GEM05 for Patients With Multiple Myeloma Under 65 Years

Multiple Myeloma Clinical Trial

— GEM05MENOS65  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00461747
• Other study ID #: 2005-001110-41
• Status: Completed
• Phase: Phase 3
• First received: April 17, 2007
• Last updated: September 17, 2009
• Start date: March 2006
• Est. completion date: December 2008

Study information

• Verified date: September 2009
• Source: PETHEMA Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain:Spanish Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 390
• Est. completion date: December 2008
• Est. primary completion date: December 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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.
• 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
• 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

Locations

Country	Name	City	State
Spain	Complejo Hospitalario Universitario de Albacete	Albacete
Spain	Fundación Hospital Alcorcón	Alcorcón
Spain	Hospital General de Alicante	Alicante
Spain	Hospital Ntra. Sra. Sonsoles	Avila
Spain	Hospital Regional Universitario Infanta Cristina	Badajoz
Spain	Hospital de Badalona Germans Trias i Pujol	Badalona
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Vall D'Hebron	Barcelona
Spain	Basurtuko Ospitalea	Bilbao
Spain	Hospital de Cruces	Bilbao
Spain	Hospital Virgen del Puerto	Cáceres
Spain	Hospital general de Castellón	Castello	Castellón
Spain	Hospital Nuestra Señora de Alarcos	Ciudad Real
Spain	Hospital Virgen de la Luz	Cuenca
Spain	Hospital Donostia	Donostia
Spain	Hospital General de Elda	Elda
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 León	Leon
Spain	Complexo Hospitalario Xeral-Calde	Lugo
Spain	Clínica Moncloa	Madrid
Spain	Clínica Puerta de Hierro	Madrid
Spain	Clínica Rúber	Madrid
Spain	Fundación Jiménez Díaz	Madrid
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Central de la Defensa	Madrid
Spain	Hospital Clínico San Carlos de Madrid	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Universitario de la Princesa	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Xarxa assistencial de Manresa	Manresa	Barcelona
Spain	Fundación Hospital Sant Joan de Déu de Martorell	Martorell
Spain	Hospital de Mérida	Mérida
Spain	Hospital General Morales Meseguer	Murcia
Spain	Hospital Santa María del Rosell	Murcia
Spain	Hospital Virgen del Castillo de Yecla	Murcia
Spain	Hospital Central de Asturias	Oviedo
Spain	Hospital del Río Carrión	Palencia
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	Navarra
Spain	Hospital de Navarra	Pamplona
Spain	Hospital Virgen del Camino	Pamplona
Spain	Complejo Hospitalario de Pontevedra_Hospital Montecelo	Pontevedra
Spain	Complejo Hospitalario de Pontevedra_Hospital Provincial	Pontevedra
Spain	Corporació Sanitària Parc Taulí	Sabadell	Barcelona
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 Clínic	Valencia
Spain	Hospital Dr. Peset	Valencia
Spain	Hospital Francesc de Borja	Valencia
Spain	Hospital General Básico de la Defensa	Valencia
Spain	Hospital La Fe	Valencia
Spain	Hospital Clínico de Valladolid	Valladolid
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 Lozano Blesa	Zaragoza
Spain	Hospital Miguel Servet	Zaragoza
Spain	Hospital Royo Villanova	Zaragoza	Aragón

Sponsors (1)

Lead Sponsor	Collaborator
PETHEMA Foundation

Country where clinical trial is conducted

Spain, 

References & Publications (53)

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Jagannath S, Barlogie B, Berenson J, Siegel D, Irwin D, Richardson PG, Niesvizky R, Alexanian R, Limentani SA, Alsina M, Adams J, Kauffman M, Esseltine DL, Schenkein DP, Anderson KC. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol. 2004 Oct;127(2):165-72. — View Citation

Lahuerta JJ, Martinez-Lopez J, Serna JD, Bladé J, Grande C, Alegre A, Vazquez L, García-Laraña J, Sureda A, Rubia JD, Conde E, Martinez R, Perez-Equiza K, Moraleda JM, León A, Besalduch J, Cabrera R, Miguel JD, Morales A, García-Ruíz JC, Diaz-Mediavilla J, San-Miguel J. Remission status defined by immunofixation vs. electrophoresis after autologous transplantation has a major impact on the outcome of multiple myeloma patients. Br J Haematol. 2000 May;109(2):438-46. — View Citation

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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. — View Citation

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Samson D, Gaminara E, Newland A, Van de Pette J, Kearney J, McCarthy D, Joyner M, Aston L, Mitchell T, Hamon M, et al. Infusion of vincristine and doxorubicin with oral dexamethasone as first-line therapy for multiple myeloma. Lancet. 1989 Oct 14;2(8668):882-5. — View Citation

Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeddis J, Barlogie B. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999 Nov 18;341(21):1565-71. Erratum in: N Engl J Med 2000 Feb 3;342(5):364. — View Citation

Vesole DH, Barlogie B, Jagannath S, Cheson B, Tricot G, Alexanian R, Crowley J. High-dose therapy for refractory multiple myeloma: improved prognosis with better supportive care and double transplants. Blood. 1994 Aug 1;84(3):950-6. — View Citation

Vesole DH, Tricot G, Jagannath S, Desikan KR, Siegel D, Bracy D, Miller L, Cheson B, Crowley J, Barlogie B. Autotransplants in multiple myeloma: what have we learned? Blood. 1996 Aug 1;88(3):838-47. — View Citation

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* Note: There are 53 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes

External Links

•   Pethema Foundation web
•   Spanish association of Haematology