Cyclophosphamide, Lenalidomide and Dexamethasone (CRD) Versus Melphalan (200 mg/m2) Followed By Autologous Stem Cell Transplant (ASCT) In Newly Diagnosed Multiple Myeloma Subjects

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2010 by Fondazione Neoplasie Sangue Onlus.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Fondazione Neoplasie Sangue Onlus
ClinicalTrials.gov Identifier:
NCT01091831
First received: March 22, 2010
Last updated: March 23, 2010
Last verified: March 2010
  Purpose

This is a multicenter, randomized, open label study designed to compare the efficacy and safety of lenalidomide with low-dose alkylating agents versus high-dose melphalan followed by stem cell support in newly diagnosed symptomatic MM patients who are 65 years of age or younger.


Condition Intervention Phase
Multiple Myeloma
Drug: Cyclophosphamide
Drug: Lenalidomide
Drug: Dexamethasone
Drug: Melphalan
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3, Multicentre, Randomized, Controlled Study to Determine the Efficacy and Safety of Cyclophosphamide, Lenalidomide and Dexamethasone (CRD) Versus Melphalan (200 mg/m2) Followed By Stem Cell Transplant In Newly Diagnosed Multiple Myeloma Subjects

Resource links provided by NLM:


Further study details as provided by Fondazione Neoplasie Sangue Onlus:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 380
Study Start Date: July 2009
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: CRD
Oral therapy with Cyclophosphamide, Lenalidomide and Dexamethasone.
Drug: Cyclophosphamide
Cyclophosphamide will be given orally at the dose of 300 mg/m2 on days 1, 8, 15 for 6 cycles every 28 days
Drug: Lenalidomide
Lenalidomide will be given orally at the dose of 25 mg/d for 21 days followed by a 7 days rest period (day 22 to 28)for 6 cycles every 28 days
Drug: Dexamethasone
Dexamethasone will be given orally at the dose of 40 mg on days 1, 8, 15, 22 for 6 cycles every 28 days
Active Comparator: MEL200
High dose Melphalan therapy (200 mg/m2) followed by stem cell support for 2 cycles every 4 months (for 1 cycle if at least VGPR was achieved after the 1st MEL200)
Drug: Melphalan
Melphalan will be given iv at the dose of 200 mg/m2 for 1 day followed by stem cell support. The second MEL200 was performed 120 days after the first if ≤ PR was achieved after the 1st MEL200.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • Women of child-bearing potential must agree to use 2 methods of contraception: 1 effective (for example hormonal or tubal ligation) and 1 barrier (for example latex condom, diaphragm) for at least 4 weeks before starting the therapy, during the Treatment Period, and for 4 weeks after the last dose of lenalidomide
  • 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.
  • Negative serum beta-human chorionic gonadotropin ( beta-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
  • Patient was diagnosed with symptomatic multiple myeloma based on standard criteria (10), 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 HBV, HCV and HIV negative test.
  • Patients must have normal ECG and NYHA ≤ 2; an evaluation of ejection fraction by ECHO or MUGA is optional
  • Patients must normal chest X ray; an evaluation of pulmonary function studies on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) is optional.
  • 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: ≥ 20 mL/minute
    • Patient has a baseline bone marrow sample available for cytogenetics, that will be processed and eventually centralized.

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 women. A serum β-hCG pregnancy test must be performed at the Screening visit, for female patients of child-bearing potential. If the test is positive, the patient must be excluded from the study. Confirmation that the patient is not pregnant must be established by a negative serum or urinary pregnancy test with the result obtained 1 day prior to the Baseline visit (or the day of the visit if results are available before drug delivery). A pregnancy test is not required for naturally post-menopausal women (who have not had menses at any time in the preceding 24 consecutive months) or surgically sterilised women (hysterectomy, bilateral ovariectomy, bilateral salpingectomy);
  • 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)
  • Patients previously diagnosed as bearing deep venous thrombosis or arterial thromboembolic event within the latest 12 months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01091831

Contacts
Contact: Antonio Palumbo, MD 011 6336728 ext +39 appalumbo@yahoo.com
Contact: Mario Boccadoro, MD 011 6336728 ext +39 mario.boccadoro@unito.it

Locations
Italy
Division of Hematology, Molinette Hospital Recruiting
Torino, Italy, 10126
Contact: Antonio Palumbo, MD    011 6336728 ext +39    appalumbo@yahoo.com   
Contact: Mario Boccadoro, MD    011 6336728 ext +39    mario.boccadoro@unito.it   
Sponsors and Collaborators
Fondazione Neoplasie Sangue Onlus
Investigators
Principal Investigator: Antonio Palumbo, MD Division of Hematology, Molinette Hospital
  More Information

No publications provided

Responsible Party: Fondazione Neoplasie Sangue Onlus, Prof. Mario Boccadoro
ClinicalTrials.gov Identifier: NCT01091831     History of Changes
Other Study ID Numbers: RV-MM-EMN-441
Study First Received: March 22, 2010
Last Updated: March 23, 2010
Health Authority: Italy: Institutional Review Board
Italy: Ministry of Health
Australia: Institutional Review Board
Czech Republic: Institutional Review Board

Keywords provided by Fondazione Neoplasie Sangue Onlus:
Multiple Myeloma
Lenalidomide
High dose melphalan
Mobilization
CD 34
Newly Diagnosed patients

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Melphalan
Thalidomide
Lenalidomide
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on September 11, 2014