Study of Treatment for Newly Diagnosed Multiple Myeloma Patients Older Than 65 Years With Sequential Melphalan/Prednisone/Velcade (MPV) Followed by Revlimid/Low Dose Dexamethasone (Rd) Versus Alternating Velcade/Melphalan/Prednisone (MPV) With Revlimid/Low Dose Dexamethasone

Multiple Myeloma Clinical Trial

Official title:

A National, Open-label, Multicenter, Randomized, Comparative Phase IIb Study of Treatment for Newly Diagnosed Multiple Myeloma Patients Older Than 65 Years With Sequential Melphalan/Prednisone/Velcade (MPV) Followed by Revlimid/Low Dose Dexamethasone (Rd) Versus Alternating Velcade/Melphalan/Prednisone (MPV) With Revlimid/Low Dose Dexamethasone (Rd).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01237249
• Other study ID #: GEM2010MAS65
• Status: Completed
• Phase: Phase 2
• First received: November 4, 2010
• Last updated: January 16, 2017
• Start date: February 2011
• Est. completion date: May 2016

Study information

• Verified date: January 2017
• Source: PETHEMA Foundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a national, multicenter, open-label, randomized, comparative study designed to compare, first, the TTP of the two treatment schemes proposed (MPV followed by Rd or MPV alternating with Rd) in newly diagnosed MM patients older than 65 years. This comparison will be performing in terms of both efficacy and safety. Up to 120 patients will be included in each treatment arm and evaluated at scheduled visits in up to 3 study periods: Pre-treatment, Treatment and Follow-up.

Primary outcome measure:

• To evaluate the efficacy in terms of time to progression (TTP) at 18 months of MPV and Rd used as either in a sequential or alternating approach in newly diagnosed MM patients older than 65 years.

• To evaluate the toxicity (safety and tolerability) of the sequential versus the alternating use of MPV and Rd.

Secondary outcome measure:

• To evaluate the response, duration of response, progression free survival (PFS), time to next therapy (TNT) and overall survival (OS) in the two different groups of patients.

• To identify, within the group of patients treated with the alternating scheme, the biological characteristics (including a comprehensive genomic analysis) of those patients resistant to one or the other, and patients refractory to both treatments

Description:

The Pre-treatment period includes Screening visit. After providing written informed consent form to participate in the study, patients will be evaluated for eligibility during a screening period of 14 days (Days -14 to -1). If patients meet all inclusion and exclusion criteria will be randomized at the moment of entry in the trial in a 1:1 allocation to receive either MPV followed by Rd (Treatment Group A) or MPV alternating with Rd (Treatment Group B).

Patients in the Treatment Group A will receive nine cycles of MPV consisting on one 6-weeks cycle of Velcade (Bortezomib) as an intravenous bolus twice weekly (days 1, 4, 8, 11, 22, 25, 29 and 32) followed by a 10 day rest period (day 33 to 42), in combination with oral Melphalan, once daily on days 1 to 4 and oral Prednisone, once daily on days 1 to 4, followed by eight 4-weeks cycles of Velcade (Bortezomib) as an intravenous bolus on days 1, 8, 15 and 22 followed by a 6 day rest period (days 23 to 28), in combination with Melphalan and Prednisone per os once daily on days 1 to 4, followed by a 24-day rest period (days 5 to 28). After the nine MPV cycles, patients will receive nine cycles of Rd consisting on 4-weeks cycles, including Revlimid (lenalidomide), once daily on days 1-21 followed by a 7 day rest period (days 22 to 28) plus oral dexamethasone, once weekly on days 1,8,15 and 22, followed by a 6 day rest period (days 23 to 28).

Patients in the Treatment Group B will receive the same schedule of therapy, but the MPV cycles will be alternated with Rd cycles. In this treatment Group B, patients will be again randomized to start receiving either MPV or Rd as first cycle of therapy. Overall, patients will receive an identical number of cycles, nine cycles of MPV and nine of Rd. Patients randomized to Treatment Group A relapsing/progressing or with major toxicities under treatment with MPV will be crossover to receive Rd, but only after study coordinator approval.

During the Treatment Period, patients will be evaluated at day 1 of each cycle. After completion of the Treatment Period, all patients will be evaluated every 2 months thereafter.

Safety will be assessed by the monitoring of adverse events, physical examinations, vital signs measurements, and haematology and clinical chemistry test. Response to treatment will be based on EBMT an IMWG criteria. Response to treatment will be evaluated at day 1 of each induction cycle, and every 2 months during thereafter.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 250
• Est. completion date: May 2016
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

1. Written informed consent obtained before starting any study-specific procedure.

2. Symptomatic elderly MM newly diagnosed by EBMT criteria older than 65 years.

3. Performance status (ECOG) = 2.

4. Have pre-treatment clinical laboratory values meeting the following criteria within 14 days of randomization:

• platelet count = 75x109/L

• haemoglobin = 8g/dL

• absolute neutrophil count (ANC) = 1.0x109/L

• Serum bilirubin = 1.5 mg/dL and alkaline phosphatise = 2.5 x ULN AST, ALT = 2.5 x ULN

• Serum creatinine =2,5 mg/dl

Exclusion Criteria:

1. Patient previously received treatment with Velcade or Revlimid.

2. Patient previously received treatment for Multiple Myeloma.

3. Patient has = Grade 2 peripheral neuropathy within 14 days before enrolment.

4. Patient has hypersensitivity to bortezomib, boron, mannitol or lenalidomide.

5. Patient has received other investigational drugs with 28 days before enrolment.

6. Patient had a myocardial infarction within 6 months of enrolment 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.

7. Patient currently is enrolled in another clinical research study and/or is receiving an investigational agent for any reason.

8. Radiation therapy within 30 days before randomization, at least patient has had antialgic radiation. Radiation therapy will be afterwards permitted during the treatment period if it is indicated due to the presence of plasmacytomas

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Melphalan

• Prednisone

• Velcade

• Revlimid

• Dexamethasone

Locations

Country	Name	City	State
Spain	Hospital Principe de Asturias	Alcalá de Henares	Madrid
Spain	Fundación Hospital Alcorcón	Alcorcón
Spain	Hospital de Badalona Germans Trias i Pujol	Badalona
Spain	H. Vall d'Hebron, Barcelona	Barcelona
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	ICO - Duran i Reynals, Hospitalet de Llobregat	Barcelona
Spain	Hospital de Cruces	Bilbao
Spain	Complejo Hospitalario de Cáceres	Cáceres
Spain	Hospital Puerta del Mar	Cádiz
Spain	Hospital General de Castellón	Castellón
Spain	Hospital General	Ciudad Real
Spain	Hospital Virgen de la Luz	Cuenca
Spain	Hospital Donostia	Donostia
Spain	Hospital Francesc Borja	Gandía
Spain	ICO - Josep Trueta	Girona
Spain	Hospital General de Guadalajara	Guadalajara
Spain	H. de Jerez	Jerez de la Frontera
Spain	Complejo Hospitalario León	Leon
Spain	Clínica Puerta de Hierro	Madrid
Spain	Hospital 12 de Octubre. Madrid	Madrid
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital de Fuenlabrada	Madrid
Spain	Hospital de la Princesa	Madrid
Spain	Hospital de Madrid, S.A.- Norte Hospital General	Madrid
Spain	Hospital del Tajo	Madrid
Spain	Hospital Infanta Leonor	Madrid
Spain	Hospital Infanta Sofia	Madrid
Spain	Hospital la Paz	Madrid
Spain	Hospital Ramón y Cajal	Madrid
Spain	Hospital Severo Ochoa	Madrid
Spain	Hospital Universitario Gregorio Marañón	Madrid
Spain	MD Anderson	Madrid
Spain	Complejo Hospital Costa del Sol	Málaga
Spain	Hospital Nuestra Señora de Valme	Málaga
Spain	Althaia	Manresa
Spain	Hospital General Univeristario Morales Messeguer	Murcia
Spain	Hospital Virgen de la Arrixaca	Murcia
Spain	Hospital de la Diputación de Navarra	Navarra
Spain	Hospital de Gran Canaria Doctor Negrín	Palma de Gran Canaria
Spain	Complejo Asistencial Son Dureta	Palma de Mallorca
Spain	H. Son Llatzer	Palma de Mallorca	Baleares
Spain	Clínica Universitaria de Navarra	Pamplona	Navarra
Spain	Hospital Virgen del Camino	Pamplona
Spain	Corporació Sanitaria Parc Taulí	Sabadell
Spain	Hospital Clínico de Salamanca	Salamanca
Spain	Hoaspital Marqués de Valdecilla	Santander
Spain	Complejo Hospitalario Universitario de Santiago	Santiago de Compostela
Spain	Hospital General de Segovia	Segovia
Spain	Complejo Hospitalario Regional Virgen del Rocío	Sevilla
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	Hospital Arnau de Vilanova	Valencia
Spain	Hospital Clínico de Valencia.	Valencia
Spain	Hospital La Fe	Valencia
Spain	Hospital Universitario Dr. Peset	Valencia
Spain	Hospital Txagorritxu	Vitoria
Spain	Hospital Virgen de la Concha	Zamora
Spain	Hospital Clinico Lozano Blesa	Zaragoza
Spain	Miguel Servet	Zaragoza

Sponsors (4)

Lead Sponsor	Collaborator
PETHEMA Foundation	Celgene, Janssen-Cilag Ltd., TFS Trial Form Support

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the efficacy in terms of time to progression (TTP) at 18 months of MPV and Rd used as either in a sequential or alternating approach in newly diagnosed MM patients older than 65 years.		18 months
Primary	To evaluate the toxicity (safety and tolerability) of the sequential versus the alternating use of MPV and Rd,in terms of adverse events presented in both groups of patients		6 months
Secondary	To evaluate the response in both groups of patients		1 year
Secondary	To identify, within the group of patients treated with the alternating scheme, the biological characteristics (including a comprehensive genomic analysis) of those patients resistant to one or the other, and patients refractory to both treatments		2 years
Secondary	Duration of response in two groups of patients		2 years
Secondary	Progression free survival (PFS) in two different groups of patients		18 months
Secondary	Time to next therapy (TNT)		2 years
Secondary	Overall survival (OS) in the two different groups of patients		5 years

External Links

•   Spanish Association of Hematology