临床试验/CTRI/2025/08/092681

CTRI/2025/08/092681尚未招募3 期

A Prospective, Randomized, Double-Blind, Active-Controlled, Multi-Centre, Two-Arm, Phase-I/III Study to Investigate Safety, Efficacy, Pharmacokinetics and Immunogenicity of Intas Daratumumab (INTP33) Compared of DARZALEX® in Transplant-Ineligible Participants with Newly Diagnosed Multiple Myeloma

Intas Pharmaceuticals Limited31 个研究点分布在 1 个国家目标入组 238 人开始时间: 2025年8月18日最近更新: 2026年4月1日

试验速览

阶段: 3 期
状态: 尚未招募
发起方: Intas Pharmaceuticals Limited
入组人数: 238
试验地点: 31
主要终点: To establish the non-inferiority of Intas

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

To establish the non-inferiority of Intas daratumumab (INTP33), lenalidomide and dexamethasone against DARZALEX, lenalidomide and dexamethasone in terms of overall response rate (ORR) in transplant

研究设计

研究类型: Interventional
分配方式: Randomized
盲法: Double

入排标准

年龄范围: 18.00 Year(s) 至 60.00 Year(s)（—）
性别: All

入选标准

•Must sign an ICF indicating that the participant understands the purpose of and procedures required for the study as described in section 10.1.3 and in this protocol and is willing to participate in the study.
•Male and Female participants must be greater than or equal to 18 years (completed) when signing the informed consent.
•Participants must have documented diagnosis of multiple myeloma as defined by International Myeloma Working Group updated criteria (Appendix 9).
•Evidence of measurable disease, as assessed by local laboratory, defined by any of the following: Serum monoclonal paraprotein (M-protein) level greater than or equal to 1.0 g per dL measured using serum protein immunoelectrophoresis (sPEP) OR urine M-protein level reater than or equal to 200 mg per 24 hours measured using urine protein immunoelectrophoresis (uPEP) AND OR Serum free light chain multiple myeloma without measurable disease in serum or urine as per previous criteria: Serum Ig involved free light chain greater than or equal to 10 mg per dL and abnormal serum Ig kappa to lambda free light chain ratio.
•Be newly diagnosed and not considered candidate for high-dose chemotherapy with ASCT as per investigator’s assessment due to any of the following: Ineligible due to advanced age; OR Ineligible due to the presence of important comorbid condition(s) likely to have impact on tolerability of high dose chemotherapy with ASCT; OR Deferral of high-dose chemotherapy with ASCT as initial treatment for any other reasons 6) Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 (Refer to Appendix 5) 7) Participants must have screening clinical laboratory values meeting the following criteria: a) Haemoglobin greater than or equal to 7.5 g per dL (prior transfusion support or ESA is permitted but must be without transfusion support or ESA use within 7 days before the screening laboratory assessment) b) Absolute neutrophil count (ANC) greater than or equal to 1.0 into 109 per L (prior growth factor support is permitted but must be without support within 7 days for G-CSF or GM-CSF and 14 days for pegylated-GCSF of the screening laboratory assessment) c) Platelet count greater than or equal to 70,000 per uL if less than 50 percentage of BM nucleated cells are plasma cells, or greater than or equal to 50,000 per uL if greater than or equal to 50 percentage of BM nucleated cells are plasma cells (without transfusion support or thrombopoietin receptor agonist within 3 days of the screening laboratory assessment) d) Aspartate aminotransferase (AST) less than or equal to 2.5 into upper limit of normal (ULN) e) Alanine aminotransferase (ALT) less than or equal to 2.5 into ULN f) Total bilirubin less than or equal to 2 into ULN, except in participants with congenital bilirubinaemia, such as Gilbert syndrome (in which case direct bilirubin less than or equal to 2.0 into ULN is required).
•g) Creatinine clearance greater than 30 mL per min based on Cockcroft-Gault (Refer to Appendix 6 for details).
•h) Potassium level greater than or equal to 3.0 mEq per L i) Corrected serum calcium less than 14 mg per dL (less than 3.5 mmol per L); or free ionized calcium less than 6.5 mg per dL (less than 1.6 mmol per L) (Appendix 7) 8) A female participant is eligible to participate if she is not pregnant or breastfeeding and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) as defined in Appendix 4 OR Is a WOCBP and agrees to remain on an acceptable contraceptive method that is highly effective (with a failure rate of less than 1 percentage per year), preferably with low user dependency when used consistently and correctly, as described in Appendix 4 during the intervention period and for at least 03 months after the last dose of the study intervention.
•The investigator should evaluate the effectiveness and the potential for contraceptive method failure (e.g., noncompliance, recently initiated) of the contraceptive method in relation to the first dose of the study intervention.
•A WOCBP agrees not to donate eggs (ova, oocytes), freeze them for future use for reproduction or retrieve them for their use during the recommended period of contraception.
•A WOCBP must have a negative highly sensitive pregnancy test serum as required by local regulations within at screening and urine pregnancy test on day 1 randomization, before the first dose of the study intervention.
•In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
•Additional requirements for pregnancy testing during and after study intervention are located in section 8.3.
•The investigator is responsible for reviewing medical history, menstrual history, and recent sexual activity to decrease the risk of inclusion of a woman with early undetected pregnancy.
•Contraceptive use by participants or participant’s partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
•Male participants are eligible to participate if they agree to the following during the intervention period and for at least 04 months after the last dose of study intervention: Must agree not to plan to father a child or donate sperm for reproduction.
•OR Must agree to use contraception barrier as detailed below a male participant must wear a condom when engaging in any activity that allows for the passage of ejaculate to another person with female partner use of an additional highly effective contraceptive method with a failure rate of less than 1 percentage per year as described in Appendix 4 10) Willing and able to adhere to the lifestyle restrictions specified in this protocol.

排除标准

•Known allergies, hypersensitivity, or intolerance to any of the study interventions (daratumumab, lenalidomide and dexamethasone) or components excipients thereof (refer to the IB of daratumumab and local prescribing information documents of DARZALEX, lenalidomide and dexamethasone), or drug or other allergies to monoclonal antibodies or human proteins, or known sensitivity to mammalian-derived products, that in the opinion of the investigator or medical monitor, contraindicate participation in the study.
•Contraindications to the use of lenalidomide and dexamethasone per local prescribing information.
•Diagnosis of plasma cell leukaemia at the time of screening; systemic light chain amyloidosis; POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes); or Waldenström’s disease or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
•Any treated plasma cell dyscrasia [e.g., multiple myeloma, smoldering multiple myeloma (SMM), monoclonal gammopathy of undefined significance (MGUS)] with following exceptions: a short course of corticosteroids (not to exceed 40 mg of dexamethasone, or equivalent per day for a maximum of 4 days, total of 160 mg dexamethasone or equivalent).
•In addition, received a cumulative dose of systemic corticosteroids equivalent to greater than or equal to 20 mg of dexamethasone during the Screening Phase.
•Prior or current systemic therapy or stem cell transplant (SCT) for MM, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg per day for a maximum 4 days) of corticosteroids before treatment.
•Participants will be excluded if they have any of the following: Any history of malignancy in the last 3 years prior to randomization, other than multiple myeloma, SMM and MGUS which is considered at high risk of recurrence requiring systemic therapy OR Any active malignancy (i.e., progressing or requiring treatment change) in the last 3 years prior to randomization other multiple myeloma, SMM and MGUS.
•The only allowed exceptions are malignancies treated within the last 3years that are considered cured: Non-muscle invasive bladder cancer Nonmelanoma skin cancer or lentigo maligna who underwent adequate treatment with no active disease at present Non-invasive cervical cancer Breast cancer: Adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence Adequately treated carcinoma in situ Localized non-invasive primary disease under surveillance Localized prostate cancer (Any T, N0M0): Very-low, low or intermediate risk group, treated (radical prostatectomy/radiation therapy focal treatment; with or without ADT) or untreated and under either observation or active surveillance; OR High or very-high risk group who have completed the treatment with curative intent (including adjuvant ADT) more than 6 months prior to full study screening and considered to have a very low risk of recurrence; Other malignancy that is considered cured with minimal risk of recurrence with low potential risk for risk of metastasis or death (e.g., 5-year OS rate greater than 90 percentage) in consultation with the sponsor’s medical monitor 7) Received focal radiation therapy within 14 days of randomization.
•Radiotherapy within 14 days on measurable soft-tissue plasmacytoma(s) is not permitted even in the setting of palliation for symptomatic management.
•Any major procedure within 14 days before the initiation of the study treatment: plasmapheresis, major surgery (kyphoplasty is not considered a major procedure).
•Clinical signs of CNS or meningeal involvement of multiple myeloma.
•If either is suspected, negative brain and total spine MRI (with and without contrast) and cerebral spinal fluid cytology are required.
•Has moderate or severe persistent asthma within the past 2 years OR uncontrolled asthma of any classification (Participants who have controlled intermittent asthma or control mild persistent asthma are allowed in the study).
•Has COPD with an FEV1 less than 50 percentage of predicted (FEV1 testing is required only for participants suspected of having COPD).
•Presence of hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) total immunoglobulin (Ig) or IgG at screening or within 3 months prior to the first dose of investigational intervention.
•Positive hepatitis C antibody test result at screening or within 3 months prior to starting the investigational intervention.
•NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C RNA test is obtained.
•Has known human immunodeficiency virus (HIV) seropositive status or positive HIV antibody test at screening.
•For participants with unknown HIV status, HIV testing will be performed at screening unless prohibited by local regulations.
•Participant with clinically significant current or recent (within the past 6 months before randomization [unless otherwise specified below]) cardiac conditions as defined below: a) Acute coronary syndrome, stroke (including transient ischemic attack [TIA]) or other ischemic event or thromboembolic event (e.g., deep vein thrombosis [DVT], pulmonary embolism) b) Clinical risk assessment of cardiac function using the New York Heart Association Functional Classification of Class III or greater c) Clinically significant cardiac arrhythmia (serious cardiac arrhythmia not controlled by adequate medication, severe conduction abnormality) as per investigator assessment d) Electrocardiographic evidence of clinically significant acute ischemic or active conduction system abnormalities which is medically relevant and affect safety as per investigator assessment.
•e) Any other cardiac illness that could lead to a safety risk to the participant f) Participants with a known left ventricular ejection fraction (LVEF) less than 40 percentage at the screening assessment.
•Note: Participants with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF less than 50 percentage must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist, if appropriate.
•Participants are not expected to comply with the requirement of the protocol as per the investigator assessment (alcoholics, drug addicts, psychiatric patients, or medical condition).
•Participant as per investigator is not medically fit or have a situation which can affect safety or efficacy assessment.
•Had major surgery within 2 weeks before randomization or has not fully recovered from surgery as per investigators assessment.
•Contraindications to prophylaxis for deep vein thrombosis and pulmonary embolism.
•Past or intended use of any disallowed therapies as noted in section 6.9, Prior and Concomitant Therapy within 30 days prior to the first dose of the study intervention.
•Presence of gastrointestinal disease that can affect absorption of drugs.
•Woman who is pregnant, or breastfeeding, or planning pregnancy during study.
•OR, Man wanting to father a child during study.
•Received any other investigational intervention or used an invasive investigational medical device within 04 weeks or 5 half-lives prior to the first dose of study intervention, whichever is longer.
•24 Documented medical history of uncontrolled, clinically significant intercurrent medical condition(s) for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

结局指标

主要结局

To establish the non-inferiority of Intas

时间窗: 0.000 (Pre-dose), 0.500, 1.000 and 3.000 hours after start of infusion, End of infusion, 0.500, 1.000, 2.000, 3.000, 5.000 hours after completion of infusion, 24.000, 48.000 hours after start of infusion, 120.000, 144.000 hours after start of infusion, 168.000 hours after start of infusion

daratumumab (INTP33), lenalidomide and

dexamethasone against DARZALEX, lenalidomide and dexamethasone in terms of overall response rate (ORR) in transplant-ineligible participants with newly diagnosed

multiple myeloma

次要结局

To establish the anti-tumour activity of Intas(daratumumab (INTP33), lenalidomide and)

研究者

发起方

Intas Pharmaceuticals Limited

申办方类型

Pharmaceutical industry-Indian

责任方

Principal Investigator

主要研究者

Dr Naman Shah

Lambda Therapeutic Research Ltd

研究点 (31)

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