Study Association of Lenalidomide, Ixazomib, Dexamethasone and Daratumumab in Newly Diagnosed Standard Risk Multiple Myeloma

Study Overview
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Brief Summary
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The main objective of this study is to evaluate the minimal residual disease-negativity rate after administration of the combination of Lenalidomide, Ixazomib, Dexamethasone and Daratumumab as induction and consolidation therapy in an intensive program in newly diagnosed standard risk multiple myeloma patients. For the induction therapy, each patient received 6 cycles of Lenalidomide, Ixazomib, Dexamethasone and Daratumumab, then peripheral blood stem cell harvest, intensification with autologous stem cell transplantation, consolidation therapy and maintenance.

Detailed Description
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This is a phase II, multicenter, non-randomized, open-label study to evaluate the safety and efficacy of Lenalidomide, Ixazomib, Dexamethasone, and Daratumumab in patients with newly diagnosed multiple myeloma. The patient population will consist of adult men and women ≤ 65 years, who have a confirmed diagnosis of standard risk multiple myeloma, who meet eligibility criteria. Treatment periods will be defined as 21-day cycles for induction, and 28-day cycles for consolidation, and maintenance. Patients will be seen at regular treatment cycle intervals while they are participating in the study. Patients will be assessed for disease response and progression according to the International Myeloma Working Group criteria at each cycle during induction and consolidation and every other cycle during maintenance. Eastern Cooperative Oncology Group performance status, adverse events, laboratory values, and vital sign measurements will be collected and assessed to evaluate the safety of therapy throughout the study. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events. Patients will attend an End of Treatment visit after receiving their last dose of study drug and will continue to be followed for other follow-up assessments specified in the Schedule of events. All patients will be followed for survival after progression.

Official Title
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Toward a Risk-adapted Strategy to Cure Myeloma : An Intensive Program With Lenalidomide, Ixazomib, and Dexamethasone Plus Daratumumab as Extended Induction and Consolidation Followed by Lenalidomide Maintenance in Newly Diagnosed Standard Risk Multiple Myeloma Patients Eligible for Autologous Stem Cell Transplant : a Phase II Study of the Intergroupe Francophone du Myélome (IFM)

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Ixazomib
* Drug: Lenalidomide
* Drug: Dexamethasone
* Drug: Daratumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: De novo symptomatic myeloma on the International Myeloma Working Group Diagnostic Criteria for the Diagnosis of Multiple Myeloma Measurable disease requiring systemic therapy defined by serum M-component ≥ 10g/l or urine M-component ≥ 200 mg/24h or involved free light level ≥ 100 mg/l Eastern Cooperative Oncology Group performance status 0, 1 or 2 Eligible to high dose therapy Exclusion Criteria: Previously treated with any systemic therapy for multiple myeloma Clinical signs of central nervous system involvement Renal insufficiency defined as estimated Glomerular Filtration Rate lower or equal to 40 ml/min/1.73 m2 Hepatic impairment defined as aspartate transminase or alanine transaminase greater or equal to 3 x upper limit of normal, or Total bilirubin greater or equal to 3 x upper limit of normal Platelet count < 75,000 per µL Absolute neutrophil count ≤ 1,000 cells/mm3 Evidence of current uncontrolled cardiovascular conditions Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening Infection requiring systemic antibiotic therapy or other serious infection within 14 days before first dose of study drug Grade 3 or higher peripheral neuropathy, or grade 2 with pain, on clinical examination during the screening period Known or suspected chronic obstructive pulmonary disease with a Forced Expiratory Volume in 1 second < 50% of predicted normal Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of St. John's wort within 14 days before initiation of the study drug

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: four drugs combination<br>21-day cycles induction, then 28-day cycles consolidation and maintenance with Lenalidomide, Ixazomib, and Dexamethasone Plus Daratumumab | Drug: Ixazomib<br>* 21-day cycles induction and 28-day cycles consolidation<br>Drug: Lenalidomide<br>* 21-day cycles induction and 28-day cycles consolidation and 28-day cycles maintenance therapy<br>Drug: Dexamethasone<br>* 21-day cycles induction and 28-day cycles consolidation<br>Drug: Daratumumab<br>* 21-day cycles induction and 28-day cycles consolidation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| minimal residual disease-negativity rate | after completion of the consolidation therapy and before maintenance | 22 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | up to 54 Months | 
| Response rates | Response rates according to the IMWG criteria after induction, high dose Melphalan, consolidation and maintenance therapy | 3 months, 5 months, 7 months, 13 months, 25 months | 
| Progression free survival |  | 54 months | 
| Overall survival |  | 54 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Newly Diagnosed Multiple myeloma, Daratumumab, Lenalidomide, Ixazomib, Dexamethasone