Study Association of Lenalidomide, Ixazomib, Dexamethasone and Daratumumab in Newly Diagnosed Standard Risk Multiple Myeloma (IFM2018-01)
Primary Purpose
Multiple Myeloma
Status
Recruiting
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Ixazomib
Lenalidomide
Dexamethasone
Daratumumab
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Newly Diagnosed Multiple myeloma, Daratumumab, Lenalidomide, Ixazomib, Dexamethasone
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
Sites / Locations
- CHU Bordeaux
- CHU de Caen
- CHU de Dijon
- CHU de Grenoble
- CHRU de Lille
- Hospices Civils de Lyon
- Institut Paoli Calmettes
- CHRU de Nancy
- CHU de Nantes
- CHU de Rennes
- University Hosptial ToulouseRecruiting
- CHU de Tours
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
four drugs combination
Arm Description
21-day cycles induction, then 28-day cycles consolidation and maintenance with Lenalidomide, Ixazomib, and Dexamethasone Plus Daratumumab
Outcomes
Primary Outcome Measures
minimal residual disease-negativity rate
after completion of the consolidation therapy and before maintenance
Secondary Outcome Measures
Adverse events
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Response rates
Response rates according to the IMWG criteria after induction, high dose Melphalan, consolidation and maintenance therapy
Progression free survival
Overall survival
Full Information
NCT ID
NCT03669445
First Posted
September 11, 2018
Last Updated
July 29, 2020
Sponsor
University Hospital, Toulouse
1. Study Identification
Unique Protocol Identification Number
NCT03669445
Brief Title
Study Association of Lenalidomide, Ixazomib, Dexamethasone and Daratumumab in Newly Diagnosed Standard Risk Multiple Myeloma
Acronym
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)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Recruiting
Study Start Date
December 31, 2018 (Actual)
Primary Completion Date
March 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Newly Diagnosed Multiple myeloma, Daratumumab, Lenalidomide, Ixazomib, Dexamethasone
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
four drugs combination
Arm Type
Experimental
Arm Description
21-day cycles induction, then 28-day cycles consolidation and maintenance with Lenalidomide, Ixazomib, and Dexamethasone Plus Daratumumab
Intervention Type
Drug
Intervention Name(s)
Ixazomib
Intervention Description
21-day cycles induction and 28-day cycles consolidation
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Intervention Description
21-day cycles induction and 28-day cycles consolidation and 28-day cycles maintenance therapy
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
21-day cycles induction and 28-day cycles consolidation
Intervention Type
Drug
Intervention Name(s)
Daratumumab
Intervention Description
21-day cycles induction and 28-day cycles consolidation
Primary Outcome Measure Information:
Title
minimal residual disease-negativity rate
Description
after completion of the consolidation therapy and before maintenance
Time Frame
22 months
Secondary Outcome Measure Information:
Title
Adverse events
Description
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame
up to 54 Months
Title
Response rates
Description
Response rates according to the IMWG criteria after induction, high dose Melphalan, consolidation and maintenance therapy
Time Frame
3 months, 5 months, 7 months, 13 months, 25 months
Title
Progression free survival
Time Frame
54 months
Title
Overall survival
Time Frame
54 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Laura BOGDANOVITCH, CRA
Phone
05 61 77 84 37
Ext
+33
Email
laura.bogdanovitch@chu-toulouse.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michel ATTAL, MD
Organizational Affiliation
University Hospital, Toulouse
Official's Role
Study Director
Facility Information:
Facility Name
CHU Bordeaux
City
Bordeaux
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cyrille HULIN
Facility Name
CHU de Caen
City
Caen
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Margaret MACRO
Facility Name
CHU de Dijon
City
Dijon
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Denis CAILLOT
Facility Name
CHU de Grenoble
City
Grenoble
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clara MARIETTE
Facility Name
CHRU de Lille
City
Lille
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thierry FACON
Facility Name
Hospices Civils de Lyon
City
Lyon
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lionel KARLIN
Facility Name
Institut Paoli Calmettes
City
Marseille
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Anne-Marie STOPPA
Facility Name
CHRU de Nancy
City
Nancy
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aurore PERROT
Facility Name
CHU de Nantes
City
Nantes
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philippe MOREAU
Facility Name
CHU de Rennes
City
Rennes
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martine ESCOFFRE
Facility Name
University Hosptial Toulouse
City
Toulouse
ZIP/Postal Code
31000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michel Attal, MD PhD
Facility Name
CHU de Tours
City
Tours
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lotfi BENBOUBKER
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Study Association of Lenalidomide, Ixazomib, Dexamethasone and Daratumumab in Newly Diagnosed Standard Risk Multiple Myeloma
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