Immune thrombocytopenia MedDRA version: 23.0 Level: LLT Classification code 10021245 Term: Idiopathic thrombocytopenic purpura System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Trade Name: Darzalex
Pharmaceutical Form: Solution for injection
INN or Proposed INN: DARATUMUMAB
CAS Number: 945721-28-8
Current Sponsor code: JnJ 54767414
Other descriptive name: HUMAX-CD38
Concentr
Sponsors
Ostfold Hospital Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female aged =18 years. 2. Primary ITP with a platelet count of =30 X 109/L measured within 2 weeks prior to inclusion with failure to achieve response or relapse after corticosteroid therapy, and at least one second-line therapy including rituximab (last infusion =24 weeks before study inclusion) and/or TPO-RA. The dose of steroids or/and TPO-RAs (romiplostim, eltrombopag and avatrombopag) has not been changed during the last 2 weeks preceding the inclusion. For the safety run-in phase, a platelet count of 15-30 X 109/L will be required. 3. Signed and dated written informed consent. 4. 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. condom with spermicidal foam/film/gel/cream/ suppository, and all men must also not donate sperm during the study and for 3 month following discontinuation of Daratumumab (for details see appendix VII). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 11 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Patients with active bleeding during the last 7 days prior to inclusion. Active bleeding is defined as any clinically overt hemorrhage (including radiologically diagnosed bleeding) with ongoing hemoglobin fall or bleeding requiring immediate intervention. 2. Pregnancy or lactation. 3. Surgery planned within the 3 next months. 4. 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. 5. Concomitant autoimmune hemolytic anemia. 6. Known allergy and/or sensitivity or contraindication to daratumumab. 7. 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. 8. 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. 9. Patient unable to attend all the visits planned for the trial. 10. 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 (HBcAg) 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. 11. 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. 12. Known moderate or severe persistent astma within the past 2 years, uncontrolled asthma of any classification. 13. Patient participating in another clinical trial with an investigational drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Objectives safety run-in •to assess safety and tolerability of daratumumab in patients with ITP.- Other objectives as main study. Objectives main part •to determine the efficacy of treatment with daratumumab defined as response at week 12 for safety run-in and cohort 1, and week 16 for cohort 2. •to characterize the safety of daratumumab in patients with ITP. ;Secondary Objective: Secondary objectives: -to assess rates of sustained response (sR) at week 24.-to assess the duration of response (DOR) -•To determine the time to treatment failure (TTF) -•To assess bleeding complications during the study. Exploratory objectives: •to characterize immunological effects of daratumumab treatment: -to characterize various subsets of immunocompetent cells in the bone marrow and blood before and during daratumumab therapy and at study week 24 (only peripheral blood). • -to identify a potential biomarker (whether or not changes to antibody levels or levels of immuno-competent cells correlate with response). • to determine HRQoL and level of fatigue before and after treatment with daratumumab and to assess difference in HRQoL and fatigue between patients with or without response, prior to and after daratumumab.•To assess time from first dose of study medication to first platelet count >50x109/L•To assess rates of complete and partial response (CR) to daratumumab.;Primary end point(s): End points safety run-in Safety and tolerability defined as: 1.Treatment-emergent adverse events/ serious adverse events (TEAEs/SAE) incl. hematological treatment related adverse events. 2.Incidence of platelet counts decrease during the treatment and up to 2 weeks after the treatment. 3.Incidence of abnormal changes from baseline in laboratory values per CTCAE criteria V 5.0 (e.g., hematology, chemistry). End points main part •response after daratumumab treatment defined as: o•Safety run in and Cohort 1: proportion of patients who achieve platelet count =50x109/L in 2 measurements | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary end points: • Sustained response (sR) defined as platelet count = 50x109/L in 2 measurements (taken at least 24 hours apart) measured at study week 24 (+/-2 weeks) without having received any platelet elevating therapy or having had dose increment of TPO-RA and/or corticosteroids. • DOR defined as the duration of sustained platelet count =50x109/L without having received any platelet elevating therapy or having had dose increment of TPO-RA and/or corticosteroids. Duration will not consider the 4 weeks following the last daratumumab injection in the study. . Loss of response is defined as platelet count 1. -Maximum severity on the World Health Organisation (WHO) bleeding scale -Change in Khellaf score measured at the day of first daratumumab administration and at week 24 evaluation. Exploratory end points: • Level of anti-GPIIb/IIIa and Ib antibodies before daratumumab therapy and at study week 24 for all included patients. • Analysis of platelet bound antibodies and functional testing of immunocompetent cells in peripheral blood and bone marrow before, during daratumumab therapy and at study week 24 (only peripheral blood). Platelet bound antibodies will also be tested at study week 8 (safety run-in), week 12 (cohort 1), at study week 16 (cohort 2). • Measurement of HRQoL and fatigue using SF36v1 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.-• Time to first platelet count >50x109/L measured from the day of first administration of study medication. • Rates of complete response defined as a proportion of patients with platelet count >100x 109/L determined at week 12 for the safety run-in and cohort 1, week 16 for cohort 2 and week 24 for all patients (requires two measurements taken at least 24 hours apart) without having received rescue therapy after week 8, or having had dose increment of cortico | — |
Countries
Denmark, Norway
Contacts
Public ContactSykehuset Østfold
Ostfold Hospital Trust
Outcome results
None listed