The DART Study- Daratumumab Treatment in ITP

NCT04703621 | Unknown Phase 2 DMC

• 1 other identifier: RGCH005
• Study Type: interventional
• Target: 21
• Locations: 3 countries
• Sites: 6

Brief Summary

A multicenter clinical, open-label total dose-escalating phase II study with safety run-in to explore the clinical activity, total dosage, and safety of daratumumab in adult ITP patients who have not responded adequately or relapsed after corticosteroids and at least one second-line therapy including rituximab and/or TPO-RA.

Conditions

ITP

Outcome Measures

Primary Outcomes (2)

• to evaluate of response after daratumumab treatment

  Response defined as platelet count ≥50 x109/L in 2 measurements (taken at least 24 hours apart) during week 12 for safety run-in 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.

  12-16 weeks

• safety of daratumumab

  incidence, severity and relationship of treatment emergent adverse events

  24 weeks

Secondary Outcomes (7)

• duration of respons (DOR)

  12-16 weeks

• time to treatment failure (TTF)

  minimum 24 weeks

• measurement of HRQoL and fatigue

  24 weeks

• measurements of antibodies

  24 weeks

• analysis of platelet bound antibodies and functional testing of immunocompetent cells

  24 weeks

Study Arms (1)

Intervention ( safety run-in, cohort 1, cohort 2)

EXPERIMENTAL

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

Interventions

Daratumumab Injection DRUG

subcutaneious daratumumab administration

Also known as: Darzalex

Intervention ( safety run-in, cohort 1, cohort 2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged ≥18 years.
• Signed and dated written informed consent.
• Females of child-bearing potential accepting to follow effective contraceptive methods for at least 24 weeks following the administration of first daratumumab injection. A man who has not had a vasectomy and who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control e.g., a condom with spermicidal foam/film/gel/cream/suppository, and all men must also not donate sperm during the study and for 3 months following discontinuation of Daratumumab

You may not qualify if:

• Pregnancy or lactation.
• Surgery planned within the 3 next months.
• Secondary ITP: ITP associated with lymphoma, chronic lymphocytic leukemia, drug induced or ITP secondary to autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, common variable immune deficiency, human immunodeficiency virus, or hepatitis C.
• Concomitant autoimmune hemolytic anemia.
• Known allergy and/or sensitivity or contraindication to daratumumab.
• Current active malignancy likely to require chemotherapy or surgical treatment during the study period or within one year after the start of the study treatment.
• Patients with history of poor compliance or history of alcohol/drug abuse or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent.
• Patient unable to attend all the visits planned for the trial.
• Positive at screening for hepatitis B virus (HBV) surface and core antibodies unrelated to vaccination:
• patients with positive HBV surface antigen (HbsAg) are not eligible
• patients who are HbsAg negative and HBV core antigen antibody positive (HBcAb) will be tested for HBV surface antibody (HBsAb) and HBV DNA. If HBsAb titer is \>1000 IU/ml, patients may be enrolled. Monthly HBV DNA monitoring will be required while on treatment and for the 6 months after the last dose of the study drug.
• patients who are HBcAb positive, HBsAg negative with HBsAb titer \<100 IU/ml or negative, are not eligible.
• Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \<50% of predicted normal. Note that FEV1 testing is required for participants suspected of having COPD.
• Known moderate or severe persistent astma within the past 2 years, uncontrolled asthma of any classification.
• Patient participating in another clinical trial with an investigational drug.

Sponsors & Collaborators

• Ostfold Hospital Trust: lead
• Haukeland University Hospital: collaborator
• Oslo University Hospital: collaborator
• University Hospital, Akershus: collaborator
• Henri Mondor University Hospital: collaborator
• Odense University Hospital: collaborator

Study Sites (6)

Odense University Hospital

Odense, 5000, Denmark

Location

Henri Mondor University Hospital

Créteil, France

Location

Haukeland University Hospital

Bergen, Norway

Location

Ostfold Hospital Trust

Grålum, 1714, Norway

Location

Akershus University Hospital

Oslo, Norway

Location

Oslo University Hospital

Oslo, Norway

Location

Related Publications (1)

• Tsykunova G, Holme PA, Tran HTT, Frederiksen H, Tjonnfjord E, Munthe LA, Drivet E, Kared H, Sorvoll IH, Ahlen MT, Mahevas M, Michel M, Bussel J, Kuter DJ, Anderson Tvedt TH, Ghanima W. Safety and efficacy of daratumumab in immune thrombocytopenia. Blood Adv. 2026 Jan 13;10(1):143-154. doi: 10.1182/bloodadvances.2025017279.

  PMID: 40763272 DERIVED

MeSH Terms

Interventions

daratumumab

Study Officials

• Waleed Ghanima, PhD

  Ostfold Hospital Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: December 4, 2020
• First Posted: January 11, 2021
• Study Start: January 21, 2021
• Primary Completion: April 1, 2024
• Study Completion: December 1, 2024
• Last Updated: April 9, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1); NO (4); DK (1)