GEM05 for Patients With Multiple Myeloma Under 65 Years

Phase 3

Completed

• Conditions: Multiple Myeloma
• Interventions: Drug: VBMCP/VBAD/Velcade; Drug: Thalidomide/Dexamethasone; Drug: Velcade/Thalidomide/Dexamethasone

• Registration Number: NCT00461747
• Lead Sponsor: PETHEMA Foundation

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.

Study Timeline

• Study Start: 2006-03
• Study First Submitted: 2007-04-17
• Study First Submitted QC: 2007-04-17
• Study First Posted: 2007-04-18
• Primary Completion: 2008-12
• Study Completion: 2008-12
• Status Verified: 2009-09
• Last Update Submitted: 2009-09-17
• Last Update Posted: 2009-09-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 390

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	VBMCP/VBAD/Velcade	Four alternating cycles of VBMCP/VBAD + Velcade VBMCP: Vincristine, 0,03 mg/Kg (iv) day 1, BCNU, 0,5 mg/Kg iv day 1, Cyclophosphamide, 10 mg/Kg iv day 1, Melfalán, 0,25 mg/Kg oral days 1 to 4 Prednisone, 1 mg/Kg oral days 1 to 4; 0,5 mg/Kg oral days 5 to 8 and 0,25 mg/Kg oral days 9 to 12. VBAD : Vincristine, 1mg via iv day 1, BCNU, 30 mg/m2 iv day 1, Adriamycine, 40mg/m2 iv day 1 Dexamethasone, 40 mg oral days 1 to 4, 9 to 12 and 17 to 20. The interval between VBMCP and VBAD is 5 weeks and between VBAD and VBMCP is 4 weeks. The patients will received two cycles of VBMCP and two cycles of VBAD. After 4 weeks of last cycle of VBAD, patients will received two cycles of Velcade, 1,3 mg/ m2 iv twice a week (days 1, 4, 8 and 11), followed by 10 days without treatment
B	Thalidomide/Dexamethasone	Six cycles of 4 weeks of Thalidomide/Dexamethasone. Thalidomide day 1, cycle 1 (50 mg/day v.o). If toxicity \< grade 2, dose will be 100 mg/day on day 15, cycle 1 and 200 mg/day on day 1, cycle 2. Dexamethasone:40 mg/day v.o.days 1 to 4 and 9 to 12, with a period without treatment of 16 days
C	Velcade/Thalidomide/Dexamethasone	Thalidomide: day 1 cycle 1 (50 mg/day).If toxicity is \< grade 2, the dose will be increased (100 mg/day) at day 15 cycle 1 and (200 mg de Thalidomide) at day 1 cycle 2. Dexamethasone: 40 mg/day v.o days 1 to 4 and 8 to 11, with a period without treatment of 17 days. Velcade: 1,3 mg/m2 iv twice a week (days 1, 4, 8 and 11) with a period without treatment of 17 days.

Primary Outcome Measures

Name	Time	Method
The primary objective is to compare safety and efficacy of three induction treatments: VBMCP-VBAD / Velcade versus Thalidomide / Dexamethasone versus Velcade / Thalidomide / Dexamethasone.	2 years

Secondary Outcome Measures

Name	Time	Method
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	2 years

Trial Locations

Locations (79)

Hospital general de Castellón; 🇪🇸 Castello, Castellón, Spain

Fundación Hospital Alcorcón; 🇪🇸 Alcorcón, Spain

Hospital Ntra. Sra. Sonsoles; 🇪🇸 Avila, Spain

Hospital Regional Universitario Infanta Cristina; 🇪🇸 Badajoz, Spain

Hospital General de Alicante; 🇪🇸 Alicante, Spain

Hospital de Badalona Germans Trias i Pujol; 🇪🇸 Badalona, Spain

Hospital de Galdakao; 🇪🇸 Vizcaya, Spain

Hospital General de Elda; 🇪🇸 Elda, Spain

Hospital General Morales Meseguer; 🇪🇸 Murcia, Spain

Hospital Central de la Defensa; 🇪🇸 Madrid, Spain

Hospital Clínico San Carlos de Madrid; 🇪🇸 Madrid, Spain

Hospital Ramón y Cajal; 🇪🇸 Madrid, Spain

Hospital Santa María del Rosell; 🇪🇸 Murcia, Spain

Fundación Hospital Sant Joan de Déu de Martorell; 🇪🇸 Martorell, Spain

Hospital Son Llatzer; 🇪🇸 Palma de Mallorca, Spain

Hospital Verge del Toro; 🇪🇸 Palma de Mallorca, Spain

Hospital de Navarra; 🇪🇸 Pamplona, Spain

Hospital Virgen del Camino; 🇪🇸 Pamplona, Spain

Hospital General de Segovia; 🇪🇸 Segovia, Spain

Clínica Sant Camil; 🇪🇸 Sant Pere de Ribes, Spain

Hospital Universitario Marqués de Valdecilla; 🇪🇸 Santander, Spain

Hospital Joan XXIII; 🇪🇸 Tarragona, Spain

Hospital Nuestra Señora del Prado; 🇪🇸 Toledo, Spain

Hospital Universitario de Canarias; 🇪🇸 Tenerife, Spain

Hospital Arnau de Vilanova; 🇪🇸 Valencia, Spain

Hospital Clínico Lozano Blesa; 🇪🇸 Zaragoza, Spain

Hospital Clinic i Provincial de Barcelona; 🇪🇸 Barcelona, Spain

Basurtuko Ospitalea; 🇪🇸 Bilbao, Spain

Hospital Royo Villanova; 🇪🇸 Zaragoza, Aragón, Spain

Xarxa assistencial de Manresa; 🇪🇸 Manresa, Barcelona, Spain

Corporació Sanitària Parc Taulí; 🇪🇸 Sabadell, Barcelona, Spain

Complejo Hospitalario Universitario de Albacete; 🇪🇸 Albacete, Spain

Clínica Universitaria de Navarra; 🇪🇸 Pamplona, Navarra, Spain

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Hospital del Mar; 🇪🇸 Barcelona, Spain

Hospital Nuestra Señora de Alarcos; 🇪🇸 Ciudad Real, Spain

Hospital de Cruces; 🇪🇸 Bilbao, Spain

Hospital Virgen de la Luz; 🇪🇸 Cuenca, Spain

Hospital Donostia; 🇪🇸 Donostia, Spain

Hospital Vall D'Hebron; 🇪🇸 Barcelona, Spain

Hospital Universitario de Getafe; 🇪🇸 Getafe, Spain

Hospital General de Guadalajara; 🇪🇸 Guadalajara, Spain

Hospital Virgen del Puerto; 🇪🇸 Cáceres, Spain

Hospital Dr. Peset; 🇪🇸 Valencia, Spain

Hospital General de Lanzarote; 🇪🇸 Lanzarote, Spain

Hospital de San Jorge; 🇪🇸 Huesca, Spain

Clínica Moncloa; 🇪🇸 Madrid, Spain

Fundación Jiménez Díaz; 🇪🇸 Madrid, Spain

Complexo Hospitalario Xeral-Calde; 🇪🇸 Lugo, Spain

Clínica Rúber; 🇪🇸 Madrid, Spain

Complejo Hospitalario León; 🇪🇸 Leon, Spain

Clínica Puerta de Hierro; 🇪🇸 Madrid, Spain

Hospital La Fe; 🇪🇸 Valencia, Spain

Fundación Instituto Valenciano de Oncología; 🇪🇸 Valencia, Spain

Hospital 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Virgen de la Salud; 🇪🇸 Toledo, Spain

Hospital de Mérida; 🇪🇸 Mérida, Spain

Hospital Virgen del Castillo de Yecla; 🇪🇸 Murcia, Spain

Hospital Central de Asturias; 🇪🇸 Oviedo, Spain

Hospital del Río Carrión; 🇪🇸 Palencia, Spain

Complejo Asistencial Son Dureta; 🇪🇸 Palma de Mallorca, Spain

Hospital San Pedro de Alcántara; 🇪🇸 San Pedro de Alcántara, Spain

Hospital Clínico de Salamanca; 🇪🇸 Salamanca, Spain

Complejo Hospitalario de Pontevedra_Hospital Montecelo; 🇪🇸 Pontevedra, Spain

Hospital de Sagunto; 🇪🇸 Sagunto, Spain

Complejo Hospitalario Universitario de Santiago; 🇪🇸 Santiago de Compostela, Spain

Hospital de Gran Canaria Doctor Negrín; 🇪🇸 Palma de Gran Canaria, Spain

Complejo Hospitalario de Pontevedra_Hospital Provincial; 🇪🇸 Pontevedra, Spain

Hospital Clínic; 🇪🇸 Valencia, Spain

Hospital Francesc de Borja; 🇪🇸 Valencia, Spain

Hospital General Básico de la Defensa; 🇪🇸 Valencia, Spain

Hospital Clínico de Valladolid; 🇪🇸 Valladolid, Spain

Complejo Hospitalario Universitario de Vigo; 🇪🇸 Vigo, Spain

Hospital Virgen de la Concha; 🇪🇸 Zamora, Spain

Comarcal de Vinaros; 🇪🇸 Vinaros, Spain

Hospital Txagorritxu; 🇪🇸 Vitoria, Spain

Hospital Miguel Servet; 🇪🇸 Zaragoza, Spain

Hospital Universitario de la Princesa; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain