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

Multiple Myeloma Clinical Trial

— IFM2018-01  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03669445
• Other study ID #: RC31/18/0212
• Status: Recruiting
• Phase: Phase 2
• Start date: December 31, 2018
• Est. completion date: December 2024

Study information

• Verified date: July 2020
• Source: University Hospital, Toulouse
• Contact: Laura BOGDANOVITCH, CRA
• Phone: 05 61 77 84 37
• Email: laura.bogdanovitch[@]chu-toulouse.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: December 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Ixazomib
21-day cycles induction and 28-day cycles consolidation
• Lenalidomide
21-day cycles induction and 28-day cycles consolidation and 28-day cycles maintenance therapy
• Dexamethasone
21-day cycles induction and 28-day cycles consolidation
• Daratumumab
21-day cycles induction and 28-day cycles consolidation

Locations

Country	Name	City	State
France	CHU Bordeaux	Bordeaux
France	CHU de Caen	Caen
France	CHU de Dijon	Dijon
France	CHU de Grenoble	Grenoble
France	CHRU de Lille	Lille
France	Hospices Civils de Lyon	Lyon
France	Institut Paoli Calmettes	Marseille
France	CHRU de Nancy	Nancy
France	CHU de Nantes	Nantes
France	CHU de Rennes	Rennes
France	University Hosptial Toulouse	Toulouse
France	CHU de Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	minimal residual disease-negativity rate	after completion of the consolidation therapy and before maintenance	22 months
Secondary	Adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	up to 54 Months
Secondary	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
Secondary	Progression free survival		54 months
Secondary	Overall survival		54 months