Daratumumab in Immune-mediated Thrombotic Thrombocytopenic Purpura (DarTTP)

DarTTP: an Observational, International, Multicentric Study on Daratumumab in Immune-mediated Thrombotic Thrombocytopenic Purpura (iTTP)

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.

Study Overview

• Status: Recruiting
• Conditions: Thrombotic Thrombocytopenic Purpura, Acquired

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.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Juri A Giannotta, M.D.; Phone Number: +390255035273; Email: juri.giannotta@policlinico.mi.it

Study Locations

• Italy
  • Milan, Italy
    • Recruiting
    • Angelo Bianchi Bonomi Hemophilia and Thrombosis Center
    • Contact: Juri A Giannotta, M.D.; Phone Number: +390255035273; Email: juri.giannotta@policlinico.mi.it
    • Principal Investigator: Juri A Giannotta, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study includes adult iTTP patients who were treated with daratumumab in the acute phase of disease (i.e., with plasma exchanges and/or caplacizumab ongoing) or during remission (i.e., due to ADAMTS13 relapse or ADAMTS13 activity plasma levels persistently <20%) from January 2010 to 6 months before the time of data collection. It includes iTTP patients receiving daratumumab either for refractory disease or in ADAMTS13 remission but intolerant to other immune suppressive agents.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Adult patients with iTTP; Patients with a confirmed diagnosis of iTTP, aged ≥ 18 years, treated with daratumumab for iTTP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of responders to daratumumab	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)	From the first daratumumab administration to 12 weeks after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of daratumumab	Number of adverse events related to daratumumab, using CTCAE v5.0	From the first daratumumab administration to 24 weeks after
Duration of response	Median ADAMTS13 relapse-free survival after daratumumab treatment	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.

Collaborators and Investigators

• Sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: January 19, 2026
• First Submitted That Met QC Criteria: March 30, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: ADAMTS13; daratumumab; thrombotic thrombocytopenic purpura
• Additional Relevant MeSH Terms: Cytopenia; Pathologic Processes; Hemorrhage; Skin Manifestations; Hematologic Diseases; Blood Coagulation Disorders; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Thrombocytopenia; Thrombophilia; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hemic and Lymphatic Diseases; Purpura, Thrombotic Thrombocytopenic; Thrombotic thrombocytopenic purpura, acquired
• Other Study ID Numbers: 6442

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No