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IRCT20150303021315N38 IRCT 2025-10-28 CinnaGen Company A comparison of the efficacy and safety of daratumumab (produced by CinnaGen Co.) versus the reference daratumumab (Darzalex®, produced by Janssen Biotech, Inc.) in relapsed or refractory multiple myeloma patients A phase III, randomized, parallel, two-arm, double-blind, multi-center, active-controlled, non-inferiority clinical trial to compare efficacy and safety of daratumumab (produced by CinnaGen Co.) versus the reference daratumumab (Darzalex®, produced by Janssen Biotech, Inc.) in relapsed or refractory multiple myeloma patients 2025-11-22 anticipated 128 Recruiting https://irct.ir/trial/86533 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment, Randomization description: Randomization of patients will be conducted using Stata software (v. MP 18, StataCorp, US.), utilizing block randomization (with size 2 and 4) stratified by disease stage (I, II or III) and number of prior lines of therapy (1 or 2) for a total of 128 patients (with a 1:1 ratio). Prior to the start of the study, the generated randomization series, along with the seed used for generating random numbers. The randomization process will be performed centrally, meaning that each patient will be allocated to one of these strata upon entering the study based on their conditions. Then, by contacting the unit responsible for randomization, they will be assigned to a treatment group using the random list corresponding to that stratum. Each randomized patient will be assigned a unique identification code for the duration of the study. The assigned code will consist of four letters (the first two letters of the first name and the first two letters of the last name), three numbers (the center code), three letters representing the generic drug name (which is DRT), and three digits (corresponding to the randomization code), forming the patient code. For example: ABCD001 DRT-001. The randomization numbers will be assigned sequentially, Blinding description: Both vials of daratumumab (manufactured by SinaGen Research and Production Company) and Darzalex® (manufactured by Janssen Biotech, Inc.) used in the study were indistinguishable to patients and study staff, as they were completely identical in shape, size, material, and color, and therefore the brand of the drug could not be identified by appearance. The drug containers of daratumumab (manufactured by SinaGen Research and Production Company) and Darzalex® (manufactured by Janssen Biotech, Inc.) were also placed in identical packaging, making them visually indistinguishable. Randomization will not be disclosed to the study investigators. Individuals responsible for data review and analysis will remain blinded to patient group allocation. 3 Relapsed or Refractory Multiple Myeloma. 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 beyond) - Lenalidomide 25 mg orally once daily, on days 1-21 of each 28-day cycle- Dexamethasone 40 mg orally once weekly. Intervention 2: Control group:- Daratumumab (Darzalex®, manufactured by Janssen Biotech, Inc.) 16 mg/kg intravenous infusion once weekly (cycles 1-2), every two weeks (cycles 3-6), and every four weeks (cycles 7 and beyond) - Lenalidomide 25 mg orally once daily, on days 1-21 of each 28-day cycle- Dexamethasone 40 mg orally once weekly. Undecided - It is not yet known if there will be a plan to make this available Justification or reason for indecision in sharing IPD is It will be decided in the future
public Dr. Hamidreza Kafi
No 42, Attar St., Vanak Sq, Tehran, Iran
Tehran Iran (Islamic Republic of) 1994766411 +98 21 4347 3000 Kafi.H@orchidpharmed.com Orchid Pharmed Co. scientific Dr. Sahar Tavakoli Shiraji
Shariati Educational, Research, and Clinical Center, Jalal-Al-Ahmad Junction, North Kargar Street, Tehran
Tehran Iran (Islamic Republic of) 1411713135 +98 21 8490 1000 sahar.ts78@yahoo.com Tehran University of Medical Sciences Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) 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 18 years no limit Both 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 fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study or within 2 weeks after the last dose of study treatment. Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate. Kyphoplasty or vertebroplasty are not considered major surgery. Has had a plasmapheresis within 28 days before randomization Radiation therapy (with the exception of palliative radiation therapy) within 14 days before randomization Subject has any concurrent medical condition or disease (eg, active systemic infection) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study C90.0 Multiple myeloma Treatment - Drugs Treatment - Drugs 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 beyond) - Lenalidomide 25 mg orally once daily, on days 1-21 of each 28-day cycle- Dexamethasone 40 mg orally once weekly Control group:- Daratumumab (Darzalex®, manufactured by Janssen Biotech, Inc.) 16 mg/kg intravenous infusion once weekly (cycles 1-2), every two weeks (cycles 3-6), and every four weeks (cycles 7 and beyond) - Lenalidomide 25 mg orally once daily, on days 1-21 of each 28-day cycle- Dexamethasone 40 mg orally once weekly 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. 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 the patient or physician, and evaluation of severity, seriousness and causal relationship of adverse events with daratumumab based on international guidelines, such as the guidelines of the World Health Organization. Assessment of anti-daratumumab antibody development in patients. Timepoint: At screening visit and weeks 24 and 52 after inititation of treatment with daratumumab. Method of measurement: Blood sampling for the evaluation of anti-daratumumab antibody serum using ELISA method. CinnaGen Company Approved 2025-10-01 Dr. Shariati Educational, Research and Clinical Center Ethics Committee, TUMS Dr. Shariati Educational, Research and Clinical Center, Opposite to Faculty of Economics, Jalal Al Ahmad Crossroad, North Kargar Street, Tehran, Iran Tehran Tehran Iran (Islamic Republic of)