GEM05MENOS65: GEM05 for Patients With Multiple Myeloma Under 65 Years

Sponsor

PETHEMA Foundation (Other)

Overall Status

Completed

CT.gov ID

NCT00461747

Collaborator

(none)

390

Enrollment

Locations

Arms

33.1

Duration (Months)

4.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: VBMCP/VBAD/Velcade Drug: Thalidomide/Dexamethasone Drug: Velcade/Thalidomide/Dexamethasone	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

390 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Mar 1, 2006

Actual Primary Completion Date :

Dec 1, 2008

Actual Study Completion Date :

Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A 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	Drug: 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, Melfalan, 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.
Experimental: B 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	Drug: 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
Experimental: C 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.	Drug: Velcade/Thalidomide/Dexamethasone Thalidomide: day 1 cycle 1 (50 mg/day).If toxicity is < grade 2, the dose 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

Arm

Intervention/Treatment

Active Comparator: A

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

Drug: 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, Melfalan, 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.

Experimental: B

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

Drug: 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

Experimental: C

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.

Drug: Velcade/Thalidomide/Dexamethasone

Thalidomide: day 1 cycle 1 (50 mg/day).If toxicity is < grade 2, the dose 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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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,
Age <65 years and possibly to do an autologous transplant.
Patient recently diagnosed with symptomatic Multiple Myeloma who has not received any previous chemotherapy treatment for Multiple Myeloma.
Patient has a measurable disease defined as quantifiable serum monoclonal protein value and, where applicable, urine Light-chain excretion of ≥ 200 mg/24 hours.
ECOG < 2.
El 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.
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:

Non-secretor Myeloma.
Patients previously received treatment to Multiple Myeloma, except steroids doses for urgency or bisphosphonates or radiotherapy before beginning treatment.
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 or Thalidomide.
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.
Pregnancy or breast-feed women.

Contacts and Locations

Locations

	Site	City	State	Country
1	Hospital Royo Villanova	Zaragoza	Aragón	Spain
2	Xarxa assistencial de Manresa	Manresa	Barcelona	Spain
3	Corporació Sanitària Parc Taulí	Sabadell	Barcelona	Spain
4	Hospital general de Castellón	Castello	Castellón	Spain
5	Clínica Universitaria de Navarra	Pamplona	Navarra	Spain
6	Complejo Hospitalario Universitario de Albacete	Albacete		Spain
7	Fundación Hospital Alcorcón	Alcorcón		Spain
8	Hospital General de Alicante	Alicante		Spain
9	Hospital Ntra. Sra. Sonsoles	Avila		Spain
10	Hospital Regional Universitario Infanta Cristina	Badajoz		Spain
11	Hospital de Badalona Germans Trias i Pujol	Badalona		Spain
12	Hospital Clinic i Provincial de Barcelona	Barcelona		Spain
13	Hospital de la Santa Creu i Sant Pau	Barcelona		Spain
14	Hospital del Mar	Barcelona		Spain
15	Hospital Vall D'Hebron	Barcelona		Spain
16	Basurtuko Ospitalea	Bilbao		Spain
17	Hospital de Cruces	Bilbao		Spain
18	Hospital Nuestra Señora de Alarcos	Ciudad Real		Spain
19	Hospital Virgen de la Luz	Cuenca		Spain
20	Hospital Virgen del Puerto	Cáceres		Spain
21	Hospital Donostia	Donostia		Spain
22	Hospital General de Elda	Elda		Spain
23	Hospital Universitario de Getafe	Getafe		Spain
24	Hospital General de Guadalajara	Guadalajara		Spain
25	Hospital de San Jorge	Huesca		Spain
26	Hospital General de Lanzarote	Lanzarote		Spain
27	Complejo Hospitalario León	Leon		Spain
28	Complexo Hospitalario Xeral-Calde	Lugo		Spain
29	Clínica Moncloa	Madrid		Spain
30	Clínica Puerta de Hierro	Madrid		Spain
31	Clínica Rúber	Madrid		Spain
32	Fundación Jiménez Díaz	Madrid		Spain
33	Hospital 12 de Octubre	Madrid		Spain
34	Hospital Central de la Defensa	Madrid		Spain
35	Hospital Clínico San Carlos de Madrid	Madrid		Spain
36	Hospital Ramón y Cajal	Madrid		Spain
37	Hospital Universitario de la Princesa	Madrid		Spain
38	Hospital Universitario La Paz	Madrid		Spain
39	Fundación Hospital Sant Joan de Déu de Martorell	Martorell		Spain
40	Hospital General Morales Meseguer	Murcia		Spain
41	Hospital Santa María del Rosell	Murcia		Spain
42	Hospital Virgen del Castillo de Yecla	Murcia		Spain
43	Hospital de Mérida	Mérida		Spain
44	Hospital Central de Asturias	Oviedo		Spain
45	Hospital del Río Carrión	Palencia		Spain
46	Hospital de Gran Canaria Doctor Negrín	Palma de Gran Canaria		Spain
47	Complejo Asistencial Son Dureta	Palma de Mallorca		Spain
48	Hospital Son Llatzer	Palma de Mallorca		Spain
49	Hospital Verge del Toro	Palma de Mallorca		Spain
50	Hospital de Navarra	Pamplona		Spain
51	Hospital Virgen del Camino	Pamplona		Spain
52	Complejo Hospitalario de Pontevedra_Hospital Montecelo	Pontevedra		Spain
53	Complejo Hospitalario de Pontevedra_Hospital Provincial	Pontevedra		Spain
54	Hospital de Sagunto	Sagunto		Spain
55	Hospital Clínico de Salamanca	Salamanca		Spain
56	Hospital San Pedro de Alcántara	San Pedro de Alcántara		Spain
57	Clínica Sant Camil	Sant Pere de Ribes		Spain
58	Hospital Universitario Marqués de Valdecilla	Santander		Spain
59	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela		Spain
60	Hospital General de Segovia	Segovia		Spain
61	Hospital Joan XXIII	Tarragona		Spain
62	Hospital Universitario de Canarias	Tenerife		Spain
63	Hospital Nuestra Señora del Prado	Toledo		Spain
64	Hospital Virgen de la Salud	Toledo		Spain
65	Fundación Instituto Valenciano de Oncología	Valencia		Spain
66	Hospital Arnau de Vilanova	Valencia		Spain
67	Hospital Clínic	Valencia		Spain
68	Hospital Dr. Peset	Valencia		Spain
69	Hospital Francesc de Borja	Valencia		Spain
70	Hospital General Básico de la Defensa	Valencia		Spain
71	Hospital La Fe	Valencia		Spain
72	Hospital Clínico de Valladolid	Valladolid		Spain
73	Complejo Hospitalario Universitario de Vigo	Vigo		Spain
74	Comarcal de Vinaros	Vinaros		Spain
75	Hospital Txagorritxu	Vitoria		Spain
76	Hospital de Galdakao	Vizcaya		Spain
77	Hospital Virgen de la Concha	Zamora		Spain
78	Hospital Clínico Lozano Blesa	Zaragoza		Spain
79	Hospital Miguel Servet	Zaragoza		Spain