Multiple Myeloma and Minimal Residual Disease MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Darzalex®
Product Name: Daratumumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: DARATUMUMAB
CAS Number: 945721-28-8
Other descriptive name: Daratumumab
Sponsors
Polish Myeloma Consortium
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with diagnosed symptomatic MM who have completed one or two prior lines of therapy; single or tandem autologous stem cell transplant is not considered a separate line of therapy and is not mandatory; a) and have achieved at least PR to last line of therapy, and who experience asymptomatic biochemical progression not meeting criteria for SPR (substudy PREDATOR-BR) b) and have achieved CR with negative MRD to the last line of therapy and i) remain in CR MRD negative based on MRD flow cytometry assessment at screening (repeating MRD evaluation is not needed if CR MRD negative status in bone marrow sample using flow cytometry with sensitivity of at least 10-5 was confirmed not earlier than 3 months before inclusion to the study) or ii) have CR with positive flow cytometry MRD status based on MRD flow cytometry assessment at screening. Those patients will be randomized directly after screening without entering MRD observation phase. (PREDATOR-MRD substudy) 2. Males and females =18 years of age. 3. Life expectancy of more than 3 months. 4. ECOG performance status of 0-2. 5. Adequate hepatic function, with bilirubin =1.5 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 x ULN. 6. ANC =1.0 x 109/L, hemoglobin =8 g/dL, platelet count =75 x 109/L. 7. Calculated creatinine clearance (by Cockroft-Gault) =50 mL/min (this equation is as follows: Creatinine clearance in ml/min: (140 – age) x body weight (kg) / 72 x plasma creatinine (mg/dL); multiplied by 0.85 for women) or serum creatinine below 2 g/dL. 8. Negative pregnancy test (serum ßHCG) for women of childbearing potential (including pre-menopausal women who have had a tubal ligation) and for all women not meeting the definition of postmenopausal (= 24 months of amenorrhea), and who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy. For all other women, documentation must be present in medical history confirming that the patient is not of childbearing potential. 9. FCBP must agree to use 2 reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse during the study. 10. Male subjects must agree to use a latex condom during sexual contact with females of childbearing potential while participating in the study and for at least 28 days following discontinuation from the study even if he has undergone a successful vasectomy. 11. Voluntary written informed consent. 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 85 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 189
Exclusion criteria
Exclusion criteria: 1. Potential subjects with evidence of progressive disease (CRAB symptoms) as per IMWG criteria. 2. Patient with SPR - significant paraprotein relapse defined as doubling of the M-component in two consecutive measurements separated by 470 msec on a 12-lead ECG during screening. 16. Patient who in investigator’s opinion is unable to comply with the protocol requirements. 17. Uncontrolled hypertension or diabetes. 18. Acute infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to enter the study. 19. Active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible. 20. Non-hematologic malignancy or non-myeloma hematologic malignancy within the past 3 years except a) adequately treated basal cell, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the cervix, or prostate cancer < Gleason Grade 6 with stable prostate specific antigen levels or cancer considered cured by surgical resection alone. 21. Any clinically significant medical disease or condition that, in the Investigator’s opinion, may interfere with protocol adherence or a subject’s ability to give informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare EFS between daratumumab arm and observation arm after randomization of patients with biochemical relapse of MM and patients with reappearance of MRD in MM.;Secondary Objective: 1.To assess the efficacy of daratumumab treatment in MM patients who experienced a biochemical relapse and patients who experienced MRD reappearance 2.To assess the time to MRD neg. achievement 3.To determine the rate of MRD neg. disease at completion of treatment with daratumumab (at 19 months) 4.To evaluate the safety and tolerability of daratumumab in MM patients who experienced a biochemical relapse and patients who experienced MRD reappearance 5.To evaluate and compare changes in quality of life of subjects in the daratumumab therapy cohort with those in the observation cohort. 6. To evaluate and compare quality of life od subjects treated daratumumab IV vs. daratumumab sc 7.To compare overall survival between arms 8. To determine the rate of MRD neg. disease at completion of treatment with daratumumab 9.To assess the time to MRD neg. achievement on treatment with daratumumab 10.To assess the time from MRD reappearance to clinical progression or SPR in observation arm ;Primary end point(s): To compare (EFS) between daratumumab arm and observation arm after randomization of patients with biochemical relapse of MM. To compare (EFS) between daratumumab arm and observation arm after randomization of patients with reappearance of MRD in MM.;Timepoint(s) of evaluation of this end point: EFS defined as the time from randomization date to the date of development of clinical relapse defined as development of CRAB symptom (s), SPR or death from any cause. Clinical relapse is defined as requiring one or more of the following direct indicators of increasing disease and/or end-organ dysfunction (CRAB features) that are considered related to the underlying plasma cell proliferative disorder. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): SPR, CRAB or death. Overall response rate (ORR) as determined by Investigator evaluation, defined as the percentage of subjects achieving an objective response (i.e., partial response or better), using the IMWG Consensus Panel 1 response criteria. ;Timepoint(s) of evaluation of this end point: The response will be assessed every four weeks on treatment. - Incidence and severity of AE. - Incidence and severity of SAE. - Incidence and severity of infusion reactions. - Incidences of Grade 3 and 4 infections and myelosuppression (anemia, neutropenia, thrombocytopenia). - Changes from baseline in QOL measures assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). - Change of ECOG (Eastern Cooperative Oncology Group) performance status. - International Staging System ISS (ß2 – microglobulin, Serum albumin) - Cytogenetics by fluorescent in situ hybridization (FISH): del(17p13), t(4;14), t(14;16) | — |
Countries
Poland
Contacts
Public ContactPolish Myeloma Consortium
Polish Myeloma Consortium
Outcome results
None listed