Clinical trial NCT00358020: Melphalan, Prednisone, Thalidomide And Bortezomib In Advanced And Refractory Multiple Myeloma Patients
Official title: A Phase II, Multi-Center, Open Label Study Of Melphalan, Prednisone, Thalidomide And Bortezomib In Advanced And Refractory Multiple Myeloma Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: MYELOMA, THALIDOMIDE, BORTEZOMIB
Lead sponsor: University of Turin, Italy
Sponsor class: OTHER
First posted: 2006-07-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.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.

Primary outcomes:
measure: SAFETY AND EFFICACY
Secondary outcomes:
measure: PROGRESSION FREE SURVIVAL AND OVERALL SURVIVAL
Other outcomes:
Locations:
city: Bolzano
country: Italy
facility: Divisione Di Ematologia, Ospedale Centrale
city: Cosenza
country: Italy
facility: Unità Operativa Complessa Di Ematologia, Presidio Ospedaliero Dell'Annunziata, Azienda Ospedaliera Di Cosenza
city: Palermo
country: Italy
facility: Divisione Di Ematologia E Trapianto Di Midollo Osseo, Azienda Ospedaliera Cervello
city: Reggio Calabria
country: Italy
facility: Divisione Di Ematologia, Ospedali Riuniti
city: Roma
country: Italy
facility: Cattedra E Divisione Di Ematologia, Università Tor Vergata, Ospedale S.Eugenio
city: Torino
country: Italy
facility: Divisione Universitaria Ematologia - Az.Osp. San Giovanni Battista
city: Torino
country: Italy
facility: Ematologia, Azienda Ospedaliera S.Giovanni Battista
Study officials:
affiliation: DIVISIONE DI EMATOLOGIA DELL'UNIVERSITA' DI TORINO, AZIENDA OSPEDALIERA SAN GIOVANNI BATTISTA, TORINO, ITALY
name: MARIO BOCCADORO, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: DIVISONE DI MEATOLOGIA DELL'UNIVERSITA' DI TORINO, AZIENDA OSPEDALIERA SAN GIOVANNI BATTISTA, TORINO, ITALY
name: ANTONIO PALUMBO, MD
role: STUDY_DIRECTOR
References:
citation: Buzaid AC, Durie BG. Management of refractory myeloma: a review. J Clin Oncol. 1988 May;6(5):889-905. doi: 10.1200/JCO.1988.6.5.889.
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.
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. doi: 10.1038/sj.leu.2403196.
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. doi: 10.1056/NEJMoa030288.
citation: 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. doi: 10.1182/blood-2003-04-1045. Epub 2003 Sep 11.