Relapsed or Refractory Multiple Myeloma. Multiple myeloma
Conditions
Interventions
Intervention 1: Intervention group:- Daratumumab (manufactured by CinnaGen Co.) 16 mg/Kg intravenous infusion once weekly (cycles 1-2), every two weeks (cycles 3-6), and every four weeks (cycles 7 and
Sponsors
CinnaGen Company
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Age of at least 18 years old at the time of randomization Willingness for signing and having signed the written informed consent form Diagnosis of multiple myeloma per IMWG criteria:3.1. Clonal bone marrow plasma cells =10% at some point in their disease history or presence of a biopsy-proven plasmacytoma3.2. Measurable disease as defined by any of the following:3.2.1. IgG multiple myeloma: Serum monoclonal paraprotein (M-protein) level =1.0 g/dL or urine M-protein level =200 mg/24h3.2.2. IgA, IgM, IgD, or IgE multiple myeloma: serum M-protein level =0.5 g/dL or urine M-protein level =200 mg/24h Subject must have received at least one prior line of therapy for multiple myeloma.A line of therapy consists of 1 complete cycle of a single agent, a regimen consisting of a combination of several drugs, or a planned sequential therapy of various regimens (eg, 3-6 cycles of initial therapy with bortezomib-dexamethasone followed by stem cell transplantation, consolidation, and lenalidomide maintenance is considered 1 line). Subject must have achieved a response (Partial Response or Better based on investigator’s determination) to at least one prior regimen. Subject must have progressive disease, based on investigator’s determination, on or after their last regimen Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
Exclusion criteria
Exclusion criteria: Subject has received daratumumab or other anti-CD38 therapies previously. Subject’s disease shows evidence of refractoriness to any dose of lenalidomide, defined either:2.1. Subjects whose disease progresses within 60 days of the last dose of lenalidomide; or2.2. Subjects whose disease is nonresponsive while on lenalidomide. Nonresponsive disease is defined as either failure to achieve at least a Minimal Response or development of PD while on lenalidomide. Subject has received anti-myeloma treatment within 2 weeks before the date of randomization. The only exception is emergency use of a short course of corticosteroids (equivalent of dexamethasone 40 mg/day for a maximum 4 days) before treatment. Subject has received more than two prior lines of therapy for multiple myeloma. Subject has received autologous stem cell transplant within 12 weeks before the date of randomization, or subject has previously received an allogeneic stem cell transplant (regardless of timing) Subject in need of stem cell transplant during the study period (in investigator’s opinion), or planning to undergo a stem cell transplant prior to disease progression in this study, ie, these subjects should not be enrolled in order to reduce disease burden prior to transplant. A history of malignancy (other than multiple myeloma) within 5 years before the date of randomization, with the exception of squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix, or a malignancy that in the opinion of the investigator is considered cured with minimal risk of recurrence within 5 years Subject has known meningeal involvement of multiple myeloma Known chronic obstructive pulmonary disease (COPD) of grade GOLD 3 (severe) or GOLD 4 (very severe) based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) Current uncontrolled persistent asthma in time of screening (per American Lung Association’s classification) Human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) seropositivity; This criterion is assessed via HBs-Ag, HBc-Ab, HCV-Ab, and HIV-Ab tests at screening. Subject has any of the following laboratory test results during the Screening Phase:12.1. Aspartate aminotransferase (AST) or alanine aminotransferase level (ALT) = 2.5 times the upper limit of normal (ULN)12.2. Alkaline phosphatase level = 2.5 × ULN12.3. Total bilirubin level = 1.5 × ULN, (except for Gilbert Syndrome: direct bilirubin 1.5 × ULN) Subject has known hypersensitivity to monoclonal antibodies or human proteins Subject has plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard differential), Waldenström’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, or amyloidosis Pregnant or nursing women, or female/male subject planning to become pregnant while enrolled in this study, within 4 weeks after the last dose of lenalidomide, or within 12 weeks after the last dose of daratumumab. Female and male subjects in the reproductive age must use reliable methods of contraception. Subject has received an investigational drug within 4 weeks before randomization (except for investigational anti-myeloma agents, which cannot be taken within 2 weeks prior to randomization, as described in exclusion criterion #3) Subject has had major surgery within 2 weeks before randomization, or will not have f
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of subjects who achieve Very Good Partial Response (VGPR) or better per IMWG criteria, within one year after treatment initiation. Timepoint: From randomization up to 12 months. Method of measurement: Response, based on International Myeloma Working Group (IMWG) criteria. | — |
Secondary
| Measure | Time frame |
|---|---|
| Duration of Response (DOR): The duration from the first documented VGPR or better per IMWG criteria, to the date of first documented progressive disease per IMWG criteria. Timepoint: From randomization up to 12 months. Method of measurement: Response, based on International Myeloma Working Group (IMWG) criteria.;Overall Survival (OS): Time from the randomization date to the date of the subject’s death due to any cause. Timepoint: From randomization up to 12 months. Method of measurement: Recording of the duration from the date of randomization to the date of the subject’s death due to any cause.;Overall Response Rate (ORR): The proportion of subjects who achieve Partial Response (PR) or better per IMWG criteria, within one year after treatment initiation. Timepoint: From randomization up to 12 months. Method of measurement: Response, based on International Myeloma Working Group (IMWG) criteria.;Time to Response (TTR): Time from the randomization date to VGPR or better per IMWG criteria. Timepoint: From randomization up to 12 months. Method of measurement: Response, based on International Myeloma Working Group (IMWG) criteria.;Time to progression (TTP): Time from the randomization date to progressive disease per IMWG criteria. Timepoint: From randomization up to 12 months. Method of measurement: Response, based on International Myeloma Working Group (IMWG) criteria.;Progression-Free Survival (PFS): The duration from the date of randomization to either progressive disease per IMWG criteria, or death, whichever occurs first. Timepoint: From randomization up to 12 months. Method of measurement: Response, based on International Myeloma Working Group (IMWG) criteria.;Evaluation of incidence of daratumumab adverse events. Timepoint: During all visits including screening visit; up to one month after the last injection; before, during, and after each intervention (until the next intervention is received). Method of measurement: Assessment of the adverse events reported by th | — |
Countries
Iran (Islamic Republic of)
Contacts
Public ContactDr. Hamidreza Kafi
Orchid Pharmed Co.
Outcome results
None listed