Clinical trial NCT00461747: GEM05 for Patients With Multiple Myeloma Under 65 Years
Official title: A National, Open-Label, Multicenter, Randomized, Comparative Phase III Study of Induction Treatment With VBMCP-VBAD/Velcade Versus Thalidomide / Dexamethasone Versus Velcade / Thalidomide / Dexamethasone Followed by High Dose Intensive Therapy With Autologous Hemopoietic Stem Cell Support and Maintenance Treatment With Interferon-a Versus Thalidomide Versus Thalidomide / Velcade in Untreated Patients With Multiple Myeloma Less Than 65 Yrs Old
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Untreated
Transplant
Younger
Lead sponsor: PETHEMA Foundation
Sponsor class: OTHER
First posted: 2007-04-18
Enrollment: 390
Sex: ALL
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is to compare safety and efficacy of three induction treatments: VBMCP-VBAD / Velcade versus Thalidomide / Dexamethasone versus Velcade / Thalidomide / Dexamethasone. The second one is to evaluate the ability of stem cell mobilization after the treatments in order to do an autologous transplant. Otherwise this study wants to compare the safety and efficacy of the maintenance treatments: Interferón a-2b versus Thalidomide versus Thalidomide/Velcade.

Detailed description: A total of up to 390 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 (1:1:1) to receive VBMCP-VBAD+Velcade (Group A) or Thalidomide+Dexamethasone (Group B) or Thalidomide+Dexamethasone+Velcade (Group C). All of them will received the induction treatment up to 24 weeks.

After 4 weeks, without progression or unacceptable toxicity, There will be stem cell mobilization to do an autologous transplant. Three months after transplant, patients will be again randomized (1:1:1) to receive maintenance treatment: Interferon-a (Group M1) or Thalidomide (Group M2) or Thalidomide+Velcade (Group M3) 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 criteria: Inclusion Criteria:

1. Must be able to comply with the protocol requirements
2. Must voluntary sign the informed consent before performance of any study-related procedure not part of normal medical care,
3. Age \<65 years and possibly to do an autologous transplant.
4. Patient recently diagnosed with symptomatic Multiple Myeloma who has not received any previous chemotherapy treatment for Multiple Myeloma.
5. Patient has a measurable disease defined as quantifiable serum monoclonal protein value and, where applicable, urine Light-chain excretion of ≥ 200 mg/24 hours.
6. ECOG \< 2.
7. El patient has a life-expectancy \> 3 months.
8. Patient has the following laboratory values before beginning induction treatment:

   1. 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.
   2. Corrected serum calcium \<14mg/dl.
   3. Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal.
   4. Alanine transaminase (ALT): ): ≤ 2.5 x the upper limit of normal.
   5. Total bilirubin: ≤1.5 x the upper limit of normal.
   6. Serum creatinine ≤ 2 mg/dl.
9. For Patients included in Thalidomide branches: women of childbearing age must not have sex unless they use two anticonceptive methods beginning 4 weeks before the first dose, during all the study until 4 weeks after the last one.

Exclusion Criteria:

1. Non-secretor Myeloma.
2. Patients previously received treatment to Multiple Myeloma, except steroids doses for urgency or bisphosphonates or radiotherapy before beginning treatment.
3. Patients with \< Grade 2 peripheral neuropathy within 14 days before enrolment.
4. Patient had major surgery within 4 weeks before enrolment.
5. Patient has hypersensitivity to bortezomib, boron or mannitol or Thalidomide.
6. Patient has received other investigational drugs within 30 days before enrolment.
7. Patient is known to be seropositive for the human immunodeficiency virus (HIV), Hepatitis B surface antigen-positive or active hepatitis C infection.
8. 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.
9. Patient is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.
10. Pregnancy or breast-feed women.

Primary outcomes:
measure: The primary objective is to compare safety and efficacy of three induction treatments: VBMCP-VBAD / Velcade versus Thalidomide / Dexamethasone versus Velcade / Thalidomide / Dexamethasone.
timeFrame: 2 years
Secondary outcomes:
measure: Evaluate the ability of stem cell mobilization after the treatments in order to do an autologous transplant. Otherwise this study wants to compare the safety and efficacy of the maintenance treatments: Interferón a-2b versus Thalidomide
timeFrame: 2 years
Other outcomes:
Locations:
city: Zaragoza
country: Spain
facility: Hospital Royo Villanova
state: Aragón
city: Manresa
country: Spain
facility: Xarxa assistencial de Manresa
state: Barcelona
city: Sabadell
country: Spain
facility: Corporació Sanitària Parc Taulí
state: Barcelona
city: Castello
country: Spain
facility: Hospital general de Castellón
state: Castellón
city: Pamplona
country: Spain
facility: Clínica Universitaria de Navarra
state: Navarra
city: Albacete
country: Spain
facility: Complejo Hospitalario Universitario de Albacete
city: Alcorcón
country: Spain
facility: Fundación Hospital Alcorcón
city: Alicante
country: Spain
facility: Hospital General de Alicante
city: Avila
country: Spain
facility: Hospital Ntra. Sra. Sonsoles
city: Badajoz
country: Spain
facility: Hospital Regional Universitario Infanta Cristina
city: Badalona
country: Spain
facility: Hospital de Badalona Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Vall D'Hebron
city: Bilbao
country: Spain
facility: Basurtuko Ospitalea
city: Bilbao
country: Spain
facility: Hospital de Cruces
city: Ciudad Real
country: Spain
facility: Hospital Nuestra Señora de Alarcos
city: Cuenca
country: Spain
facility: Hospital Virgen de la Luz
city: Cáceres
country: Spain
facility: Hospital Virgen del Puerto
city: Donostia
country: Spain
facility: Hospital Donostia
city: Elda
country: Spain
facility: Hospital General de Elda
city: Getafe
country: Spain
facility: Hospital Universitario de Getafe
city: Guadalajara
country: Spain
facility: Hospital General de Guadalajara
city: Huesca
country: Spain
facility: Hospital de San Jorge
city: Lanzarote
country: Spain
facility: Hospital General de Lanzarote
city: Leon
country: Spain
facility: Complejo Hospitalario León
city: Lugo
country: Spain
facility: Complexo Hospitalario Xeral-Calde
city: Madrid
country: Spain
facility: Clínica Moncloa
city: Madrid
country: Spain
facility: Clínica Puerta de Hierro
city: Madrid
country: Spain
facility: Clínica Rúber
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Central de la Defensa
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos de Madrid
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Martorell
country: Spain
facility: Fundación Hospital Sant Joan de Déu de Martorell
city: Murcia
country: Spain
facility: Hospital General Morales Meseguer
city: Murcia
country: Spain
facility: Hospital Santa María del Rosell
city: Murcia
country: Spain
facility: Hospital Virgen del Castillo de Yecla
city: Mérida
country: Spain
facility: Hospital de Mérida
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Palencia
country: Spain
facility: Hospital del Río Carrión
city: Palma de Gran Canaria
country: Spain
facility: Hospital de Gran Canaria Doctor Negrín
city: Palma de Mallorca
country: Spain
facility: Complejo Asistencial Son Dureta
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer
city: Palma de Mallorca
country: Spain
facility: Hospital Verge del Toro
city: Pamplona
country: Spain
facility: Hospital de Navarra
city: Pamplona
country: Spain
facility: Hospital Virgen del Camino
city: Pontevedra
country: Spain
facility: Complejo Hospitalario de Pontevedra_Hospital Montecelo
city: Pontevedra
country: Spain
facility: Complejo Hospitalario de Pontevedra_Hospital Provincial
city: Sagunto
country: Spain
facility: Hospital de Sagunto
city: Salamanca
country: Spain
facility: Hospital Clínico de Salamanca
city: San Pedro de Alcántara
country: Spain
facility: Hospital San Pedro de Alcántara
city: Sant Pere de Ribes
country: Spain
facility: Clínica Sant Camil
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
city: Segovia
country: Spain
facility: Hospital General de Segovia
city: Tarragona
country: Spain
facility: Hospital Joan XXIII
city: Tenerife
country: Spain
facility: Hospital Universitario de Canarias
city: Toledo
country: Spain
facility: Hospital Nuestra Señora del Prado
city: Toledo
country: Spain
facility: Hospital Virgen de la Salud
city: Valencia
country: Spain
facility: Fundación Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova
city: Valencia
country: Spain
facility: Hospital Clínic
city: Valencia
country: Spain
facility: Hospital Dr. Peset
city: Valencia
country: Spain
facility: Hospital Francesc de Borja
city: Valencia
country: Spain
facility: Hospital General Básico de la Defensa
city: Valencia
country: Spain
facility: Hospital La Fe
city: Valladolid
country: Spain
facility: Hospital Clínico de Valladolid
city: Vigo
country: Spain
facility: Complejo Hospitalario Universitario de Vigo
city: Vinaros
country: Spain
facility: Comarcal de Vinaros
city: Vitoria
country: Spain
facility: Hospital Txagorritxu
city: Vizcaya
country: Spain
facility: Hospital de Galdakao
city: Zamora
country: Spain
facility: Hospital Virgen de la Concha
city: Zaragoza
country: Spain
facility: Hospital Clínico Lozano Blesa
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Bladé Joan, Dr
role: PRINCIPAL_INVESTIGATOR
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