Multiple Myeloma: cohort 1: dialysis dependent patients
Conditions
Interventions
Trade Name: DARZALEX
Product Name: Darzalex
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Daratumumab
CAS Number: 945721-28-8
Concentration unit: mg/ml milligram(s)/millilitre
Conce
Sponsors
Medical University Innsbruck
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients in need of therapy with untreated MM and myeloma induced renal failure either requiring dialysis, or with renal insufficiency with an estimated creatinine clearance 3 months • ECOG = 3 (ECOG 3 solely defined by being bedridden or in need of care due to dialysis catheter and/or elevated retention parameters and/or other myeloma induced impairment, e.g. osteolytic bone pain). Pat. must have had ECOG = 2 before myeloma diagnosis • Absolute neutrophil count (ANC) > 1.000/mm3 and platelet count > 50.000/mm3. Platelet transfusions to help patients meet eligibility criteria are allowed within 3 days before study enrollment. • Total bilirubin = 2 x ULN • ALT and AST = 3 x ULN • Disease free of prior malignancies for = 2 years with exception of curatively treated basal cell, squamous cell carcinoma of the skin, or carcinoma “in situ” of the cervix or breast if they have undergone complete resection. Female patients who: • Are older than 50 years and postmenopausal for at least 1 year before the screening visit, OR • Are surgically sterile, OR • If they are of childbearing potential, agree to practice 2 effective methods of contraception at the same time, from 4 weeks before starting study therapy through 90 days after the last dose of study drug, OR • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception). • Are informed and understand the possible consequences of the teratogenic potential of pomalidomide. Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to one of the following: • Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR • Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.) • Are informed and understand the possible consequences of the teratogenic potential of pomalidomide 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 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 35
Exclusion criteria
Exclusion criteria: • Female patients who are lactating or have a positive serum pregnancy test during the screening period •Previous anti-myeloma treatment within the last 21 days prior to baseline visit (cycle 1 / day 1), except corticosteroid therapy (<=160 mg dexamethasone or corticosteroid dose equivalent for a maximum of 5 days prior to d1c1) • Major surgery within 14 days before enrollment • Radiotherapy within 14 days before enrollment, except local radiation for pain and/or instable bones. • Clinical evidence of central nervous system involvement • Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months • Systemic treatment, within 14 days before the first dose of study medication, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of CYP3A4 (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A4 inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort (interference with the metabolization of pomalidomide). • Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive • Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent • Known gastrointestinal (GI) disease or GI procedure that could interfere with oral absorption or tolerance of difficulty swallowing. • Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with basal cell, squamous cell carcinoma of the skin, or carcinoma “in situ” of the cervix or breast with are not excluded if they have undergone complete resection • Patient has = grade 3 peripheral neuropathy. • Participation in other interventional clinical trials, including those with other investigational agents not included in this trial, within 30 days of the start of this trial and throughout the duration of this trial. • Pre-existing documented severe renal impairment (before suspected MM diagnosis) with an eGFR of <30 ml/min/1.73 m2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the safety and toxicity and the rate of renal recovery in newly diagnosed patients with MM induced renal failure receiving daratumumab in combination with carfilzomib, pomalidomide and dexamethasone for 4 cycles.;Secondary Objective: To determine the overall response rate (ORR) in newly diagnosed patients with MM induced renal failure receiving daratumumab in combination with carfilzomib, pomalidomide and dexamethasone for 4 cycles. ORR will be assessed according International Myeloma Working Group (IMWG) criteria, including Minor Response (MR) according to European Society for Blood and Bone Marrow Transplantation (EBMT) criteria. To determine progression free survival (1-Year PFS) in newly diagnosed patients with MM induced renal failure receiving daratumumab in combination with carfilzomib, pomalidomide and dexamethasone for 4 cycles.;Primary end point(s): Feasability 1.) Dialysis dependent patients: To determine the rate of patients becoming dialysis independent after induction treatment in patients with myeloma induced renal failure requiring dialysis and receiving induction treatment with 4 cycles of daratumumab in combination with carfilzomib, pomalidomide and dexamethasone (DCPD) 2.) Patients not dialysis dependent: To determine the rate of patients achieving improvement of their renal function after induction treatment. Patients receive induction treatment with 4 cycles of daratumumab in combination with carfilzomib, pomalidomide and dexamethasone (DCPD) renal recovery defined as: a) becoming independent from hemodialysis if dialysis dependent at diagnosis. b) renal response in patients with baseline glomerular filtration rate (GFR) 100%, i.e.: from stage V (GFR < 15ml/min) to stage III (GFR 30 – <60 ml/min) Defined by a measurement at baseline and at the end of induction treatment.;Timepoint(s) of evaluation of this end point: End of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints are: Progression free survival at 1 year (PFS)in months, defined as the time from day 1 of cycle 1 to the date of first documentation of disease progression based on IMWG criteria or death due to any cause, whichever occurs first. Overall response rate (ORR) being described as complete response, near complete response, very good partial response, partial response, minor response, stable disease, progressive disease. ORR will be assessed according to International Myeloma Working Group (IMWG) criteria, including Minor Response (MR) according to European Society for Blood and Bone Marrow Transplantation (EBMT) criteria. Time to first response defined as days from day 1 of cycle 1 to the first documented response. Time to best response defined (days) from day 1 of cycle 1 to the best documented response. Recording of AE´s, SAE´s, ECOG performance status, assessment of clinical laboratory values. Minimal residual disease will be performed in bone marrow samples (only in patients achieving complete response after cycle 4) according to the Euroflow-protocol (FACS-Analysis) with a sensitivity of 10-5);Timepoint(s) of evaluation of this end point: End of trial | — |
Countries
Austria
Contacts
Public ContactPrinicpal Investigator
Medical University Innsbruck
Outcome results
None listed