Carfilzomib, Daratumumab, Lenalidomide and Dexamethasone as First Line Treatment in Multiple Myeloma

Study Overview
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Brief Summary
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Carfilzomib in combination with lenalidomide, daratumumab and dexamethasone (KRDd) can induce profound clinical responses. The investigators want to observe the effectiveness of the quadruple therapy of carfilzomib, lenalidomide, daratumumab and dexamethasone on patients receiving 8 cycles of KRDd with autologous stem cell transplantation versus patients with 8 cycles of KRDd without autologous stem cell transplantation.

Official Title
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Carfilzomib, Daratumumab, Lenalidomide and Dexamethasone as First Line Treatment in Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Daratumumab Only Product in Parenteral Dose Form


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with newly diagnosed and previously untreated multiple myeloma by the International Myeloma Working Group criteria that requires treatment based on: Presence of elevated calcium, renal failure, anemia and/or bone lesions (CRAB) Clonal bone marrow plasma cells ³ 60% Involved/uninvolved serum free light chain ratio ³ 100 >1 focal lesions on MRI studies (³5 mm in size) Age > 18 years Functional stage of 0 - 1 measured by the Eastern Cooperative Oncology Group (ECOG) scale. Capacity and willingness to provide a written informed consent. Exclusion Criteria: POEMS syndrome Systemic amyloidosis Plasma cells leukemia Radiotherapy on multiple sites on the period of 4 weeks before the initiation of treatment (1 week if it is one region) Improper liver function: total bilirubin > 1.5 x upper limit of normal (ULN) or > 3 x ULN in patients with Gilbert syndrome, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 3.0 x ULN. Non-controlled systematic active infection (viral, bacterial and/or fungic). Patients with known infection by human immunodeficiency virus (HIV). Active infection by hepatitis B. Active infection by hepatitis C. Significant cardiovascular diseases as uncontrolled or symptomatic arrhythmias, congestive heart failure or acute myocardial infarction within 2 months prior to screening, or any New York Heart Association (NYHA) class 3 or 4 heart disease. Diagnosis of previous malignancies for 2 years, with exception of patients with basal or squamous cell carcinoma or in situ carcinoma of cervix or breast. History of allergic reaction or severe anaphylaxis to humanized or murine monoclonal antibodies. Pregnant or lactating women.

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients with newly diagnosed and previously untreated multiple myeloma living in Mexico that are fit for a quadruple therapy for multiple myeloma. Those patients that aren't fit or unavailable for transplant will go to the continuous treatment arm. The stratification of the study will be done by age and by cytogenetic risk.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A - Non transplant<br>Carfilzomib Lenalidomide Daratumumab Dexamethasone | Drug: Daratumumab Only Product in Parenteral Dose Form<br>* Induction = 8 cycles Carfilzomib on Day 1st, 8th and 15th Lenalidomide: Day 1 to 21 Daratumumab: Cycles 1-2: weekly Cycles 3-4: every two weeks Cycles 5-8: every month Dexamethasone: 40 mg weekly<br>* Other names: Dexamethasone;|
| Active Comparator: Group B - transplant<br>Carfilzomib Lenalidomide Daratumumab Dexamethasone Autologous stem cell transplantation (ASCT) | Drug: Daratumumab Only Product in Parenteral Dose Form<br>* Induction = 8 cycles Carfilzomib on Day 1st, 8th and 15th Lenalidomide: Day 1 to 21 Daratumumab: Cycles 1-2: weekly Cycles 3-4: every two weeks Cycles 5-8: every month Dexamethasone: 40 mg weekly<br>* Other names: Dexamethasone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response with negative minimal residual disease | Complete response with MRD-negative disease measured by inmunophenotype with the International Myeloma Working Group response criteria | 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival measured on months on both study groups | 36 months | 
| Progression free survival | Progression free survival measured on months from the time to the end of treatment to disease progression on both study groups | 36 months | 
| Rate of Adverse Events | Rate of adverse events rated grade ≥3 by CTCAE 5.0 | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Newly diagnosed