Thrombotic Thrombocytopenic Purpura, Acquired
Conditions
Keywords
daratumumab, thrombotic thrombocytopenic purpura, ADAMTS13
Brief summary
Data about efficacy and safety of daratumumab in iTTP refractory or intolerant to standard immunosuppressive treatments are scarce. Therefore, the investigators aim at collecting evidence on a larger number of patients through a collaborative, international study.
Detailed description
iTTP in an autoimmune disease caused by autoantibodies directed against the metalloproteinase ADAMTS13. Rituximab is the standard immune suppressive treatment suggested from international guidelines. However, 10-15% of patients do not achieve a sustained ADAMTS13 remission with rituximab, and a significant portion of responders eventually need re-treatment after 12 months or less. Other therapeutic options are scarce and based on old immunosuppressive agents or splenectomy, all burdened by relevant toxicity and lack of solid efficacy data. Recently, targeting CD20-negative long-lived plasma cells appears to be a promising strategy in refractory iTTP. The anti-CD38 monoclonal antibody daratumumab has been employed in selected iTTP patients with good results. However, evidence stems only from isolated case reports. The DarTTP study aims to collect evidence on a larger number of patients about the efficacy and safety of daratumumab in iTTP subjects who are refractory or intolerant to previous immunosuppressive treatments. The primary endpoint is the proportion of patients with ADAMTS13 activity levels above 20% of normal at 6 months from the first daratumumab administration.
Interventions
None listed
Sponsors
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Study design
Observational model
CASE_ONLY
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* patients with a confirmed diagnosis of iTTP (i.e., ADAMTS13 activity \<10% with anti-ADAMTS13 antibodies detected); * aged ≥ 18 years; * male and female patients; * treated with daratumumab for iTTP.
Exclusion criteria
* patients unwilling or unable to provide their informed consent; * follow-up \< 6 months after daratumumab administration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of responders to daratumumab | From the first daratumumab administration to 12 weeks after the last dose | Number of patients responding to daratumumab / total number of patients treated with daratumumab (response defined as the achievement of ADAMTS13 activity levels above 20% of normal at any timepoint from the first daratumumab administration to 12 weeks after the last dose, without new additional immunosuppressants) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of daratumumab | From the first daratumumab administration to 24 weeks after | Number of adverse events related to daratumumab, using CTCAE v5.0 |
| Duration of response | From the date of the first documented ADAMTS13 activity >20% after the first dose of daratumumab until the date of ADAMTS13 relapse (i.e., ADAMTS13 activity <20%), assessed up to 3 years. | Median ADAMTS13 relapse-free survival after daratumumab treatment |
Countries
Italy
Contacts
CONTACTJuri A Giannotta, M.D.
Outcome results
None listed