Velcade, Melphalan, Prednisone And Thalidomide Versus Velcade, Melphalan, Prednisone in Multiple Myeloma Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
Fondazione Neoplasie Sangue Onlus
ClinicalTrials.gov Identifier:
NCT01063179
First received: February 4, 2010
Last updated: March 24, 2010
Last verified: March 2010
  Purpose

The proposed study will evaluate whether the combination of VELCADE, Thalidomide , Melphalan and Prednisone (V-MPT), as induction treatment for newly diagnosed elderly MM patients, improves outcomes compared to the combination VELCADE-MP.


Condition Intervention Phase
Multiple Myeloma
Drug: Bortezomib, Melphalan, Prednisone, Thalidomide
Drug: Bortezomib, Melphalan, Prednisone
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 III, MULTI-CENTER, RANDOMIZED OPEN LABEL STUDY OF VELCADE, MELPHALAN, PREDNISONE AND THALIDOMIDE (V-MPT) Versus VELCADE, MELPHALAN, PREDNISONE (V-MP) IN ELDERLY UNTREATED MULTIPLE MYELOMA PATIENTS

Resource links provided by NLM:


Further study details as provided by Fondazione Neoplasie Sangue Onlus:

Primary Outcome Measures:
  • Determine whether the V-MPT combination improves progression free survival (PFS) [ Time Frame: Approximately 24 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine whether the VMPT combination improves:Response rate, Overall Survival rate, Time and duration of response, Assess the safety, Assess the prognostic factors [ Time Frame: Approximately 24 months ] [ Designated as safety issue: Yes ]

Enrollment: 511
Study Start Date: May 2006
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: VMPT
Induction therapy with nine 5-week courses of VELCADE/Melphalan/Prednisone/Thalidomide (V-MPT) followed by maintenance therapy with Thalidomide and VELCADE
Drug: Bortezomib, Melphalan, Prednisone, Thalidomide

Induction therapy:

9 courses with weekly VELCADE (4 doses) in combination with oral Melphalan 9 mg/m2,oral Prednisone 60 mg/m2 once daily on Days 1 to 4 of each course and Thalidomide 50 mg/day continuously. The dose of VELCADE is 1.3 mg/m2 administered as a bolus IV injection, on days 1, 8, 15, 22.

Maintenance therapy:

Thalidomide 50 mg/day continuously in combination with VELCADE 1.3 mg or maximum dose tolerated/m2/2 weeks. The maintenance will be initiated at the end of the 9th course and will be stopped after progression. The median expected duration of the maintenance treatment is approximately 2 years.

Other Names:
  • Bortezomib
  • Velcade
  • Thalidomide
Active Comparator: VMP

Induction therapy with nine 5-week courses of either VELCADE/Melphalan/Prednisone (V-MP).

No maintenance is scheduled.

Drug: Bortezomib, Melphalan, Prednisone
Induction therapy: 9 courses with weekly VELCADE(4 doses) in combination with oral Melphalan 9 mg/m2 and oral Prednisone 60 mg/m2 once daily on Days 1 to 4 of each course. No maintenance therapy is scheduled
Other Names:
  • Boirtezomib
  • velcade

Detailed Description:

This phase III study represents a prospective randomized open label multicenter trial to evaluate whether the combination of VELCADE, Melphalan, Prednisone and Thalidomide (V-MPT), as induction treatment for newly diagnosed elderly MM patients, improves outcomes compared to the combination VELCADE-MP.

Subjects will be randomized in a 1:1 allocation between:

Arm A: 250 patients: V-MPT treatment Arm B: 250 patients: V-MP treatment Patients excluded from randomization are to be registered in Arm C. Patients randomized in arm A (Thalidomide based) will be further enrolled in the sub-study about the DVT prophylaxis.

Patients will be evaluated at scheduled visits in up to 3 study periods: pre-treatment, treatment and long-term follow-up (LTFU).

  1. Pre-treatment period:

    Screening visits, performed at study entry. After providing written informed consent to participate in the study, patients will be evaluated for study eligibility After registration subjects will be randomized.

  2. Treatment period:

    Subjects in Arm A will receive:

    1. Induction therapy:

      nine 5-week courses of VELCADE/Melphalan/Prednisone/Thalidomide (V-MPT)

    2. Maintenance therapy:

    Thalidomide in combination with VELCADE

    Subjects in Arm B will receive:

    1. Induction therapy:

      nine 5-week courses of VELCADE/Melphalan/Prednisone (V-MP)

    2. No maintenance therapy is scheduled At the end of induction treatment or at the time of discontinuation of all study drugs, all patients are to attend study center visits on an every 6 to 8-week basis, until development of confirmed Progressive Disease (PD)
  3. LTFU period:

After development of confirmed PD all patients are to be followed for survival every 3 months via telephone or office visit.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > 65 year old and not a candidate for stem cell transplant, or younger who refuses or is not eligible for high-dose therapy
  • Symptomatic multiple myeloma or asymptomatic multiple myeloma with related organ or tissue damage
  • Presence of measurable disease
  • Karnofsky performance status (PS) > 60%
  • Able to read and complete the HRQOL instruments
  • Agrees to use an acceptable barrier method for contraception for the duration of the study
  • Pretreatment clinical laboratory values within 14 days of randomization:

platelet count ≥ 100x109/L

  • hemoglobin ≥ 8 g/dL
  • absolute neutrophil count (ANC) ≥ 1.0x109/L
  • AST ≤ 2.5 times the upper limit of normal
  • ALT ≤ 2.5 times the upper limit of normal
  • total bilirubin ≤ 1.5 times the upper limit of normal
  • serum creatinine ≤ 2.5mg/dL
  • corrected serum calcium <14 mg/dL (<3.5 mmol/L)
  • Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
  • 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;
  • Males must agree to use barrier contraception (latex condoms) when engaging in reproductive activity during the Treatment Period and for 4 weeks after the last dose.

Exclusion Criteria:

  • Diagnosis of smoldering multiple myeloma or MGUS.
  • Diagnosis of Waldenstrom's disease
  • Prior or current systemic therapy for multiple myeloma including steroids (with exception of emergency use of a short course [maximum 4 days] of steroids before randomization or prior or current use of biphosphonates)
  • Radiation therapy within 30 days before randomization
  • Plasmapheresis within 30 days before randomization
  • Major surgery within 30 days before randomization (Kyphoplasty is not considered major surgery)
  • History of allergic reaction attributable to compounds containing boron or mannitol, or to Thalidomide
  • Peripheral neuropathy Grade 2 or higher, as defined by National Cancer Institute Common Toxicity Criteria (NCI CTC) 3.0
  • Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis
  • Other malignancy within the past 5 years. Exceptions: basal cell or non metastatic squamous cell carcinoma of the skin, cervical carcinoma in situ or FIGO Stage 1 carcinoma of the cervix
  • Concurrent medical condition or disease (e.g., active systemic infection, uncontrolled diabetes, pulmonary disease) that is likely to interfere with study procedures or results, or that in the opinion of the investigator would constitute a hazard for participating in this study
  • Use of any investigational drugs within 30 days before randomization.
  • 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).
  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: NCT01063179

Locations
Italy
A.O.U. S. Giovanni Battista
Torino, Italy, 10126
Sponsors and Collaborators
Fondazione Neoplasie Sangue Onlus
Investigators
Principal Investigator: Mario Boccadoro, MD Divisione di Ematologia dell'Università di Torino, A.O.U. S. Giovanni Battista, Torino;Italy
  More Information

No publications provided by Fondazione Neoplasie Sangue Onlus

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Mario Boccadoro, Fondazione Neoplasie Sangue Onlus
ClinicalTrials.gov Identifier: NCT01063179     History of Changes
Other Study ID Numbers: GIMEMA-MM-03-05, 2005-004745-33
Study First Received: February 4, 2010
Last Updated: March 24, 2010
Health Authority: Italy: Ministry of Health

Keywords provided by Fondazione Neoplasie Sangue Onlus:
Elderly patients
Bortezomib
Thalidomide

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
Melphalan
Bortezomib
Prednisone
Thalidomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Inflammatory Agents
Glucocorticoids

ClinicalTrials.gov processed this record on September 15, 2014