Clinical trial NCT03669445: Study Association of Lenalidomide, Ixazomib, Dexamethasone and Daratumumab in Newly Diagnosed Standard Risk Multiple Myeloma
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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Newly Diagnosed Multiple myeloma
Daratumumab
Lenalidomide
Ixazomib
Dexamethasone
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2018-09-13
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: minimal residual disease-negativity rate
timeFrame: 22 months
Secondary outcomes:
measure: Adverse events
timeFrame: up to 54 Months
measure: Response rates
timeFrame: 3 months, 5 months, 7 months, 13 months, 25 months
measure: Progression free survival
timeFrame: 54 months
measure: Overall survival
timeFrame: 54 months
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Caen
country: France
facility: CHU de Caen
city: Dijon
country: France
facility: CHU de Dijon
city: Grenoble
country: France
facility: CHU de Grenoble
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Nancy
country: France
facility: CHRU de Nancy
city: Nantes
country: France
facility: CHU de Nantes
city: Rennes
country: France
facility: CHU de Rennes
city: Toulouse
country: France
facility: University Hosptial Toulouse
city: Tours
country: France
facility: CHU de Tours
Study officials:
affiliation: University Hospital, Toulouse
name: Michel ATTAL, MD
role: STUDY_DIRECTOR
References: