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.)
ConditionDiffuse, Large B-Cell, Lymphoma
InterventionDrug: Bortezomib
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Prednisone
Drug: Vincristine
PhasePhase 2
SponsorGrupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Responsible PartyGrupo Español de Linfomas y Transplante Autólogo de Médula Ósea
ClinicalTrials.gov IdentifierNCT01848132
First ReceivedMay 3, 2013
Last UpdatedApril 25, 2014
Last verifiedFebruary 2014

Tracking Information[ + expand ][ + ]

First Received DateMay 3, 2013
Last Updated DateApril 25, 2014
Start DateOctober 2013
Estimated Primary Completion DateMarch 2017
Current Primary Outcome MeasuresProportion 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
  • Event-Free survival at 2 years in the different subtypes of DLBCL [Time Frame: 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] [Designated as safety issue: No]Event-free survival at 2 years in the different subtypes of DLBCL subgroups: Germinal center B-cell-like (GCB)/non-GCB.
  • Overall survival at 2 years [Time Frame: 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.] [Designated as safety issue: No]Overall survival at 2 years in patients diagnosed of DLBCL with aIPI > 1 or aIPI=1 with elevated levels of beta 2-microglobulin (above UNL)
  • Overall response rate and complete remissions [Time Frame: 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.] [Designated as safety issue: No]Overall response rate and complete remissions in patients diagnosed of DLBCL with aIPI > 1 or aIPI=1 with elevated levels of beta 2-microglobulin (above UNL).
  • Toxicity according to the CTC criteria [Time Frame: 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.] [Designated as safety issue: Yes]Toxicity according to the Common Toxicity Criteria (CTC) (version 3.0) of the National Cancer Institute (NCI).
  • To evaluate the predictive value for EFS of interim PET/CT evaluation [Time Frame: Before treatment, after second cycle, after fourth cycle and after treatment completion.] [Designated as safety issue: No]To evaluate the predictive value for EFS of interim PET/CT evaluation after 2 and 4 cycles of chemotherapy.
    The PET Network group of Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea (GELTAMO), will conduct this blind central review in real-time (qualitative and quantitative, prospective central review of the PET scans performed)
  • To identify clinical and biological prognostic factors for response and survival. [Time Frame: Once the treatment is started, there will be weekly safety visits, a visit before each treatment cycle, a visit at day 60 after the sixth cycle and then follow-up visits every three months the first 2 years and every 6 months until the 5th year.] [Designated as safety issue: No]To identify clinical and biological prognostic factors for response and survival.

Descriptive Information[ + expand ][ + ]

Brief TitleEfficacy/Safety Study of R-CHOP vs Bortezomib-R-CAP for Young Patients With Diffuse Large B-cell Lymphoma With Poor IPI.
Official TitleMulticenter 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 TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionDiffuse, Large B-Cell, Lymphoma
InterventionDrug: 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)
  • Active Comparator: 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
  • Experimental: 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

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment127
Estimated Completion DateMarch 2017
Estimated Primary Completion DateMarch 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).
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Eva Gonzalez, MD
+34-93-2607750
e.gonzalez@iconcologia.net
Location CountriesSpain

Administrative Information[ + expand ][ + ]

NCT Number NCT01848132
Other Study ID NumbersBRCAP-GELTAMO12
Has Data Monitoring CommitteeNo
Information Provided ByGrupo Español de Linfomas y Transplante Autólogo de Médula Ósea
Study SponsorGrupo Español de Linfomas y Transplante Autólogo de Médula Ósea
CollaboratorsJanssen-Cilag, S.A.
Investigators Study Chair: Eva González, MD Institut Catalá d'Oncología, Hospital Duran i Reynals
Verification DateFebruary 2014

Locations[ + expand ][ + ]

Hospital Clínico Universitario Lozano Blesa
Zaragoza, Aragón, Spain, 50009
Contact: Luis Ramón Palomera, MD | lpalomera@salud.aragon.es
Principal Investigator: Luis Ramón Palomera, MD
Recruiting
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.net
Principal 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.es
Principal Investigator: Carlos Panizo, MD
Not yet recruiting
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 08035
Contact: Andrés López, MD | andlopez@vhebron.net
Principal Investigator: Andrés López, MD
Not yet recruiting
Hospital Clinic i Provincial de Barcelona
Barcelona, Spain, 08036
Contact: Armando López, MD | alopezg@clinic.ub.es
Principal Investigator: Armando López, MD
Recruiting
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Contact: Carlos Grande, MD | cgrande.hdoc@salud.madrid.org
Principal Investigator: Carlos Grande, MD
Recruiting
Hospital Universitario La Paz
Madrid, Spain, 28046
Contact: Miguel Ángel Canales, MD | Mcanales.hulp@salud.madrid.org
Principal 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.com
Principal 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.es
Principal Investigator: Alejandro Martín, MD
Recruiting
Hospital Universitario Virgen del Rocío
Sevilla, Spain, 41013
Contact: Estrella Carrillo, MD | estrellacarrillocruz@gmail.com
Principal 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.es
Principal Investigator: Secundino Ferrer, MD
Not yet recruiting