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

• ClinicalTrials.gov Identifier: NCT00551928
• Recruitment Status: Active, not recruiting
• First Posted: October 31, 2007
• Last Update Posted: June 29, 2023
• Sponsor: Fondazione EMN Italy Onlus
• Information provided by (Responsible Party): Fondazione EMN Italy Onlus

Tracking Information

• First Submitted Date: October 30, 2007
• First Posted Date: October 31, 2007
• Last Update Posted Date: June 29, 2023
• Study Start Date: June 2007
• Actual Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 16, 2010): Progression free survival [ Time Frame: 5 years ]

Original Primary Outcome Measures (submitted: October 30, 2007)

• Progression free survival [ Time Frame: 5 years ]
• Response rate [ Time Frame: 1 year ]
• Duration of response [ Time Frame: 5 years ]

• Current Secondary Outcome Measures (submitted: October 30, 2007): Over all survival [ Time Frame: 5 years ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Lenalidomide Melphalan and Prednisone Versus High Dose Melphalan in Newly Diagnosed Multiple Myeloma Patients
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Multiple Myeloma
• Newly Diagnosed Patients

Intervention

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

Study Arms

• Active Comparator: A
  Oral therapy with Lenalidomide Melphalan and Prednisone.
  Interventions:

  • Drug: Lenalidomide
  • Drug: Prednisone
  • Drug: Melphalan
• 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)
  Intervention: Drug: Melphalan

Publications *

• Rutjes AW, Porreca E, Candeloro M, Valeriani E, Di Nisio M. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2020 Dec 18;12(12):CD008500. doi: 10.1002/14651858.CD008500.pub5.
• Montefusco V, Gay F, Spada S, De Paoli L, Di Raimondo F, Ribolla R, Musolino C, Patriarca F, Musto P, Galieni P, Ballanti S, Nozzoli C, Cascavilla N, Ben-Yehuda D, Nagler A, Hajek R, Offidani M, Liberati AM, Sonneveld P, Cavo M, Corradini P, Boccadoro M. Outcome of paraosseous extra-medullary disease in newly diagnosed multiple myeloma patients treated with new drugs. Haematologica. 2020 Jan;105(1):193-200. doi: 10.3324/haematol.2019.219139. Epub 2019 Jun 20.
• Cerrato C, Di Raimondo F, De Paoli L, Spada S, Patriarca F, Crippa C, Mina R, Guglielmelli T, Ben-Yehuda D, Oddolo D, Nozzoli C, Angelucci E, Cascavilla N, Rizzi R, Rocco S, Baldini L, Ponticelli E, Marcatti M, Cangialosi C, Caravita T, Benevolo G, Ria R, Nagler A, Musto P, Tacchetti P, Corradini P, Offidani M, Palumbo A, Petrucci MT, Boccadoro M, Gay F. Maintenance in myeloma patients achieving complete response after upfront therapy: a pooled analysis. J Cancer Res Clin Oncol. 2018 Jul;144(7):1357-1366. doi: 10.1007/s00432-018-2641-5. Epub 2018 Apr 19.
• Palumbo A, Cavallo F, Gay F, Di Raimondo F, Ben Yehuda D, Petrucci MT, Pezzatti S, Caravita T, Cerrato C, Ribakovsky E, Genuardi M, Cafro A, Marcatti M, Catalano L, Offidani M, Carella AM, Zamagni E, Patriarca F, Musto P, Evangelista A, Ciccone G, Omede P, Crippa C, Corradini P, Nagler A, Boccadoro M, Cavo M. Autologous transplantation and maintenance therapy in multiple myeloma. N Engl J Med. 2014 Sep 4;371(10):895-905. doi: 10.1056/NEJMoa1402888.
• Dunavin NC, Wei L, Elder P, Phillips GS, Benson DM Jr, Hofmeister CC, Penza S, Greenfield C, Rose KS, Rieser G, Merritt L, Ketcham J, Heerema N, Byrd JC, Devine SM, Efebera YA. Early versus delayed autologous stem cell transplant in patients receiving novel therapies for multiple myeloma. Leuk Lymphoma. 2013 Aug;54(8):1658-64. doi: 10.3109/10428194.2012.751528. Epub 2012 Dec 31.
• Larocca A, Cavallo F, Bringhen S, Di Raimondo F, Falanga A, Evangelista A, Cavalli M, Stanevsky A, Corradini P, Pezzatti S, Patriarca F, Cavo M, Peccatori J, Catalano L, Carella AM, Cafro AM, Siniscalchi A, Crippa C, Petrucci MT, Yehuda DB, Beggiato E, Di Toritto TC, Boccadoro M, Nagler A, Palumbo A. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood. 2012 Jan 26;119(4):933-9; quiz 1093. doi: 10.1182/blood-2011-03-344333. Epub 2011 Aug 11.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 16, 2010): 402
• Original Estimated Enrollment (submitted: October 30, 2007): 386
• Estimated Study Completion Date: June 2025
• Actual Primary Completion Date: June 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Italy
• Removed Location Countries: Israel

Administrative Information

• NCT Number: NCT00551928
• Other Study ID Numbers: RV-MM-PI-209
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Fondazione EMN Italy Onlus
• Original Responsible Party: Not Provided
• Current Study Sponsor: Fondazione EMN Italy Onlus
• Original Study Sponsor: Sheba Medical Center
• Collaborators: Not Provided

Investigators

• Principal Investigator: Francesca Gay, MD; AOU Città della Salute e della Scienza di Torino

• PRS Account: Fondazione EMN Italy Onlus
• Verification Date: June 2023