MPRvsMEL200: Lenalidomide Melphalan and Prednisone Versus High Dose Melphalan in Newly Diagnosed Multiple Myeloma Patients

Sponsor

Fondazione EMN Italy Onlus (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00551928

Collaborator

(none)

402

Enrollment

Location

Arms

180

Duration (Months)

2.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To compare the efficacy of the combination of lenalidomide with low-dose melphalan versus high-dose melphalan in newly diagnosed, symptomatic MM patients.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma Newly Diagnosed Patients	Drug: Melphalan Drug: Lenalidomide Drug: Prednisone Drug: Melphalan	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

402 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A PHASE 3, MULTICENTRE, RANDOMIZED, CONTROLLED STUDY TO DETERMINE THE EFFICACY AND SAFETY OF LENALIDOMIDE, MELPHALAN AND PREDNISONE (MPR) Versus MELPHALAN (200 mg/m2) FOLLOWED BY STEM CELL TRANSPLANT IN NEWLY DIAGNOSED MULTIPLE MYELOMA SUBJECTS

Study Start Date :

Jun 1, 2007

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A Oral therapy with Lenalidomide Melphalan and Prednisone.	Drug: Lenalidomide Six months of oral therapy with Lenalidomide 10mg/day given 21 days in every 28 days cycle with the combination ofMelphalan and steroids (day 22 to 28), for 6 cycles every 28 days. Drug: Prednisone Given orally at the dose of 2 mg/Kg for 4 days followed by a 24 day rest period (days 5 to 28), for 6 cycles every 28 days Drug: Melphalan Melphalan will be given orally at the dose of 0.18 mg/Kg for 4 days, followed by a 24 days rest period (day 5 to 28)for 6 cycles every 28 days
Active Comparator: B High dose Melphalan therapy (200mg/sm)with autologous stem cell support, for 2 cycles every 4 months (only 1 cycle if the patient reached almost a VGPR after the 1st MEL200)	Drug: Melphalan High dose Melphalan 200mg/sm with autologous stem cell support

Arm

Intervention/Treatment

Active Comparator: A

Oral therapy with Lenalidomide Melphalan and Prednisone.

Drug: Lenalidomide

Six months of oral therapy with Lenalidomide 10mg/day given 21 days in every 28 days cycle with the combination ofMelphalan and steroids (day 22 to 28), for 6 cycles every 28 days.

Drug: Prednisone

Given orally at the dose of 2 mg/Kg for 4 days followed by a 24 day rest period (days 5 to 28), for 6 cycles every 28 days

Drug: Melphalan

Melphalan will be given orally at the dose of 0.18 mg/Kg for 4 days, followed by a 24 days rest period (day 5 to 28)for 6 cycles every 28 days

Active Comparator: B

High dose Melphalan therapy (200mg/sm)with autologous stem cell support, for 2 cycles every 4 months (only 1 cycle if the patient reached almost a VGPR after the 1st MEL200)

Drug: Melphalan

High dose Melphalan 200mg/sm with autologous stem cell support

Outcome Measures

Primary Outcome Measures

Progression free survival [5 years]

Secondary Outcome Measures

Over all survival [5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient is, in the investigator(s) opinion, willing and able to comply with the protocol requirements.
Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
Patient is 65 years old or younger at the time of signing the informed consent
Female patient is either post-menopausal or surgically sterilized or willing to use an acceptable double method of birth control (i.e., a hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
Negative serum β-human chorionic gonadotropin ( β-HCG) pregnancy test both 24 hours prior to beginning of therapy and then at 4 weeks intervals in women with regular menstrual cycles or every 2 weeks in women with irregular menstrual cycles during study treatment for subjects of childbearing potential
Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) during study drug therapy (including dose interruption) and for 4 weeks after discontinuation of lenalidomide therapy.
Patient was diagnosed with symptomatic multiple myeloma based on standard criteria (9), and has measurable disease, defined as follows: any quantifiable serum monoclonal protein value (generally, but not necessarily, greater than 1 g/dL of IgG M-Protein and greater than 0.5 g/dL of IgA M-Protein) and, where applicable, urine light-chain excretion of >200 mg/24 hours; measurable plasmacytoma > 2 cm as determined by clinical examination or applicable radiographs (i.e. MRI, CT-Scan); bone marrow plasma cells>10%.
Patient has a Karnofsky performance status ≥ 60%.
Patient has a life-expectancy > 6 months
Patient has not active infectious hepatitis type B or C, and has HIV negative test
Patients must have an ejection fraction by ECHO or MUGA > 50% performed within 60 days prior to registration
Patients must have adequate pulmonary function studies > 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > 50% of predicted. Patients unable to complete pulmonary function tests because of myeloma-related chest pain, must have a high resolution CT scan of the chest and must also have acceptable arterial blood gases defined as P02 greater than 70.
Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1):
Platelet count ≥ 75 x 109/L without transfusion support within 7 days before the test.
Absolute neutrophil count (ANC) ≥ 1.5 x 109/L without the use of growth factors.
Corrected serum calcium ≤ 14 mg/dL (3.5 mmol/L).
Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal (ULN).
Alanine transaminase (ALT): ≤ 2.5 x the ULN.
Total bilirubin: ≤ 1.5 x the ULN.
Calculated or measured creatinine clearance: ≥ 30 mL/minute
Patient has a baseline bone marrow sample available for cytogenetics, that will be processed and eventually centralized within each country.

Exclusion Criteria:

Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid; < to the equivalent of dexamethasone 40 mg/day for 4 days).
Any serious medical condition, including the presence of laboratory abnormalities, which places the subject at an unacceptable risk if he or she participates in this study or confounds the experimental ability to interpret data from the study.
Pregnant or lactating females.
Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for ≥ 3 years. Exceptions include the following: Basal cell carcinoma of the skin, Squamous cell carcinoma of the skin, Carcinoma in situ of the cervix, Carcinoma in situ of the breast, Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)
Neuropathy of ≥ grade 2 severity.
Patients previously diagnosed as bearing deep venous thrombosis or arterial thromboembolic event within the latest 12 months, or bearing a clear indication for anti-platelet or anticoagulant therapy or bearing a high risk of bleeding complications are ineligible for the sub-study protocol.