Efficacy/Safety Study of R-CHOP vs Bortezomib-R-CAP for Young Patients With Diffuse Large B-cell Lymphoma With Poor IPI.
Overview[ - collapse ][ - ]
Purpose | 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.) |
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Condition | Diffuse, Large B-Cell, Lymphoma |
Intervention | Drug: Bortezomib Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Prednisone Drug: Vincristine |
Phase | Phase 2 |
Sponsor | Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea |
Responsible Party | Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea |
ClinicalTrials.gov Identifier | NCT01848132 |
First Received | May 3, 2013 |
Last Updated | April 25, 2014 |
Last verified | February 2014 |
Tracking Information[ + expand ][ + ]
First Received Date | May 3, 2013 |
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Last Updated Date | April 25, 2014 |
Start Date | October 2013 |
Estimated Primary Completion Date | March 2017 |
Current Primary Outcome Measures | Proportion of patients with Event-Free Survival at 2 years. [Time Frame: 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] [Designated as safety issue: No]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. |
Current Secondary Outcome Measures |
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Descriptive Information[ + expand ][ + ]
Brief Title | Efficacy/Safety Study of R-CHOP vs Bortezomib-R-CAP for Young Patients With Diffuse Large B-cell Lymphoma With Poor IPI. |
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Official Title | Multicenter Randomized Phase II Study of Treatment With R-CHOP vs Bortezomib-R-CAP for Young Patients With Diffuse Large B-cell Lymphoma With Poor IPI. |
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). |
Study Type | Interventional |
Study Phase | Phase 2 |
Study Design | Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment |
Condition | Diffuse, Large B-Cell, Lymphoma |
Intervention | Drug: Bortezomib Bortezomib: subcutaneous, 1,3 mg/m2, day 1, 8, 15. Other Names: VelcadeDrug: Rituximab Rituximab: intravenous, 375 mg/m2, day 1 Other Names: RituximabDrug: Cyclophosphamide Cyclophosphamide: intravenous, 750 mg/m2, day 1 Other Names: CyclophosphamideDrug: Doxorubicin Adriamycin:intravenous, 50 mg/m2, day 1 Other Names: AdriamycinDrug: Prednisone Prednisone: oral, 100 mg, days 1-5 Other Names: PrednisoneDrug: Vincristine Vincristine: intravenous, 1,4 mg/m2, day 1 Other Names: Vincristine |
Study Arm (s) |
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Recruitment Information[ + expand ][ + ]
Recruitment Status | Recruiting |
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Estimated Enrollment | 127 |
Estimated Completion Date | March 2017 |
Estimated Primary Completion Date | March 2017 |
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. - Hepatitis B 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). |
Gender | Both |
Ages | 18 Years |
Accepts Healthy Volunteers | No |
Contacts | Contact: Eva Gonzalez, MD +34-93-2607750 e.gonzalez@iconcologia.net |
Location Countries | Spain |
Administrative Information[ + expand ][ + ]
NCT Number | NCT01848132 |
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Other Study ID Numbers | BRCAP-GELTAMO12 |
Has Data Monitoring Committee | No |
Information Provided By | Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea |
Study Sponsor | Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea |
Collaborators | Janssen-Cilag, S.A. |
Investigators | Study Chair: Eva González, MD Institut Catalá d'Oncología, Hospital Duran i Reynals |
Verification Date | February 2014 |
Locations[ + expand ][ + ]
Hospital Clínico Universitario Lozano Blesa | Zaragoza, Aragón, Spain, 50009 Contact: Luis Ramón Palomera, MD | lpalomera@salud.aragon.esPrincipal Investigator: Luis Ramón Palomera, MD Recruiting |
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Hospital Universitario Central de Asturias | Oviedo, Asturias, Spain, 33006 Active, not recruiting |
Institut Català d'Oncologia, Hospital Germans Trias i Pujol | Badalona, Barcelona, Spain, 08916 Active, not recruiting |
Institut Català d'Oncologia, Hospital Duran i Reynals | Hospitalet de Llobregat, Barcelona, Spain, 08908 Contact: Eva González, MD | e.gonzalez@iconcologia.netPrincipal Investigator: Eva González, MD Recruiting |
Hospital Universitario Marqués de Valdecilla | Santander, Cantabria, Spain, 39008 Active, not recruiting |
Hospital de Jerez | Jerez de la Frontera, Cádiz, Spain, 11407 Active, not recruiting |
Hospital Son Llàtzer | Palma de Mallorca, Islas Baleares, Spain, 07198 Active, not recruiting |
Hospital Universitario Fundación Alcorcón | Alcorcón, Madrid, Spain, 28922 Active, not recruiting |
Clínica Universidad de Navarra | Pamplona, Navarra, Spain, 31008 Contact: Carlos Panizo, MD | cpanizo@unav.esPrincipal Investigator: Carlos Panizo, MD Not yet recruiting |
Hospital Universitari Vall d'Hebron | Barcelona, Spain, 08035 Contact: Andrés López, MD | andlopez@vhebron.netPrincipal Investigator: Andrés López, MD Not yet recruiting |
Hospital Clinic i Provincial de Barcelona | Barcelona, Spain, 08036 Contact: Armando López, MD | alopezg@clinic.ub.esPrincipal Investigator: Armando López, MD Recruiting |
Hospital Universitario 12 de Octubre | Madrid, Spain, 28041 Contact: Carlos Grande, MD | cgrande.hdoc@salud.madrid.orgPrincipal Investigator: Carlos Grande, MD Recruiting |
Hospital Universitario La Paz | Madrid, Spain, 28046 Contact: Miguel Ángel Canales, MD | Mcanales.hulp@salud.madrid.orgPrincipal Investigator: Miguel Ángel Canales, MD Recruiting |
Hospital Universitario Infanta Leonor | Madrid, Spain, 28031 Active, not recruiting |
Centro Integral Oncológico Clara Campal | Madrid, Spain, 28050 Contact: Jaime Pérez de Oteyza, MD | jperezoteyza@hmhospitales.comPrincipal Investigator: Jaime Pérez de Oteyza, MD Recruiting |
Hospital Universitario Ramón y Cajal | Madrid, Spain, 28034 Active, not recruiting |
Hospital Universitario de Salamanca | Salamanca, Spain, 37007 Contact: Alejandro Martín, MD | amartingar@usal.esPrincipal Investigator: Alejandro Martín, MD Recruiting |
Hospital Universitario Virgen del Rocío | Sevilla, Spain, 41013 Contact: Estrella Carrillo, MD | estrellacarrillocruz@gmail.comPrincipal Investigator: Estrella Carrillo, MD Recruiting |
Hospital Universitari i Politècnic La Fe | Valencia, Spain, 46026 Active, not recruiting |
Hospital Universitario Doctor Peset | Valencia, Spain, 46017 Contact: Secundino Ferrer, MD | ferrer_sec@gva.esPrincipal Investigator: Secundino Ferrer, MD Not yet recruiting |