About this trial
The goal of this clinical trial is to learn if drug daratumumab works to treat kidney diseases other than AL-amyloidosis that fall under the category of monoclonal gammopathy of renal significance (MGRS).
The main questions it aims to answer are:
Does daratumumab have an effect on the patients' renal function or the amount of proteinuria?
Does daratumumab have an effect on the hematological endpoints evaluated by minimal residual disease (MRD) and the difference between involved and uninvolved free light chain (dFLC)?
Also changes in quality of life (according to EORTC QLQ-C30) and mechanism of complement system activation are evaluated. The number of patiets with partial or very good partial hematological remission and the number of patients with adverse events related to daratumumab are also recorded.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Males or females ≥ 18 years of age
Subject has provided informed consent prior to initiation of the study or subject's legally acceptable representative has provided informed consent prior to the study when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.
Renal biopsy confirmed MGRS-disease
Renal biopsy must not be older than 3 months before informed consent. However, if renal biopsy is older than 3 mo and the study team is convinced that major histological changes have not occurred, a biopsy older than that can exceptionally be accepted.
Disqualifiers
Myeloma or systemic AL amyloidosis (smoldering myeloma sized plasma cell clone is allowed when in association with a documented MGRS condition and AHL amyloidosis and AH amyloidosis are included)
Cancer that requires treatment,
MGRS related to B-cell malignant disorders,
Known HIV infection, active hepatitis C infection (subjects with hepatitis C that achieve a sustained virologic response after antiviral therapy are allowed), or hepatitis B infection (subjects with hepatitis B surface antigen or core antibody that achieve sustained virologic response (PCR negativity in HBVNh) with antiviral therapy are permitted with a requirement for regular monitoring for reactivation for the duration of treatment on the study),
Trial design
Parallel
Treatments tested in this trial
Daratumumab
DrugAll patients will receive either fixed-dose daratumumab as a single agent therapy or fixed-dose daratumumab combined with stem cell transplantation.
Treatment groups
Trial outcomes
Primary outcomes
Rate of complete renal remission or partial renal remission and proteinuria and eGFR at EOT.
Complete renal remission (proteinuria \<500 mg/d and \<15% decline in baseline eGFR) Partial renal remission (\>50% reduction in 24-h proteinuria and \< 30% decline in eGFR)
Secondary outcomes
Rate of complete renal remission or partial renal remission and proteinuria and eGFR after 6 cycles of daratumumab.
Complete renal remission (proteinuria \<500 mg/d and \<15% decline in baseline eGFR) Partial renal remission (\>50% reduction in 24-h proteinuria and \< 30% decline in eGFR)
Rate of negativity of bone marrow minimal residual disease (MRD) after 6 and 12 cycles of daratumumab.
Number of patients with complement dysregulation-mediated renal damage caused by paraprotein.
Number of patients in end-stage renal disease or with eGFR decline > 50 %.
Sponsors and contacts
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Helsinki University Central Hospital
Lead sponsor
Janssen, L.P. - Investigator Initiated Studies Program
Collaborator