Melphalan, Prednisone, Thalidomide And Bortezomib In Advanced And Refractory Multiple Myeloma Patients

Multiple Myeloma Clinical Trial

Official title:

A Phase II, Multi-Center, Open Label Study Of Melphalan, Prednisone, Thalidomide And Bortezomib In Advanced And Refractory Multiple Myeloma Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00358020
• Other study ID #: X05141
• Secondary ID: MPTV
• Status: Completed
• Phase: Phase 2
• First received: July 27, 2006
• Last updated: November 30, 2006
• Start date: November 2004
• Est. completion date: December 2008

Study information

• Verified date: November 2006
• Source: University of Turin, Italy
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and the efficacy of the association of Melphalan/Prednisone/Thalidomide/VELCADE (MPTV) as salvage treatment in advanced and refractory myeloma patients. This association might further increase the response rate achieved by the standard oral MP regimen.

Description:

In Multiple Myeloma (MM) patients, the conventional treatment is the oral combination melphalan and prednisone (MP). thalidomide has been widely used in myeloma, it has been proved clinical effective in refractory myeloma patients, it acts sinergistically in association with dexamethasone. In newly diagnosed patients, the combination oral MP plus thalidomide increased the partial and complete response rate.Bortezomib represents a novel class of anti-cancer drugs, it is active in patient with multiple myeloma who are refractory to conventional chemotherapy. In a preliminary report, the combination of VELCADE and Thalidomide induced a remarkable 60% PR rate in advanced refractory myeloma patients. This study will evaluate the safety and the efficacy of the association of Melphalan/ Prednisone/Thalidomide/VELCADE (MPTV) as salvage treatment in advanced and refractory myeloma patients. This association might further increase the response rate achieved by the standard oral MP regimen.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient is of a legally consenting age as defined by local regulations.

• 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 or surgically sterilized or willing to use an acceptable 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.

• Male patient agrees to use an acceptable method for contraception (i.e., condom or abstinence) for the duration of the study.

• Patient was previously diagnosed with multiple myeloma based on standard criteria.

• Patient is relapsed or refractory after one or two lines of treatment including high-dose chemotherapy with stem cell support, conventional poli-chemotherapy, thalidomide- and melphalan-based regimens.

• Patient 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.

• Patient has a Karnofsky performance status =60%.

• Patient has a life-expectancy >3 months.

• Patient has the following laboratory values within 14 days before Baseline (day 1 of the Cycle 1, before study drug administration):

• Platelet count =75 x 109/L without transfusion support within 7 days before the test.

• Absolute neutrophil count (ANC) = 0.75 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 (AST): = 2.5 x the ULN.

• Total bilirubin: = 1.5 x the ULN.

• Calculated or measured creatinine clearance: =20 mL/minute.

Exclusion Criteria:

• Patient has an absolute neutrophil count <0.75 × 109/L within 14 days before enrollment.

• Patient has a calculated or measured creatinine clearance <20 mL/minute within 14 days before enrollment.

• Patient has =Grade 2 peripheral neuropathy within 14 days before enrollment.

• Patient has known hypersensitivity to bortezomib, boron, mannitol or thalidomide.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• THALIDOMIDE

• BORTEZOMIB

Locations

Country	Name	City	State
Italy	Divisione Di Ematologia, Ospedale Centrale	Bolzano
Italy	Unità Operativa Complessa Di Ematologia, Presidio Ospedaliero Dell’Annunziata, Azienda Ospedaliera Di Cosenza	Cosenza
Italy	Divisione Di Ematologia E Trapianto Di Midollo Osseo, Azienda Ospedaliera Cervello	Palermo
Italy	Divisione Di Ematologia, Ospedali Riuniti	Reggio Calabria
Italy	Cattedra E Divisione Di Ematologia, Università Tor Vergata, Ospedale S.Eugenio	Roma
Italy	Divisione Universitaria Ematologia - Az.Osp. San Giovanni Battista	Torino
Italy	Ematologia, Azienda Ospedaliera S.Giovanni Battista	Torino

Sponsors (1)

Lead Sponsor	Collaborator
University of Turin, Italy

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Barlogie B, Shaughnessy J, Tricot G, Jacobson J, Zangari M, Anaissie E, Walker R, Crowley J. Treatment of multiple myeloma. Blood. 2004 Jan 1;103(1):20-32. Epub 2003 Sep 11. Review. — View Citation

Buzaid AC, Durie BG. Management of refractory myeloma: a review. J Clin Oncol. 1988 May;6(5):889-905. Review. — View Citation

Palumbo A, Bringhen S, Bertola A, Cavallo F, Falco P, Massaia M, Bruno B, Rus C, Barbui A, Caravita T, Musto P, Pescosta N, Rossini F, Vignetti M, Boccadoro M. Multiple myeloma: comparison of two dose-intensive melphalan regimens (100 vs 200 mg/m(2)). Leukemia. 2004 Jan;18(1):133-8. — View Citation

Palumbo A, Giaccone L, Bertola A, Pregno P, Bringhen S, Rus C, Triolo S, Gallo E, Pileri A, Boccadoro M. Low-dose thalidomide plus dexamethasone is an effective salvage therapy for advanced myeloma. Haematologica. 2001 Apr;86(4):399-403. — View Citation

Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, Rajkumar SV, Srkalovic G, Alsina M, Alexanian R, Siegel D, Orlowski RZ, Kuter D, Limentani SA, Lee S, Hideshima T, Esseltine DL, Kauffman M, Adams J, Schenkein DP, Anderson KC. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 2003 Jun 26;348(26):2609-17. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	SAFETY AND EFFICACY
Secondary	PROGRESSION FREE SURVIVAL AND OVERALL SURVIVAL