Elective rituximab in TTP

• Register: EUCTR
• Last refreshed on: 11 June 2018
• Main ID: EUCTR2017-001117-86-GB
• Date of registration: 18/05/2018
• Prospective Registration: No
• Primary sponsor: University College London
• Public title: Elective rituximab in TTP
• Scientific title: A phase IV, prospective, randomised single-blind UK multicentre non-inferiority trial of low-dose versus standard dose rituximab for prevention of relapses in acquired TTP - Elective rituximab in TTP
• Date of first enrolment: 25/07/2017
• Target sample size: 52
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-001117-86
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: yes; Double blind: no; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Low dose rituximab; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

United Kingdom

Contacts

• Name: Sponsor Regulatory Advisor
• Affiliation: University College London Joint

• Name: Sponsor Regulatory Advisor
• Affiliation: University College London Joint

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female, age>18
2. Antibody-mediated TTP with at least one previous acute TTP episode
3. ADAMTS13 activity dropping to =15% documented on 2 separate occasions on different days, , with platelets>150 and no evidence of microangiopathic haemolytic anaemia and LDH <1.5 x upper limit normal
4. Females of childbearing potential and males agree to use an effective method of contraception from the time consent is signed for 12 months after treatment completion. Effective methods of contraception acceptable for this trial are oral, implanted or injected hormonal methods of contraception, IUD or IUS, and barrier methods of contraception
5. Females of childbearing potential have a negative pregnancy test within 7 days prior to being randomised. Participants are considered not of child bearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal
6. Willing and able to provide written informed consent.
7. Willing and able to comply with the trial protocol

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 7

Exclusion criteria:
1. Females who are pregnant, planning pregnancy or breastfeeding
2. Concurrent and/or recent involvement in other research that is likely to interfere with the intervention within 3 months of study enrolment
3. Known allergies to rituximab
4. Patients currently undergoing plasma infusion/exchange
5. Patients on therapy with other immunosuppressive medication (except steroids)
6. Patients with a current acute severe infection or a history of recurring or chronic infections or underlying conditions which may further predispose patient to serious infection.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Acquired thrombotic thrombocytopenic purpura

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Trade Name: Mabthera
Product Name: Mabthera
Pharmaceutical Form: Concentrate for solution for infusion

Primary Outcome(s)

Main Objective: We know that a fall in ADAMTS13 activity in remission can be a sign of upcoming TTP relapse. We plan to see if low dose rituximab is as effective as the standard dose in preventing TTP relapse by looking at the length of time until patients need to be treated again with ritiuximab or other immunosuppression

Primary end point(s): The primary outcome will be time to re-treatment with rituximab/other immunosuppression measured in days from day of first rituximab infusion (D1)until D1 of any subsequent course of elective rituximab, or introduction of other immunosuppression initiated with the aim of preventing clinical relapse of TTP.

This will be analysed as a time-to-event variable.

Secondary Objective: We will also look to see if low-dose rituximab is as effective as standard dose rituximab in:
• the time it takes for ADAMTS13 activity to normalise after rituximab
• how long ADAMTS13 stays normal after rituximab
• subsequent relapse rates of patients with a clinical TTP episode
• subsequent re-treatment rates of patients using rituximab or other immunosuppression

and also whether there is a difference in side effects between the 2 doses, either related to the infusion itself or other rituximab-related adverse effects.

Secondary Outcome(s)

Secondary end point(s): Time to normalisation of ADAMTS13 activity–number of days from D1 of first rituximab infusion until ADAMTS13 activity returns to normal range; this is a time-to-event outcome.

Duration of ADAMTS13 response – number of days from normalisation of ADAMTS13 activity to ADAMTS13 activity dropping outside of remains in normal range; this is a time-to-event outcome.

Subsequent relapse rate with clinical TTP episode (%) – the proportion of patients who experience a clinical relapse of TTP during trial follow-up compared to patients who do not; this is a binary outcome.

Subsequent re-treatment rate with rituximab/other immunosuppression (%) – the proportion of patients who are retreated with rituximab or other immunosuppression, for the prevention of clinical relapse of TTP, during trial follow-up compared to patients who are not; this is a binary outcome.

Time to B cell depletion – number of days from D1 to CD19 count <0.005x109/L0.5% ; this is a time-to-event outcome .

Time to B cell return – number of days from D1 to CD19 count returning to normal range; this is a time-to-event outcome.

Infusion-related adverse effects

Delayed rituximab-related adverse effects eg serum sickness, abnormal LFTs, cytopenias, infections- not occurring during rituximab infusion

Secondary ID(s)

16/0340

Source(s) of Monetary Support

Answering TTP Foundation