Melphalan, Prednisone, and CC-5013 (Revlimid) as Induction Therapy in Multiple Myeloma

November 29, 2006 updated by: University of Turin, Italy

A Multicenter, Open Label Study of Oral Melphalan, Prednisone, and CC-5013 (Revlimid) (MPR) as Induction Therapy in Elderly Newly Diagnosed Multiple Myeloma Patients

The purpose of this study is to evaluate the safety and efficacy of the association of Melphalan/Prednisone/Revlimid (MPR) as induction treatment for newly diagnosed myeloma patients over age 65 or those under 65 years who refuse or are not eligible for high dose therapy. This association might further increase the response rate achieved by the standard oral MP regimen.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

In Multiple Myeloma patients, the standard treatment is the oral combination of Melphalan and Prednisone (MP). This approach induces a partial response (PR) rate of approximately 50% and a complete remission (CR) rate of 1-5%, with a median remission duration of 18-20 months and a median overall survival of 3 years.

Recently, the combination of oral MP plus thalidomide increased response rate to 80% and complete remission rate to 20%, marked cytoreduction is the first step toward a sustained remission period.

CC-5013 (Revlimid) is a thalidomide analogue, 50000 times more potent than thalidomide in inhibiting TNF-alfa secretion, a potent growth factor for myeloma cells. Revlimid represents a novel class of anti-cancer drugs, it is active in patients with multiple myeloma who are refractory to conventional and high-dose chemotherapy with a response rate of approximately 30%. The association Revlimid plus dexamethasone further increases the response rate induced by Revlimid by an additional 30%.

This study will evaluate the safety and efficacy of the association of Melphalan/Prednisone/Revlimid (MPR) as induction treatment for newly diagnosed myeloma patients over age 65 or those under 65 years who refuse or are not eligible for high dose therapy. This association might further increase the response rate achieved by the standard oral MP regimen.

In the first part of the study (phase I component), different doses of oral Melphalan (0.18-0.25 mg/Kg) associated with Prednisone (MP) will be combined with escalating doses of Revlimid (from 5 mg/day) and administered together. This phase will define the MTD of the association. In the second part of the study (phase II component), 30 patients will be treated with MPR at dose/s defined from phase I component to verify data of response and toxicity.

Study Type

Interventional

Enrollment

54

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Brescia, Italy, 25100
        • Unità Operativa di Ematologia, Spedali Civili
      • Catania, Italy, 95124
        • Reparto di Ematologia, Ospedale Ferrarotto
      • Cosenza, Italy
        • Unità Operativa Complessa Di Ematologia, Presidio Ospedaliero Dell'Annunziata, Azienda Ospedaliera Di Cosenza
      • Genova, Italy, 16132
        • Clinica Ematologica, Ospedale San Martino -Università di Genova
      • Parma, Italy, 43100
        • Cattedra di Ematologia, Dipart. Di Medicina Interna e Scienze Biomediche
      • Roma, Italy, 00161
        • Divisione di Ematologia-Policlinico Umberto I-Università La Sapienza
      • Siena, Italy, 53100
        • Divisione di Ematologia, Azienda Ospedaliera Senese Ospedale A. Sclavo
      • Torino, Italy, 10126
        • Div. Univ. Di Ematologia, Az. Osp. San Giovanni Battista
    • Foggia
      • San Giovanni Rotondo, Foggia, Italy, 71013
        • Unità Operativa di Ematologia Trapianto di Cellule Staminali, Casa Sollievo della Sofferenza

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Patient is of a legally consenting age as defined by local regulations.
  • Age > 65 years or age < 65 years in patients who refuse or are not eligible for high-dose therapy.
  • 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.
  • Female patient is either post-menopausal for 24 consecutive months or surgically sterilised or agree to continuous abstinence from heterosexual sexual contact or willing to use two acceptable method of birth control at the same time (one highly effective method and one additional effective method)(Highly Effective Methods: Intrauterine device -IUD-; Hormonal -birth control pills, injections, implants-; tubal ligation; partner's vasectomy; Additional Effective Methods: Latex condom; Diaphragm; Cervical Cap) for 4 weeks prior to beginning study drug therapy, during study drug therapy (including dose interruption) and for 4 weeks after discontinuation of Lenalomide therapy - 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 Lenalomide therapy.
  • Patient was previously diagnosed with symptomatic multiple myeloma based on standard criteria, 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 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 the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1):
  • Absolute neutrophil count > 1.5 x 109/L without the use of growth factors
  • Platelet count > 75 x 109/L without transfusion support within 7 days before the test.
  • Calculated or measured creatinine clearance: ≥ 20 mL/minute
  • Total bilirubin < 1.5 x the ULN
  • AST (SGOT) and ALT (SGPT) < 2.5 x ULN
  • Corrected serum calcium ≤ 14 mg/dL (3.5 mmol/L

Exclusion Criteria:

  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  • Pregnant or beast feeding females.
  • Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
  • Use of any other concomitant standard/experimental anti-myeloma drug or therapy.
  • Any prior use of CC-5013 or other anti-myeloma therapy.
  • Any of the following laboratory abnormalities:
  • Platelet count < 75 x 109/L.
  • Absolute neutrophil count <1.5 x 109/L.
  • Calculated or measured creatinine clearance <20 mL/minute.
  • Corrected serum calcium >14 mg/dL (3.5 mmol/L).
  • Aspartate transaminase (AST): >2.5 x the upper limit of normal (ULN).
  • Alanine transaminase (AST): > 2.5 x the ULN.
  • Total bilirubin: > 1.5 x the ULN.
  • Known positive for HIV or active infectious hepatitis, type B or C.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
SAFETY AND EFFICACY

Secondary Outcome Measures

Outcome Measure
PROGRESSION FREE SURVIVAL AND OVERALL SURVIVAL

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Turin, Italy

Investigators

  • Principal Investigator: MARIO BOCCADORO, MD, DIVISIONE DI EMATOLOGIA DELL'UNIVERSITA' DI TORINO, AZIENDA OSPEDALIERA SAN GIOVANNI BATTISTA, TORINO, ITALY
  • Study Director: ANTONIO PALUMBO, MD, DIVISIONE UNIVERSITARIA DI EMATOLOGIA, AZIENDA OSPEDALIERA SAN GIOVANNI BATTISTA, TORINO, ITALY

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Study Completion

January 1, 2008

Study Registration Dates

First Submitted

November 2, 2006

First Submitted That Met QC Criteria

November 3, 2006

First Posted (Estimate)

November 6, 2006

Study Record Updates

Last Update Posted (Estimate)

November 30, 2006

Last Update Submitted That Met QC Criteria

November 29, 2006

Last Verified

November 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RV-MM-PI-026
  • MPR

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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