Ixazomib, Lenalidomide, Dexamethasone Induction and Extended Consolidation Plus Lenalidomide Maintenance in Multiple Myeloma

NCT02897830 | Terminated Phase 2

• 1 other identifier: 14 7261 03
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Open-label study to evaluate the safety and efficacy of Ixazomib in combination with Lenalidomide and Dexamethasone in patients with newly diagnosed multiple myeloma (MM). The patient population will consist of adult men and women up to 65 years, who have a confirmed diagnosis of MM who meet eligibility criteria.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• rate of stringent complete response

  after consolidation and before maintenance therapy

  13 months

Secondary Outcomes (7)

• Adverse events

  up 60 Months

• response rates

  3 months, 5 months, 7 months, 13 months, 25 months

• Progression free survival

  60 months

• overall survival

  60 months

• Percentage of patients for whom more than 5X106 CD34 cells will be collected.

  3 months

Study Arms (1)

Study treatment

EXPERIMENTAL

Ixazomib, Lenalidomide, Dexamethasone Induction and extended Consolidation followed by Lenalidomide Maintenance

Drug: Ixazomib; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Ixazomib DRUG

induction therapy: comprising three 28-day cycles with Ixazomib (4 mg) on Days 1, 8 and 15 plus Lenalidomide (25 mg) on Days 1 through 21 and Dexamethasone (40 mg) on Days 1, 8, 15 and 22. Early consolidation : (consolidation part 1) will start 2 months (-/+ 14 days) after transplantation and will comprise 2 cycles of MLN - Rd (MLN R identical to induction therapy but low dose of Dexamethasone 20mg/d once a week). Late consolidation (consolidation part 2) will consist in 6 additional 28-day cycles of Ixazomib (4 mg on Days 1, 8 and 15) plus Lenalidomide (25 mg on Days 1 through 21).

Also known as: MLN 9708

Study treatment

Lenalidomide DRUG

induction therapy: comprising three 28-day cycles with Ixazomib (4 mg) on Days 1, 8 and 15 plus Lenalidomide (25 mg) on Days 1 through 21 and Dexamethasone (40 mg) on Days 1, 8, 15 and 22. Early consolidation : (consolidation part 1) will start 2 months (-/+ 14 days) after transplantation and will comprise 2 cycles of MLN - Rd (MLN R identical to induction therapy but low dose of Dexamethasone 20mg/d once a week). Late consolidation (consolidation part 2) will consist in 6 additional 28-day cycles of Ixazomib (4 mg on Days 1, 8 and 15) plus Lenalidomide (25 mg on Days 1 through 21). Maintenance therapy will start within 28 days after the last dose of Lenalidomide in last cycle of Late Consolidation: Lenalidomide 10 mg/d taken on Days 1 through 21 for thirteen 28-day cycles

Also known as: Revlimid

Study treatment

Dexamethasone DRUG

induction therapy: comprising three 28-day cycles with Ixazomib (4 mg) on Days 1, 8 and 15 plus Lenalidomide (25 mg) on Days 1 through 21 and Dexamethasone (40 mg) on Days 1, 8, 15 and 22. Early consolidation : (consolidation part 1) will start 2 months (-/+ 14 days) after transplantation and will comprise 2 cycles of MLN - Rd (MLN R identical to induction therapy but low dose of Dexamethasone 20mg/d once a week).

Study treatment

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Multiple myeloma based on the new IMWG Diagnostic Criteria for plasma cells disorders
• Symptomatic myeloma with CRAB criteria
• Measurable disease requiring systemic therapy defined by serum M-component ≥ 5g/l or urine M-component ≥ 200 mg/24h or serum FLC ≥ 100 mg/l.
• Subjects must not have been treated previously with any systemic therapy for multiple myeloma.
• Eligibility for high dose therapy.
• Life expectancy ≥ 3 months
• ECOG performance status 0, 1 or 2
• Patients must meet the following clinical laboratory criteria:
• Adequate hepatic function,
• Absolute neutrophil count (ANC) ≥ 1.0 × 109/L within 14 days prior to enrollment.
• Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to enrollment
• Platelet count ≥ 75 × 109/L eRenal eGFR ≥ 50 mL/minute within 7 days

You may not qualify if:

• Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening
• Evidence of mucosal or internal bleeding and/or platelet refractory.
• Prior myeloma systemic therapy
• Major surgery within 14 days before first dose of study drug.
• Radiotherapy within 14 days before first dose of study drug.
• Corticosteroids if exceed the equivalent of 160 mg of dexamethasone within 14 days before first dose of study drug
• Central nervous system involvement
• Growth factors within 7 days of screening
• Transfusion within 7 days of screening
• Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to first dose of study drug
• Infection .
• Evidence of current uncontrolled cardiovascular conditions,
• Systemic treatment, within 14 days before first dose of study drug, with strong inhibitors of CYP1A2 , strong inhibitors of CYP3A or use of Ginkgo biloba or St. John's wort.
• Ongoing or active systemic infection, known human immunodeficiency virus (HIV) positive, known active hepatitis B virus hepatitis, or known active hepatitis C virus hepatitis and history of hepatitis B or C virus hepatitis.
• \. Co-morbid systemic illnesses or other severe concurrent disease that, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.

Sponsors & Collaborators

• University Hospital, Toulouse: lead
• Takeda: collaborator
• Celgene: collaborator

Study Sites (1)

University Hosptial Toulouse

Toulouse, 31000, France

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

ixazomib; Lenalidomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Michel ATTAL, MD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

• Murielle ROUSSEL, MD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2015
• First Posted: September 13, 2016
• Study Start: August 5, 2016
• Primary Completion: November 1, 2018
• Study Completion: August 31, 2020
• Last Updated: November 12, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)