Daratumumab in Combination with Carfilzomib, Pomalidomide and Dexamethasone in patients with myeloma induced acute renal failure

Prior treatment

• 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
• 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
• 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
• 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)

Other illness

• 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.
• 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
• 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

Lab values

• Female patients who are lactating or have a positive serum pregnancy test during the screening period
• Pre-existing documented severe renal impairment (before suspected MM diagnosis) with an eGFR of <30 ml/min/1.73 m2.

Other

• Patient has ≥ grade 3 peripheral neuropathy
• Clinical evidence of central nervous system involvement

• Patients in need of therapy with untreated multiple myeloma and myeloma induced renal failure either requiring dialysis, or with renal insufficiency with an estimated creatinine clearance <30 ml/min.
• 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
• Female patients who Are surgically sterile, OR
• Female patients who 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
• Female patients who 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)
• Female patients who 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 practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug
• Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject
• Male patients are informed and understand the possible consequences of the teratogenic potential of pomalidomide
• Male or female patients 18 years to 70 years
• Voluntary written consent must be given before start of antimyeloma treatment, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
• Patients must have measurable disease defined by at least 1 of the following criteria: Serum M-protein ≥ 10g/l Urine M-protein ≥ 200mg/24h sFLC assay: involved serum light chain ≥ 10mg/dl provided that FLC ratio is abnormal
• Life expectancy > 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