GEM05 for Patients With Multiple Myeloma More Than 65 Years Old

This study has been completed.
Sponsor:
Information provided by:
PETHEMA Foundation
ClinicalTrials.gov Identifier:
NCT00443235
First received: March 2, 2007
Last updated: September 16, 2011
Last verified: September 2011
  Purpose

The primary objective is to analyze and compare the efficacy, the response rate, the CR and the response rate duration of both induction treatments and both maintenance treatments


Condition Intervention Phase
Multiple Myeloma
Drug: Melphalan/Prednisone/Velcade
Drug: Thalidomide/Prednisone/Velcade
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 National, Open-Label, Multicenter, Randomized, Comparative Phase III Study of Induction Treatment With Melphalan/Prednisone/Velcade Versus Thalidomide / Prednisone / Velcade and Maintenance Treatment With Thalidomide / Velcade Versus Prednisone / Velcade in Untreated Patients With Multiple Myeloma More Than 65 Years Old.

Resource links provided by NLM:


Further study details as provided by PETHEMA Foundation:

Primary Outcome Measures:
  • The primary objective is to analyze and compare the efficacy, the response rate, the CR and the response rate duration of both induction treatments and both maintenance treatments [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 260
Study Start Date: March 2005
Study Completion Date: December 2009
Primary Completion Date: March 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A

One cycle:

Melfalan, 9 mg/m2 v.o days 1 to 4 Prednisone, 60 mg/m2 v.o days 1 to 4 Velcade, 1,3 mg/m2 iv (days 1, 4, 8, 11, 22, 25, 29 and 32) Five cycles: Melfalán, 9 mg/m2 vo, days 1 to 4 Prednisone, 60 mg/m2 v.o days 1 to 4, Velcade,1,3 mg/ m2 iv (days 1, 8, 15 and 22)

Drug: Melphalan/Prednisone/Velcade

One cycle:

Melfalan, 9 mg/m2 v.o days 1 to 4 Prednisone, 60 mg/m2 v.o days 1 to 4 Velcade, 1,3 mg/m2 iv (days 1, 4, 8, 11, 22, 25, 29 and 32) Five cycles: Melfalán, 9 mg/m2 vo, days 1 to 4 Prednisone, 60 mg/m2 v.o days 1 to 4, Velcade,1,3 mg/ m2 iv (days 1, 8, 15 and 22)

Experimental: B

One cycle:

Thalidomide,day 1 cycle 1 v.o (50 mg). If toxicity < grade 2, dose will be increased to 100 mg on day 15 cycle 1 Prednisona, 60 mg/m2 vo, days 1 to 4, Velcade, 1,3 mg/ m2 iv (days 1, 4, 8, 11, 22, 25, 29 and 32)

Five cycles:

Thalidomide, 100 mg vo all days, Prednisone, 60 mg/m2 vo days 1 to 4, Velcade, 1,3 mg/ m2 iv (days 1, 8, 15 and 22)

Drug: Thalidomide/Prednisone/Velcade

One cycle:

Thalidomide,day 1 cycle 1 v.o (50 mg). If toxicity < grade 2, dose will be increased to 100 mg on day 15 cycle 1 Prednisona, 60 mg/m2 vo, days 1 to 4, Velcade, 1,3 mg/ m2 iv (days 1, 4, 8, 11, 22, 25, 29 and 32)

Five cycles:

Thalidomide, 100 mg vo all days, Prednisone, 60 mg/m2 vo days 1 to 4, Velcade, 1,3 mg/ m2 iv (days 1, 8, 15 and 22)


Detailed Description:

A total of up to 260 patients > 65 years old diagnosed of Multiple Myeloma with symptomatic disease and that have not received previous chemotherapy for MM will be included.

Patients will be evaluated at scheduled visits in up to three study periods: Pre-treatment, Treatment and Follow up.

The Pre-treatment includes Screening and baseline visits. After providing informed consent, patients will be evaluated for study eligibility and then Patients will be randomized one to one to receive Melphalan+Prednisone+Velcade (Group A) or Thalidomide+Prednisone+Velcade (Group B). All of them will received the induction treatment up to 30 weeks. After 4 weeks, without progression and unacceptable toxicity, Patients will be again randomized one to one to receive maintenance treatment: Thalidomide+Velcade (Group M1) or Prednisone+Velcade (Group M2) during three years.

Once the treatment period has finished a follow up will be carry out. During this period we will evaluated response, progression-free survival and global survival every three months.

  Eligibility

Ages Eligible for Study:   66 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must be able to comply with the protocol requirements.
  • Must voluntary sign the informed consent before performance of any study-related procedure not part of normal medical care, with the understanding it can be withdrawn at any time without prejudice to future medical care.
  • Age > 65 years.
  • Patient recently diagnosed with symptomatic Multiple Myeloma based on standard criteria28 and that has not received any previous chemotherapy treatment for Multiple Myeloma Some steroid doses or bisphosphonates are allowed for emergencies before starting induction treatment.
  • Patient has measurable disease, defined as follows:

For secretory multiple myeloma, measurable disease is defined as any quantifiable serum monoclonal protein value and, where applicable, urine light-chain excretion of ≥ 200 mg/24 hours.

  • Patient has a ECOG performance status < 2
  • Patient has a life-expectancy >3 months.
  • Patient has the following laboratory values before beginning induction treatment:

Platelet count ≥ 50000/mm3, hemoglobin ≥ 8 g/dl and absolute neutrophil count ≥ 1000/mm3. Lower values are allowed if they are due to marrow infiltration.

Corrected serum calcium <14mg/dl. Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal. Alanine transaminase (ALT): ): ≤ 2.5 x the upper limit of normal. Total bilirubin: ≤1.5 x the upper limit of normal. Serum creatinine ≤ 2 mg/dl.

Exclusion Criteria:

  • Patients previously received treatment to Multiple Myeloma, except steroids doses for urgency or bisphosphonates.
  • Non-secretor Myeloma
  • Patients with < Grade 2 peripheral neuropathy within 14 days before enrolment.
  • Patient had major surgery within 4 weeks before enrolment.
  • Patient has hypersensitivity to bortezomib, boron or mannitol.
  • Patient has received other investigational drugs within 30 days before enrolment.
  • Patient is known to be seropositive for the human immunodeficiency virus (HIV), Hepatitis B surface antigen-positive or active hepatitis C infection.
  • Patient had a myocardial infarction within 6 months of enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  • Patient is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.
  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: NCT00443235

  Hide Study Locations
Locations
Spain
Hospital Royo Villanova
Zaragoza, Aragón, Spain
Complejo Hospitalario Universitario de Albacete
Albacete, Spain
Fundación Hospital Alcorcón
Alcorcón, Spain
Hospital Nuestra Señora de Sonsoles
Avila, Spain
Hospital Regional Universitario Infanta Cristina
Badajoz, Spain
Hospital de Badalona Germans Trias i Pujol
Badalona, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Hospital Clinic i Provincial de Barcelona
Barcelona, Spain
Hospital del Mar
Barcelona, Spain
Hospital Vall D'Hebron
Barcelona, Spain
Hospital de Basurto
Basurto, Spain
Hospital de Cruces
Bilbao, Spain
Hospital General de Castellón
Castellón, Spain
Hospital Nuestra Señora de Alarcos
Ciudad Real, Spain
Hospital Virgen de la Luz
Cuenca, Spain
Hospital Virgen del Puerto
Cáceres, Spain
Hospital Donostia
Donostia, Spain
Hospital General de Elda
Elda, Spain
Institut Català d'Oncologia,
Gerona, Spain
Hospital Universitario de Getafe
Getafe, Spain
Hospital General de Guadalajara
Guadalajara, Spain
Hospital de San Jorge
Huesca, Spain
Hospital General de Lanzarote
Lanzarote, Spain
Complejo Hospitalario Xeral-Calde
Lugo, Spain
Hospital Doce de Octubre
Madrid, Spain
Clínica Moncloa
Madrid, Spain
Hospital Clínico Universitario San Carlos
Madrid, Spain
Hospital Universitario La Paz
Madrid, Spain
Clínica Rúber
Madrid, Spain
Hospital Universitario La Princesa
Madrid, Spain
Hospital Ramón y Cajal
Madrid, Spain
Hospital Central de la Defensa
Madrid, Spain
Fundación Jiménez Díaz
Madrid, Spain
Clínica Puerta de Hierro
Madrid, Spain
Althaia, Xarxa Asistencial de Manresa
Manresa, Spain
Fundación Hospital Sant Joan de Déu de Martorell
Martorell, Spain
Hospital General Morales Meseguer
Murcia, Spain
Hospital Virgen del Castillo de Yecla
Murcia, Spain
Hospital Santa María del Rosell
Murcia, Spain
Hospital de Mérida
Mérida, Spain
Hospital de Móstoles
Móstoles, Spain
Hospital de Gran Canaria Doctor Negrín
Palma de Gran Canaria, Spain
Complejo Asistencial Son Dureta
Palma de Mallorca, Spain
Hospital Son Llatzer
Palma de Mallorca, Spain
Hospital Verge del Toro
Palma de Mallorca, Spain
Clínica Universitaria de Navarra
Pamplona, Spain
Hospital de Navarra
Pamplona, Spain
Hospital Virgen del Camino
Pamplona, Spain
Complejo Hospitalario de Pontevedra_Hospital Provincial
Pontevedra, Spain
Complejo Hospitalario de Pontevedra_Hospital Montecelo
Pontevedra, Spain
Corporació Sanitaria Parc Taulí
Sabadell, Spain
Hospital de Sagunto
Sagunto, Spain
Hospital Clínico de Salamanca
Salamanca, Spain
Hospital San Pedro de Alcántara
San Pedro de Alcántara, Spain
Clínica Sant Camil
Sant Pere de Ribes, Spain
Hospital Universitario Marqués de Valdecilla
Santander, Spain
Complejo Hospitalario Universitario de Santiago
Santiago de Compostela, Spain
Hospital General de Segovia
Segovia, Spain
Hospital Joan XXIII
Tarragona, Spain
Hospital Universitario de Canarias
Tenerife, Spain
Hospital Nuestra Señora del Prado
Toledo, Spain
Hospital Virgen de la Salud
Toledo, Spain
Fundación Instituto Valenciano de Oncología
Valencia, Spain
Hospital Arnau de Vilanova
Valencia, Spain
Hospital Universitario La Fe
Valencia, Spain
Hospital Clínico Universitario de Valencia
Valencia, Spain
Hospital General Básico de la Defensa
Valencia, Spain
Hospital Francesc de Borja
Valencia, Spain
Hospital Clínico Universitario de Valladolid
Valladolid, Spain
Hospital Comarcal Pius de Valls
Valls, Spain
Complejo Hospitalario Universitario de Vigo
Vigo, Spain
Comarcal de Vinaros
Vinaros, Spain
Hospital Txagorritxu
Vitoria, Spain
Hospital de Galdakao
Vizcaya, Spain
Hospital Virgen de la Concha
Zamora, Spain
Hospital Clínico Universitario Lozano Blesa
Zaragoza, Spain
Hospital Miguel Servet
Zaragoza, Spain
Sponsors and Collaborators
PETHEMA Foundation
Investigators
Principal Investigator: Lahuerta Juan josé, Dr Hospital 12 de Octubre
  More Information

Additional Information:
Publications:
1. Greenlee RT, Murray T, Bolden S , Wingo PA. Cancer Statistics, 2000. CA Cancer J Clin 2000; 50: 7-33.
2. Longo D. Plasma cell disorders. In : Fauce A, et al. Ed. Harrison's Principles of Internal Medicine. 14th Ed. New York, New York: Mc Graw-Hill; 1998: 712-718.
14. Paul Richardson et al. Bortezomib Demonstrates Superior Efficacy to High-Dose Dexamethasone in Relapsed Multiple Myeloma: Final Report of the APEX Study. Blood 2004; 104(11):Abstract number 336.5
18. Antonio Palumbo, Alessandra Bertola, Pellegrino Musto, Tommaso Caravita, Vincenzo Callea, Clotilde Cangialosi, Anna Marina Liberati, Pasquale Niscola, Lucio Catalano, Mariella Grasso, Vito Michele Lauta, Maria Concetta Petti, Sergio Morandi, Monica Galli, Sara Bringhen, Federica Cavallo, Patrizia Falco, Mario Boccadoro. A Prospective Randomized Trial of Oral Melphalan, Prednisone, Thalidomide (MPT) vs Oral Melphalan, Prednisone (MP): An Interim Analysis. Blood 2004. Volume 104, issue 11.Abstract number 207
19. Maurizio Zangari, Bart Barlogie, Joth Jacobson, Erik Rasmussen, Michael Burns, Bob Kordsmeier, John D. Shaughnessy, Elias J. Anaissie, Raymond Thertulien, Athanasios Fassas, Choon-Kee Lee, David Schenkein, Jerome B. Zeldis, Guido Tricot. VTD Regimen Comprising Velcade (V) + Thalidomide (T) and Added DEX (D) for Non-Responders to V + T Effects a 57% PR Rate among 56 Patients with Myeloma (M) Relapsing after Autologous Transplant. Blood 2003, Volume 102, issue 11. Abstract number 830
20. Jagannath S, Brian D, Wolf j, Camacho E, Irwin D, Lutzky J, Mckinley M, Gabayan E, Mazumder A, Crowley K, Sckenkein D. A phase 2 study of Bortezomib as first-line therapy in patients with multiple myeloma. Blood 2004; 104(11). Abstract number 333
21. Alexanian R, Wang L, Weber D, Delasalle K. VTD (Velcade, Thalidomide, Dexamethasone) as primary therapy for newly-diagnosed multiple myeloma. Blood 2004; 104(11). Abstract number 210
Whealthy K (On behalf of the Myeloma Trialists`Collaborative Group). Which myeloma patients benefit from interferon therapy?. An overview of 24 randomised trials with 4,000 patients, Br J Haematol 1998; 102: 140
33. Fayers P, Aaonson N, Bjordal K, Curran D, Groenvold M, on behalf of the EORTC Quality of life study group. EORTC QLQ-C30 Scoring Manual: 2nd Ed. 1999. ISBN 2-930064-16-1.1

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

Responsible Party: pethema
ClinicalTrials.gov Identifier: NCT00443235     History of Changes
Other Study ID Numbers: 2005-001111-21
Study First Received: March 2, 2007
Last Updated: September 16, 2011
Health Authority: Spain: Ministry of Health

Keywords provided by PETHEMA Foundation:
Older patients
untreated patients

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Bortezomib
Melphalan
Prednisone
Thalidomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Glucocorticoids
Growth Inhibitors
Growth Substances

ClinicalTrials.gov processed this record on October 29, 2014