Health Condition 1: C00-D49- Neoplasms
Conditions
Interventions
Intervention1: Intas daratumumab (INTP33) Injection, for intravenous use: Dose: Each 5 mL vial contains 100 mg of daratumumab (20 mg daratumumab per mL). Each 20 mL vial contains 400 mg of daratumumab
Sponsors
Intas Pharmaceuticals Limited
Intas Pharmaceuticals Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1) 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. 2) Male and Female participants must be greater than or equal to 18 years (completed) when signing the informed consent. 3) Participants must have documented diagnosis of multiple myeloma as defined by International Myeloma Working Group updated criteria (Appendix 9). 4) 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. 5) 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 s
Exclusion criteria
Exclusion criteria: 1) 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. 2) Contraindications to the use of lenalidomide and dexamethasone per local prescribing information. 3) 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 Waldenstr m 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. 4) 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. 5) 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. 6) 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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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-ineligible participants with newly diagnosed multiple myelomaTimepoint: 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 | — |
Secondary
| Measure | Time frame |
|---|---|
| To establish the anti-tumour activity of Intas daratumumab (INTP33), lenalidomide and dexamethasone against DARZALEX, lenalidomide and dexamethasone in transplant-ineligible participants with newly diagnosed multiple myeloma To establish the anti-tumour activity of Intas daratumumab (INTP33), lenalidomide and dexamethasone against DARZALEX, lenalidomide and dexamethasone in transplant-ineligible participants with newly diagnosed multiple myeloma To compare pharmacokinetic parameters after 1st dose of Intas daratumumab with DARZALEX, both given in combination with lenalidomide and dexamethasone in transplant-ineligible participants with newly diagnosed multiple myeloma To compare trough blood levels during the treatment cycles in transplant-ineligible participants with newly diagnosed multiple myelomaTimepoint: 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 | — |
Countries
India
Contacts
Public ContactDr Jogesh Mahajan
Lambda Therapeutic Research Ltd
Outcome results
None listed