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

Sponsor

Grupo Cooperativo de Hemopatías Malignas (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04288765

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Daratumumab Only Product in Parenteral Dose Form	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 1, 2020

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Feb 28, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A - Non transplant Carfilzomib Lenalidomide Daratumumab Dexamethasone	Drug: Daratumumab Only Product in Parenteral Dose Form 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 Other Names: Lenalidomide Carfilzomib Dexamethasone
Active Comparator: Group B - transplant Carfilzomib Lenalidomide Daratumumab Dexamethasone Autologous stem cell transplantation (ASCT)	Drug: Daratumumab Only Product in Parenteral Dose Form 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 Other Names: Lenalidomide Carfilzomib Dexamethasone

Arm

Intervention/Treatment

Experimental: Group A - Non transplant

Carfilzomib Lenalidomide Daratumumab Dexamethasone

Drug: Daratumumab Only Product in Parenteral Dose Form

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

Other Names:

Lenalidomide

Carfilzomib

Dexamethasone

Active Comparator: Group B - transplant

Carfilzomib Lenalidomide Daratumumab Dexamethasone Autologous stem cell transplantation (ASCT)

Drug: Daratumumab Only Product in Parenteral Dose Form

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

Other Names:

Lenalidomide

Carfilzomib

Dexamethasone

Outcome Measures

Primary Outcome Measures

Complete response with negative minimal residual disease [10 months]
Complete response with MRD-negative disease measured by inmunophenotype with the International Myeloma Working Group response criteria

Secondary Outcome Measures

Overall survival [36 months]
Overall survival measured on months on both study groups
Progression free survival [36 months]
Progression free survival measured on months from the time to the end of treatment to disease progression on both study groups
Rate of Adverse Events [36 months]
Rate of adverse events rated grade ≥3 by CTCAE 5.0

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.