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

Phase 2

Completed

• Conditions: Newly Diagnosed Multiple Myeloma
• Interventions: Drug: MLN9708; Drug: Lenalidomide; Drug: Dexamethasone

• Registration Number: NCT01936532
• Lead Sponsor: Nantes University Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-07-29
• Study First Submitted QC: 2013-09-03
• Study First Posted: 2013-09-06
• Study Start: 2014-11-12
• Primary Completion: 2019-03
• Study Completion: 2020-06-04
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-02
• Last Update Posted: 2023-08-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

Not provided

Exclusion Criteria

1. 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.
2. Evidence of mucosal or internal bleeding and/or platelet refractory.
3. Prior myeloma systemic therapy.
4. Major surgery within 14 days before first dose of study drug.
5. 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.
6. Treatment by corticosteroids if exceed the equivalent of 160 mg of dexamethasone within 14 days before first dose of study drug.
7. Subjects not eligible for high dose therapy.
8. Growth factors within 7 days prior to enrolment.
9. Transfusion within 3 days prior to enrolment.
10. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to first dose of study drug.
11. Infection requiring systemic antibiotic therapy or other serious infection within 14 days before first dose of study drug.
12. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within 6 months.
13. 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.
14. Ongoing or active systemic infection, known human immunodeficiency virus positive, known active hepatitis B virus hepatitis, or known active hepatitis C virus hepatitis.
15. 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.
16. Psychiatric illness/social situation that would limit compliance with study requirements.
17. Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
18. Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment.
19. Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or GI procedure that could interfere with the oral absorption or tolerance of treatment.
20. Diagnosed or treated for another malignancy within 2 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
21. Patient has significant neuropathy within 14 days prior to enrolment.
22. Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrolment.
23. Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent.
24. Participation in clinical trials with other investigational agents not included in this trial, within 21days of the start of this trial and throughout the duration of this trial.
25. Failure to have fully recovered from the reversible effects of prior chemotherapy.
26. Central nervous system involvement

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
assessment of treatment lenalidomide, dexamethasone,MLN9708	MLN9708	-
assessment of treatment lenalidomide, dexamethasone,MLN9708	Lenalidomide	-
assessment of treatment lenalidomide, dexamethasone,MLN9708	Dexamethasone	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
To evaluate the overall response rate after high-dose therapy (prior to consolidation)	after 84 days
To evaluate the overall response rate after induction therapy	after 63 days
To evaluate the quality of stem cell harvest	after 84 days	according to institutional practice, participants must collect a minimum CD34 count of \> 5x106 cells/kg. In case of insufficient collection, collection of a minimum CD34 count of \> 2x106 cells/kg will be allowed.; Thus the number of cells collected will be evaluated
To evaluate the overall response rate after consolidation therapy	after 270 days
To evaluate the safety Evaluate the safety	after 63 days	Descriptive statistics of treatment duration cumulative dose, dose intensity and relative dose intensity will be presented.; Treatment emergent adverse events will be summarized by period (induction, consolidation and maintenance) and overall.; Overall adverse events will be summarized by system organ class and preferred term and by severity (worst toxicity grade owing to the NCI CTCAE v4.0).
To evaluate duration of response, progression-free and overall survival	five years and a half
To evaluate the feasibility of maintenance with MLN9708	after 270 days	number of dose

Trial Locations

Locations (10)

CHRU - Hôpitaux de Brabois; 🇫🇷 Vandoeuvre Les Nancy, France

CHRU Dijon; 🇫🇷 Dijon, France

CHRU - Hôpital du Haut Lévêque; 🇫🇷 Bordeaux, France

Centre hospitalier départemental Vendée; 🇫🇷 La Roche Sur Yon, France

CHRU - Hôpital Claude Huriez; 🇫🇷 Lille, France

Nantes University Hospital; 🇫🇷 Nantes, France

Hôpital Saint-Antoine; 🇫🇷 Paris, France

CHRU - Hôpital Bretonneau; 🇫🇷 Tours, France

Centre Hospitalier Lyon sud; 🇫🇷 Pierre Benite, France

Pole IUC Oncopole CHU; 🇫🇷 Toulouse cedex 9, France