Safety and Efficacy Study of a Triplet Combination of MLN9708, Lenalidomide and Dexamethasone in the Initial Management of Multiple Myeloma (IFM2013-06)

NCT01936532 | Completed Phase 2

• 2 other identifiers: RC12_04472013-001443-31
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 10

Brief Summary

This is a phase II, multicenter, open-label study to evaluate the safety and efficacy of MLN9708 in combination with Lenalidomide and Dexamethasone in patients with newly diagnosed multiple myeloma. The patient population will consist of adult men and women younger than 66 years, who have a confirmed diagnosis of MM who meet eligibility criteria. Following the screening period, patients will be enrolled and treated then, they will receive induction therapy (3 cycles), a systematic Peripheral Blood Stem Cell harvest. After Peripheral Blood Stem Cell Transplantation, patient will enter in the consolidation phase (early and late one) 2 months after transplantation. Finally, patients follow a Maintenance therapy (start 1 month after the last cycle of consolidation) during 12 months.

Conditions

Newly Diagnosed Multiple Myeloma

Keywords

multiple myeloma

Outcome Measures

Primary Outcomes (1)

• To evaluate the stringent Complete Response (sCR) rate of the combination of MLN9708, Lenalidomide and Dexamethasone in newly diagnosed multiple myeloma (MM) patients after extended consolidation therapy

  sixteen months

Secondary Outcomes (7)

• To evaluate the overall response rate after induction therapy

  after 63 days

• To evaluate the safety Evaluate the safety

  after 63 days

• To evaluate the quality of stem cell harvest

  after 84 days

• To evaluate the overall response rate after high-dose therapy (prior to consolidation)

  after 84 days

• To evaluate the overall response rate after consolidation therapy

  after 270 days

Study Arms (1)

assessment of treatment lenalidomide, dexamethasone,MLN9708

EXPERIMENTAL

Drug: MLN9708; Drug: Lenalidomide; Drug: Dexamethasone

Interventions

MLN9708 DRUG

Induction therapy Patients will receive 3 cycles of induction therapy with MLN9708 (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 of a 28-day cycle. Consolidation therapy * Early consolidation (consolidation part 1) will comprise 2 cycles of MRD identical to induction therapy. * Late consolidation (consolidation part 2) will consist in 6 additional cycles of MLN9708 (4 mg on Days 1, 8 and 15) plus lenalidomide (25 mg on Days 1 through 21) of a 28-day cycle. Maintenance therapy MLN9708 monotherapy (4 mg/day), will be given on days 1, 8 and 15 of a 28 day cycle, during 12 months.

assessment of treatment lenalidomide, dexamethasone,MLN9708

Lenalidomide DRUG

assessment of treatment lenalidomide, dexamethasone,MLN9708

Dexamethasone DRUG

assessment of treatment lenalidomide, dexamethasone,MLN9708

Eligibility Criteria

• Age: 18 Years - 66 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients ≥ 18 years and ≤ 65 years at the time
• Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
• Patients diagnosed with multiple myeloma
• Subjects must have symptomatic myeloma with CRAB criteria.
• Subjects must have measurable disease requiring systemic therapy defined by serum M-component ≥ 5g/l, 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. 7.Subjects must be eligible for high dose therapy.
• Life expectancy ≥ 3 months.9.ECOG performance status 0, 1 or 2. 10.Patients must meet the following clinical laboratory criteria
• Adequate hepatic function, with serum ALT and AST ≤ 3 times the upper limit of normal and serum direct bilirubin ≤ 1.5 times the upper limit of normal within 14 days prior to enrolment.
• 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 (subjects may be receiving red blood cell \[RBC\] transfusions in accordance with institutional guidelines with a wash-out period of 7 days).
• Platelet count ≥ 75 × 109/L (≥ 30 × 109/L if myeloma involvement in the bone marrow is \> 50%) within 14 days prior to enrollment. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days before study enrollment.
• Calculated creatinine clearance ≥ 30 mL/minute (MDRD formula should be used for calculating creatinine clearance values: http://mdrd.com/).
• Female of childbearing potential:must have two negative pregnancy tests : one serum pregnancy test within 10 to 14 days prior to therapy and one urine pregnancy test within 24 hours before starting study drug.
• must agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 3 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
• Male patients, even if surgically sterilized, must agree to not father a child and agree to use a latex condom during therapy and for 3 months after the last dose of study drug, even if they have had a successful vasectomy, if their partner is of childbearing potential.

You may not qualify if:

• Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test within 24 hours before first dose of study drug.
• 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. If the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the MLN9708.
• Treatment by corticosteroids if exceed the equivalent of 160 mg of dexamethasone within 14 days before first dose of study drug.
• Subjects not eligible for high dose therapy.
• Growth factors within 7 days prior to enrolment.
• Transfusion within 3 days prior to enrolment.
• Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to first dose of study drug.
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before first dose of study drug.
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within 6 months.
• Systemic treatment, within 14 days before first dose of study drug, with strong inhibitors of CYP1A2, strong inhibitors of CYP3A or strong CYP3A inducers, or use of Ginkgo biloba or St. John's wort.
• Ongoing or active systemic infection, known human immunodeficiency virus positive, known active hepatitis B virus hepatitis, or known active hepatitis 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

• Nantes University Hospital: lead

Study Sites (10)

CHRU - Hôpital du Haut Lévêque

Bordeaux, 33604, France

Location

CHRU Dijon

Dijon, 21000, France

Location

Centre hospitalier départemental Vendée

La Roche-sur-Yon, 85925, France

Location

CHRU - Hôpital Claude Huriez

Lille, 59037, France

Location

Nantes University Hospital

Nantes, 44093, France

Location

Hôpital Saint-Antoine

Paris, 75 571, France

Location

Centre Hospitalier Lyon sud

Pierre-Bénite, 69495, France

Location

Pole IUC Oncopole CHU

Toulouse, 31059, France

Location

CHRU - Hôpital Bretonneau

Tours, 37044, France

Location

CHRU - Hôpitaux de Brabois

Vandœuvre-lès-Nancy, 54511, 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

• Philippe MOREAU

  Nantes University Hospital

  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 29, 2013
• First Posted: September 6, 2013
• Study Start: November 12, 2014
• Primary Completion: March 1, 2019
• Study Completion: June 4, 2020
• Last Updated: August 3, 2023

Record last verified: 2023-08

Locations

FR (10)