A summary of Rituximab-like studies?

[cigana]

I wonder if someone could give us a summary of what has been done in this area, as I am finding it difficult to differentiate between the different studies completed, ongoing and planned!

If someone could just summarise the following, I'd be grateful:

• What studies have been completed.

• What has been published.

• What is ongoing.

• What is finished but not yet published.

• What is planned for the future.

In each could you mention the number of patients, type of treatment and outcome. Thanks!

 

[deleder2k]

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.

2015:

A new phase 2 study will be published in a few weeks or months. 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 rate that looks similar to the previous study published in 2011. Many more in remission 1-2 years after final infusions compared to the last study in 2011. Probably due to prolonged B-cell depletion (6 infusions versus 2).


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 May 2017. Will probably have to wait until late 2017 or early 2018 for publishing.

Three substudies will be performed:

Endothelial function: assessment of Flow-Mediated Dilation and skin microcirculation at baseline and repeated during the time interval 17-21 months.

Cardiopulmonary exercise test for two following days: assessment at baseline and repeated during the time interval 17-21 months.

Gastrointestinal function: assessment at baseline and repeated during the time interval 17-21 months.

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

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.


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.

 

[cigana]

Great, thank you @deleder2k !

 

[Sasha]

@cigana, there's also a UK RCT of rituximab at University College London planned (and pretty much funded) - details haven't been finalised yet because there's some pre-study research going on that will feed into the design.

 

[cigana]

@cigana, there's also a UK RCT of rituximab at University College London planned (and pretty much funded) - details haven't been finalised yet because there's some pre-study research going on that will feed into the design.

Very interesting! Do we know yet what sort of number of patients this will have and whether they want to go for blinded?

EDIT: Some details on this trial here.

 

[Sasha]

Very interesting! Do we know yet what sort of number of patients this will have and whether they want to go for blinded?

I don't know but @Jonathan Edwards is advising on the trial.

 

[Jonathan Edwards]

I don't know but @Jonathan Edwards is advising on the trial.

There is nothing particular to report just at present. Plans will be discussed at the end of the month.

 

[RL_sparky]

@Jonathan Edwards
Any idea when we might see this paper published or hear about these exciting results?
Thanks

"We are also interested in certain molecules present in serum, which change in relation to B cell activity. We are currently in the process of measuring these molecules in patients with CFS/ME and have already got some extremely exciting results which we look forward to publishing as soon as possible. Briefly, it may help us identify why some patients may respond better than others to rituximab."


http://www.ukrituximabtrial.org/Rituximab news-Aug14 02.htm

 

[deleder2k]

Has it anything to do with CD27+ count or memory b-cells?

 

[Jonathan Edwards]

@Jonathan Edwards
Any idea when we might see this paper published or hear about these exciting results?
Thanks

"We are also interested in certain molecules present in serum, which change in relation to B cell activity. We are currently in the process of measuring these molecules in patients with CFS/ME and have already got some extremely exciting results which we look forward to publishing as soon as possible. Briefly, it may help us identify why some patients may respond better than others to rituximab."


http://www.ukrituximabtrial.org/Rituximab news-Aug14 02.htm

I think it would be wrong for me to make comments on the work Dr Cambridge is doing, while still in the middle of things. Unfortunately, things always take longer than it seems they should, and one needs to wait until people are confident they have fully investigated around initial findings.