The DART Study- Daratumumab Treatment in ITP
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04703621|
Recruitment Status : Recruiting
First Posted : January 11, 2021
Last Update Posted : April 13, 2021
|Condition or disease||Intervention/treatment||Phase|
|ITP||Drug: Daratumumab Injection||Phase 2|
Many patients with chronic ITP require repeated or continuous medications to maintain a safe platelet count.
B-cell depletion with rituximab in ITP induces the differentiation of short-lived auto-immune plasma cells into pathogenic long-lived plasma cells in the spleen that was not present before treatment. It has been reported that refractory ITP is related to the presence of long-lived plasma cells, which are resistant to steroids and immunosuppressants, including rituximab.
These findings lead to the hypothesis that therapy directed against plasma cells may help overcome treatment resistance. At least in a proportion of patients, treatment resistance is caused by CD20 negative long-lived plasma cells.
This study aims to investigate the efficacy, the optimal number of treatments, and safety of anti-CD38 antibody daratumumab steroid-refractory or steroid-dependent in ITP patients who fail to respond to at least one previous second-line therapy, including rituximab and/ or TPO agonist.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||The first 3 patients will be included in the safety run-in phase. The next 9 patients will be included in cohort 1 to receive 8 weekly injections. If the response rate is less than 100%, the next 9 patients will be included in cohort 2 to receive 8 weekly injections followed by 2 bi-weekly injections.|
|Masking:||None (Open Label)|
|Official Title:||Daratumumab as a Treatment for Adult Immune Thrombocytopenia (The DART Study)|
|Actual Study Start Date :||January 21, 2021|
|Estimated Primary Completion Date :||January 20, 2024|
|Estimated Study Completion Date :||December 20, 2024|
Experimental: Intervention ( safety run-in, cohort 1, cohort 2)
Safety run-in( 3 patients): daratumumab once a week x 4 doses. If no worsening of thrombocytopenia can be attributed to study treatment or any other life-threatening events, the study will proceed to the main part.
Cohort 1 ( 9 patients): daratumumab once a week x 8 doses
If response is <100%:
Cohort 2 ( 9 patients): daratumumab once a week x 8 doses followed by daratumumab every 2 weeks x 2 doses
Drug: Daratumumab Injection
subcutaneious daratumumab administration
Other Name: Darzalex
- to evaluate of response after daratumumab treatment [ Time Frame: 12-16 weeks ]Response defined as platelet count >50x109/L in 2 measurements (taken at least 24 hours apart) during week 12 for cohort 1 and during week 16 for cohort 2 (after first study drug injection) without having received rescue therapy, having had dose increment of TPO-RA or corticosteroids during the study period.
- safety of daratumumab [ Time Frame: 24 weeks ]incidence, severity and relationship of treatment emergent adverse events
- time to response [ Time Frame: 12-16 weeks ]Time to response defined as time from first daratumumab injection to first platelet count >50 X 109/L
- duration of response [ Time Frame: 24 weeks ]defines as median number of weeks with platelet count >50x109/L between end of treatment and end of study/ week 24 without having received rescue therapy or having had dose increment of corticosteroids in the 4 weeks prior to the first platelet count >50x109/L
- time to treatment failure [ Time Frame: 24 weeks ]defines as first platelet count <30x109/L or administration of any platelet elevating therapy after achieving response
- incidence of anti-drug antibodies (ADA) against daratumumab [ Time Frame: 24 weeks ]ADA
- measurement of HRQoL and fatigue [ Time Frame: 24 weeks ]measurement of HRQoL and fatigue using SF36 and MFI-20 questionnaire before daratumumab therapy, at week 8 for safety run-in, at week 12 for cohort 1, at week 16 for cohort 2 and at study week 24 for all patients in the study. Assess of difference in HRQoL and fatigue between non-responders and responders prior to and after daratumumab treatment
- measurements of antibodies [ Time Frame: 24 weeks ]level of anti-GPIIb/IIIa and Ib antibodiesbefore daratumumab therapy and at study week 24
- analysis of platelet bound antibodies and functional testing of immunocompetent cells [ Time Frame: 24 weeks ]analysis of platelet bound antibodies and functional testing of immunocompetent cells in peripheral blood and bone marrow before daratumumab therapy and at study week 24
- measurements of various subsets of immunocompetent cells [ Time Frame: 24 weeks ]characterization of various subsets of immunocompetent cells in the bone marrow and blood before daratumumab therapy and at study week 24
- correlation between response and changes in antibody levels or of immunocompetent cells. [ Time Frame: 24 weeks ]identify whether or not changes to antibody levels or of immunocompetent cells correlate with clinical response
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04703621
|Contact: Waleed Ghanima, PhD||+47 firstname.lastname@example.org|
|Contact: Christina Roaldsnes||+47 email@example.com|
|Odense University Hospital||Not yet recruiting|
|Odense, Denmark, 5000|
|Contact: Henrik Fredriksen, MD, PhD +45 65411158 Henrik.Frederiksen@rsyd.dk|
|Henri Mondor University Hospital||Not yet recruiting|
|Contact: Marc Michel, PhD +33 (0)1 49 81 20 60 firstname.lastname@example.org|
|Haukeland University Hospital||Recruiting|
|Contact: Galina Tsykunova, MD +47 90670517 email@example.com|
|Ostfold Hospital Trust||Recruiting|
|Grålum, Norway, 1714|
|Contact: Christina Roaldsnes +47 41267921 firstname.lastname@example.org|
|Akershus University Hospital||Not yet recruiting|
|Contact: Hoa Thi Tuyet Tran, PhD +4767966490 Hoa.Thi.Tuyet.Tran@ahus.no|
|Oslo University Hospital||Active, not recruiting|
|Principal Investigator:||Waleed Ghanima, PhD||Ostfold Hospital Trust|