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

NCT01848132 | Completed Phase 2

• 2 other identifiers: BRCAP-GELTAMO122012-005138-12
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 21

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.)

Conditions

Diffuse, Large B-Cell, Lymphoma

Keywords

Lymphoma; Large B-Cell

Outcome Measures

Primary Outcomes (1)

• Proportion of patients with Event-Free Survival at 2 years.

  To evaluate the proportion of patients with event-free survival at 2 years in patients diagnosed of DLBCL with aIPI \> 1 or aIPI=1 with elevated levels of beta 2-microglobulin (above UNL). UNL= Upper Normal Limit.

  During treatment period, there will be assessments every 2 cycles. After end of treatment every 3 month the first year, every 6 months the second year and annually from 3rd to 5th year

Secondary Outcomes (6)

• Event-Free survival at 2 years in the different subtypes of DLBCL

  Once the treatment is started, there will be weekly safety visits, visits before each treatment cycle, at day 60 after the sixth cycle and then follow-up visits every three months during the first 2 years and every 6 months until the 5th year

• Overall survival at 2 years

  Once the treatment is started, there will be weekly safety visits, visits before each treatment cycle, at day 60 after the sixth cycle and then follow-up visits every three months during the first 2 years and every 6 months until the 5th year.

• Overall response rate and complete remissions

  Once the treatment is started, there will be weekly safety visits, visits before each treatment cycle, at day 60 after the sixth cycle and then follow-up visits every three months during the first 2 years and every 6 months until the 5th year.

• Toxicity according to the CTC criteria

  Once the treatment is started, there will be weekly safety visits, visits before each treatment cycle, at day 60 after the sixth cycle and then follow-up visits every three months during the first 2 years and every 6 months until the 5th year.

• To evaluate the predictive value for EFS of interim PET/CT evaluation

  Before treatment, after second cycle, after fourth cycle and after treatment completion.

Other Outcomes (1)

• Biological project

  During recruitment period, after patient randomization.

Study Arms (2)

R-CHOP

ACTIVE COMPARATOR

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

Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Vincristine

B-R-CAP

EXPERIMENTAL

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

Drug: Bortezomib; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone

Interventions

Bortezomib DRUG

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

Also known as: Velcade

B-R-CAP

Rituximab DRUG

Rituximab: intravenous, 375 mg/m2, day 1

B-R-CAP; R-CHOP

Cyclophosphamide DRUG

Cyclophosphamide: intravenous, 750 mg/m2, day 1

B-R-CAP; R-CHOP

Doxorubicin DRUG

Adriamycin:intravenous, 50 mg/m2, day 1

Also known as: Adriamycin

B-R-CAP; R-CHOP

Prednisone DRUG

Prednisone: oral, 100 mg, days 1-5

B-R-CAP; R-CHOP

Vincristine DRUG

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

R-CHOP

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea: lead
• Janssen-Cilag, S.A.: collaborator

Study Sites (21)

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Aragon, 50009, Spain

Location

Hospital Son Llàtzer

Palma, Balearic Islands, 07198, Spain

Location

Institut Català d'Oncologia, Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Institut Català d'Oncologia, Hospital Duran i Reynals

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital de Jerez

Jerez de la Frontera, Cádiz, 11407, Spain

Location

Hospital Universitario Fundación Alcorcón

Alcorcón, Madrid, 28922, Spain

Location

Complejo Hospitalario Universitario de Vigo

Vigo, Pontevedra, 36036, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, 33006, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, 08036, Spain

Location

Hospital Universitari de Girona Doctor Josep Trueta

Girona, 17007, Spain

Location

Hospital Universitario Infanta Leonor

Madrid, 28031, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Centro Integral Oncológico Clara Campal

Madrid, 28050, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Universitario de Canarias

Santa Cruz de Tenerife, 38320, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitario Doctor Peset

Valencia, 46017, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma

Interventions

Bortezomib; Rituximab; Cyclophosphamide; Doxorubicin; Prednisone; Vincristine

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Study Officials

• Eva González, MD

  Institut Catalá d'Oncología, Hospital Duran i Reynals

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2013
• First Posted: May 7, 2013
• Study Start: October 3, 2013
• Primary Completion: January 1, 2018
• Study Completion: August 1, 2018
• Last Updated: September 19, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (21)