Primary plasma cell leukemia MedDRA version: 20.0 Level: LLT Classification code 10035223 Term: Plasma cell leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Darzalex 1.800mg
Product Name: Daratumumab co-formulated with recombinant human hyaluronidase (rHuPH20)
Product Code: JnJ 54767414
Pharmaceutical Form: Solution for injection
INN or Propos
Sponsors
Hellenic Society of Haematology (HSH)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Female or male patients of any race or ethnicity, aged between 18 and 80 years (inclusive) at the time of signing the ICF. 2.Patients newly diagnosed with documented pPCL as defined by the current IMWG criteria for PCL and MM [5,34]: 2.1 Documented presence of =5% PBPCs and/or absolute number =0.5 × 103/µL (by flow cytometry) 2.2 Clonal BMPCs =10% or biopsy-proven bony or extramedullary plasmacytoma (EMP) 2.3 At least one of the following myeloma defining events (CRAB or malignancy biomarkers criteria - Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically (one or more of the following): a) Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal (ULN) or >2.75 mmol/L (>11 mg/dL) b) Renal insufficiency: Creatinine clearance (CrCl) 177 µmol/L (>2 mg/dL) c) Anemia: hemoglobin value of >20 g/L below the lower limit of normal (LLN), or a hemoglobin value 1 focal lesions on MRI studies (each focal lesion must be 5 mm or more in size). 3. Measurable disease by protein electrophoresis as defined by any of the following: 3.1 Serum M-protein level: - For IgG MM: =1.0 g/dL or urine M-protein level =200 mg/24 hours - For IgA, IgE and IgM MM: =0.5 g/dL or urine M-protein level =200 mg/24 hours - For IgD MM: =0.05 g/dL or urine M-protein level =200 mg/24 hours 3.2 Light chain MM without measurable disease in the serum or the urine: sFLC =10 mg/dL (involved light chain) and abnormal sFLC ?/? ratio. 4. Patients for whom high-dose therapy, with or without stem cell transplantation, is part of the intended treatment plan. 5. Patient not currently or previously treated with any systemic therapy or stem cell transplant for any plasma cell dyscrasia, apart from a short course of corticosteroid therapy (equivalent of dexamethasone 40 mg/day for up to 4 days). 6. Adequate bone marrow function as determined by the following: 6.1 Hemoglobin =7.0 g/dL [=4.34 mmol/L; prior red blood cell (RBC) transfusion or recombinant human erythropoietin use is permitted] 6.2 Absolute neutrophil count (ANC) =1.0 x 109/L 6.3 Platelet count =50 x 109/L if disease involvement in bone marrow is >50%; otherwise =75% x 109/L. 7. Adequate liver function as determined by the following: 7.1 Serum Aspartate Transaminase (AST) =2.5 x ULN 7.2 Serum Alanine Aminotransferase (ALT) =2.5 x ULN 7.3 Total bilirubin =1.5 x ULN 8. Adequate renal function as determined by estimated CrCl =20 mL/min 9. Performance status (PS) according to (ECOG) 0-3 10. If females of childbearing potential (FCBP)*, the following apply: 10.1 Willingness to use an acceptable form of birth control 10.2 They must agree not to donate eggs (ova, oocytes) 10.3 They must have 2 negative serum or urine pregnancy tests; 11. If male subjects of reproductive potential who are sexually active with FC
Exclusion criteria
Exclusion criteria: 1. Patients with secondary PCL. 2. Prior or concurrent invasive malignancy (other than PCL) within 5 years of date of study treatment initiation except for the following: 2.1 Malignancy treated with curative intent and with no known active disease present for =3 years before study treatment initiation. 2.2 Adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix or breast, incidental histologic finding of prostate cancer (T1a or T1b) or other non-invasive lesion that, as per Investigator’s judgement, is considered cured with minimal risk of recurrence over the next 3 years. 3. Radiation therapy within 14 days before study treatment initiation. 4. Plasmapheresis within 28 days before study treatment initiation. 5. Exhibiting clinical signs of meningeal or central nervous system involvement by PCL. 6. Patients with peripheral neuropathy or neuropathic pain Grade 2 or higher 7. Concurrent systemic amyloidosis, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and/or skin changes), active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease, and any other medical condition/disease that is likely to interfere with the study procedures or results, or that in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. 8. Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second [FEV1] 470 msec (except for subjects with pacemaker) 11.7 Screening transthoracic echocardiogram (TTE) showing left ventricular ejection fraction (LVEF) <40% (screening TTE is required only for subjects aged = 65 years). 12. Receipt of a strong CYP3A4 inducer (e.g., rifampicin, carbamazepine, phenytoin, phenobarbital and St. John’s Wort) within 5 half-lives prior to study treatment initiation. 13. Known allergies, hypersensitivity, or intolerance to boron or mannitol, corticosteroids, monoclonal antibodies or human proteins, or their excipients (refer to respective SmPCs and Investigator's Brochure [IB]), or known sensitivity to mammalian-derived products. 14. Gastrointestinal disease that may significantly affect the absorption of oral drugs as per Investigator’s discretion. 15. Vaccination with live attenuated vaccines within 4 weeks of study treatment initiation. 16. Major surgery within 2 weeks before study tre
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the efficacy of the alternating D-PAD/D-CVD induction regimen followed by D-CVD consolidation regimen and maintenance with daratumumab monotherapy, in terms of PFS, in the first-line setting of pPCL.;Secondary Objective: •To evaluate the ORR post-induction, post-ASCT, post- consolidation, and post-maintenance treatment •To evaluate the rates of VGPR post-induction, post-ASCT, post-consolidation, and post-maintenance treatment •To evaluate the rates of complete response (CR) or better post-induction, post-ASCT, post-consolidation, and post-maintenance treatment •To evaluate time to response (PR or better) •To evaluate time to VGPR or better •To evaluate time to CR or better •To evaluate duration of response (PR or better) •To evaluate duration of CR or better •To estimate the PFS rate at 12 and 24 months post-induction treatment initiation •To evaluate time to disease progression (TTP) •To evaluate time to next treatment (TTNT) •To evaluate the post-induction, post-consolidation and overall MRD negativity rate •To evaluate the OS as well as the OS rates at 12 and 24 months post-induction treatment initiation •To assess the safety and tolerability of the study treatment.;Primary end point(s): The primary objective of this study is to evaluate the efficacy of the alternating D-PAD/D-CVD induction regimen followed by D-CVD consolidation regimen and maintenance with daratumumab monotherapy, in terms of PFS, in the first-line setting of pPCL.;Timepoint(s) of evaluation of this end point: PFS: Duration from the date of induction treatment initiation to the date of first documented evidence of PD (assessed by the IMWG criteria) or death, whichever occurs earlier | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportions of patients achieving PR or better, VGPR or better, and sCR or CR (as determined by the IMWG criteria) ;Timepoint(s) of evaluation of this end point: - After 6 cycles of induction treatment (and before ASCT for the transplant-eligible patients) - Following ASCT and before consolidation initiation (applicable for transplant-eligible patients) - At the end of consolidation treatment (Cycle 8) - At the end of the maintenance treatment | — |
Countries
Greece
Contacts
Public ContactEirini Katodritou
Hellenic Society of Haematology
Outcome results
None listed