Efficacy/Safety Study of R-CHOP vs Bortezomib-R-CAP for Young Patients With Diffuse Large B-cell Lymphoma With Poor IPI.

NCT ID: NCT01848132

Last Updated: 2018-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 121 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-03
• Study Completion Date: 2018-08-31

Brief Summary

Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma, accounting for between 30% and 50% of the patients. Although it is considered a curable disease, still at least 40 % of the patients will fail first line chemotherapy. The International Prognostic Index (IPI) score and the age adjusted IPI (aIPI) has been used since they were published to identify patients with different outcome.

There is not standard therapy for young patients with DLBCL and unfavourable IPI score. The survival of these patients remains poor, with EFS around 40%.

The combination of RCHOP with new drugs is an attractive approach to treat these patients.

The goal is to evaluate the proportion of patients with Event-Free Survival (EFS) after 2 years, with a diagnosis of DLBCL with an aIPI > 1 or an aIPI =1 with increased levels of beta-2-microglobulin (above the Upper Limits of Normal.)

Detailed Description

Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma, accounting for between 30% and 50% of the patients. Although it is considered a curable disease, still at least 40 % of the patients will fail first line chemotherapy. The International Prognostic Index (IPI) score and the age adjusted IPI (aIPI) has been used since they were published to identify patients with different outcome.

CHOP chemotherapy administered every 21 days has been for years the standard therapy for advanced DLBCL achieving a long term overall survival (OS) of about 40%. Many studies show that the addition of the monoclonal antibody Rituximab improves the patients survival achieving higher rates of event-free survival in elderly patients with both,favourable and unfavourable IPI score. R-CHOP also improved survival in young patients with favourable IPI score.

There is not standard therapy for young patients with DLBCL and unfavourable IPI score. The survival of these patients remains poor, with EFS around 40%.

The combination of RCHOP with new drugs is an attractive approach to treat these patients.

The investigators propose a phase II randomized clinical trial for young patients with unfavourable IPI score DLBCL using 6 cycles of the combination of subcutaneous Bortezomib with R-CAP (RCHOP without vincristine, to avoid neuropathy) comparing with the standard immunochemotherapy regimen R- CHOP every 21 days.

The goal is to evaluate the proportion of patients with Event-Free Survival (EFS) after 2 years, with a diagnosis of DLBCL with aIPI > 1 or aIPI =1 with increased levels of beta-2-microglobulin (above the Upper Limits of Normal).

Conditions

Diffuse, Large B-Cell, Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

R-CHOP

6 cycles every 21 days.

• Rituximab: intravenous, 375 mg/m2, day 1
• Cyclophosphamide: intravenous, 750 mg/m2, day 1
• Doxorubicin: intravenous, 50 mg/m2, day 1
• Vincristine: intravenous, 1,4 mg/m2, day 1
• Prednisone: oral, 100 mg, days 1-5

Group Type: ACTIVE_COMPARATOR

Rituximab

Intervention Type: DRUG

Rituximab: intravenous, 375 mg/m2, day 1

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide: intravenous, 750 mg/m2, day 1

Doxorubicin

Intervention Type: DRUG

Adriamycin:intravenous, 50 mg/m2, day 1

Prednisone

Intervention Type: DRUG

Prednisone: oral, 100 mg, days 1-5

Vincristine

Intervention Type: DRUG

Vincristine: intravenous, 1,4 mg/m2, day 1

B-R-CAP

6 cycles every 21 days

• Bortezomib: subcutaneous, 1,3 mg/m2, day 1, 8, 15
• Rituximab: intravenous, 375 mg/m2, day 1
• Cyclophosphamide: intravenous, 750 mg/m2, day 1
• Doxorubicin: intravenous, 50 mg/m2, day 1
• Prednisone: oral, 100 mg, days 1-5

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

Bortezomib: subcutaneous, 1,3 mg/m2, day 1, 8, 15.

Rituximab

Intervention Type: DRUG

Rituximab: intravenous, 375 mg/m2, day 1

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide: intravenous, 750 mg/m2, day 1

Doxorubicin

Intervention Type: DRUG

Adriamycin:intravenous, 50 mg/m2, day 1

Prednisone

Intervention Type: DRUG

Prednisone: oral, 100 mg, days 1-5

Interventions

Bortezomib

Bortezomib: subcutaneous, 1,3 mg/m2, day 1, 8, 15.

Intervention Type: DRUG

Rituximab

Rituximab: intravenous, 375 mg/m2, day 1

Intervention Type: DRUG

Cyclophosphamide

Cyclophosphamide: intravenous, 750 mg/m2, day 1

Intervention Type: DRUG

Doxorubicin

Adriamycin:intravenous, 50 mg/m2, day 1

Intervention Type: DRUG

Prednisone

Prednisone: oral, 100 mg, days 1-5

Intervention Type: DRUG

Vincristine

Vincristine: intravenous, 1,4 mg/m2, day 1

Intervention Type: DRUG

Other Intervention Names

Velcade; Adriamycin

Eligibility Criteria

Inclusion Criteria

• Patients diagnosed with primary diffuse DLBCL who have never received treatment for this condition.
• Age between 18 and 70 years.
• Age-adjusted IPI (aIPI) higher than 1, or equal 1 with high levels of beta-2-microglobulin (above UNL)
• Cluster of Differentiation 20 (CD20) positive b lymphocytes.
• Eastern Cooperative Oncology Group (ECOG) 0-3.
• More than 12 weeks of life expectancy.
• Signed Informed Consent.
• Nor pregnant women nor breast-feeding women without heterosexual activity during the entire study. Women with heterosexual activity only if they are willing to use two methods of contraceptive. The two contraceptive methods can be, two barrier method or a barrier method combinated with an hormonal contraceptive method to prevent pregnancy, used during the entire study and until 3 months after the study completion.

Exclusion Criteria

• Pregnant women or in breast-feeding period, or adults in childbearing period not using an effective contraception method.
• Patients with Central Nervous System (CNS) lymphoma.
• Severely impaired renal function (creatinine> 2.5 UNL) or hepatic function impairment (bilirubin or Alanine Amino Transaminase (ALT) / Aspartate Aminotransferase (AST) > 3 UNL), unless it is suspected to be due to the disease.
• Human immunodeficiency virus (HIV) positive patients
• Patient previously treated for the DLBCL
• Positive determination of chronic hepatitis B (defined as positive serology for HBsAg). It will be allowed to enroll patients with hidden or previous hepatitis B (defined as positive antibodies against the core of the hepatitis B virus [HBcAb] and HBsAg negative) if undetectable Hepatitis B Virus (HBV) DNA.
• Positive results for hepatitis C (antibody serology for hepatitis C virus ((HCV)). Patients with HCV positive may only participate if the Polymerase Chain Reaction (PCR) result is negative for HCV RNA.
• History of cardiovascular disease with ventricular ejection fraction < 50%.
• Patients with severe psychiatric conditions that may interfere with their ability to understand the study (including alcoholism or drug addiction).
• Patients with known hypersensitivity to murine proteins or any other components of the study drugs.
• Transformed follicular lymphoma.
• History of other neoplastic malignancy with < 5 year of complete response (except for Squamous Cell Carcinoma of the Skin or cervical Carcinoma in situ).
• Presence of uncontrolled conditions: cardiac, respiratory, neurologic, metabolic etc., not related to lymphoma.
• Uncontrolled hypertension (diastolic blood pressure over 110 mmHg).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen-Cilag, S.A.

INDUSTRY

Sponsor Role: collaborator

Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eva González, MD

Role: STUDY_CHAIR

Institut Catalá d'Oncología, Hospital Duran i Reynals

Locations

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Aragon, Spain

Hospital Son Llàtzer

Palma, Balearic Islands, Spain

Institut Català d'Oncologia, Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Institut Català d'Oncologia, Hospital Duran i Reynals

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

Hospital de Jerez

Jerez de la Frontera, Cádiz, Spain

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, Spain

Complejo Hospitalario Universitario de Vigo

Vigo, Pontevedra, Spain

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Hospital Universitari de Girona Doctor Josep Trueta

Girona, , Spain

Hospital Universitario Infanta Leonor

Madrid, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Centro Integral Oncológico Clara Campal

Madrid, , Spain

Hospital Universitario de Salamanca

Salamanca, , Spain

Hospital Universitario de Canarias

Santa Cruz de Tenerife, , Spain

Hospital Universitario Virgen del Rocío

Seville, , Spain

Hospital Universitario Doctor Peset

Valencia, , Spain

Hospital Universitari i Politècnic La Fe

Valencia, , Spain

Countries

Spain

Other Identifiers

2012-005138-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BRCAP-GELTAMO12

Identifier Type: -

Identifier Source: org_study_id