live. They would need a doctor, a nurse, equipment at each patients home. It is very costly and time consuming.
 

deleder2k

Senior Member
Messages
1,129
Do we actually know they do not respond? What is implied here is that they don't respond as well as less severe patient responders.

That is correct. The first impression is that they respond less favorably in general.
 

Martial

Senior Member
Messages
1,409
Location
Ventura, CA
very interesting, is this something currently being offered on the market? Or clinical trials for an unreleased pharmaceutical.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
very interesting, is this something currently being offered on the market? Or clinical trials for an unreleased pharmaceutical.
Rituximab is an established and available treatment for rheumatoid arthritis, lymphoma, and I think other diseases. The phase 3 trial which will give a strong basis to it being an effective treatment is due to be completed in 2017.
 

alex3619

Senior Member
Messages
13,810
Location
Logan, Queensland, Australia
Absolutely. It is very difficult to do though. I think the plan is to infuse cyclo where patients live. They would need a doctor, a nurse, equipment at each patients home. It is very costly and time consuming.
Yes, and ME and CFS have been massively underfunded. The lack of funding has meant these studies have not happened, all too often. Only a very few have done such studies, though the mindset is changing and such studies are now becoming considered as mandatory.
 

msf

Senior Member
Messages
3,650
Wouldn't publishing the severe ME study potentially be just as informative as any of the other studies?
 

Sidereal

Senior Member
Messages
4,856
I don't know. I don't think they completed the study. I guess there is nothing to publish. I think they have mentioned their findings in the latest published paper.

Yes, I posted the excerpt on the other thread. Even though the study wasn't completed, they seem to have treated 4 severe/very severe ME patients with RTX as part of that study. They could publish it as a case series just as they did the original 3 cancer patients with ME. Negative results are just as important as positive results in helping clinicians and patients make informed decisions about treatment.
 

Bob

Senior Member
Messages
16,455
Location
England (south coast)
There seems to be a bit of info about this here (note that the outcomes discussed are in relation to very severely affected patients):
http://forums.phoenixrising.me/inde...aintenance-treatment.38477/page-2#post-613781
Yes, I posted the excerpt on the other thread. Even though the study wasn't completed, they seem to have treated 4 severe/very severe ME patients with RTX as part of that study. They could publish it as a case series just as they did the original 3 cancer patients with ME. Negative results are just as important as positive results in helping clinicians and patients make informed decisions about treatment.
I think it's important to note that the four patients that are discussed in the excerpt, in terms of their response to treatment, were very severe patients only. It doesn't mention how the four severe patients responded. As far as I understand it.
 

deleder2k

Senior Member
Messages
1,129
It has come to my attention that the study on the severely sick with Rituximab has not ended. To my understanding they are in the progress of doing it. I can't edit my first point. I am sorry for the misinformation.
 

greeneagledown

Senior Member
Messages
213
@deleder2k, do you know if they've filled up the phase 3 Rituximab study yet, or are they still recruiting? The clinicaltrials.gov page for the study hasn't been updated since December.
 

deleder2k

Senior Member
Messages
1,129
There has been some delay at the University Hospital of North Norway. From what I've heard they are still not done. I have heard early autumn. They will probably get the last patients going after the summer break is over.