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.
18 Years
70 Years
Both
Diffuse, Large B-Cell, Lymphoma
Trial Information
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.
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).
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).
- Psychiatric illnesses that could jeopardise the patient participation in the study.
- Known or suspected hypersensitivity to any of the agents of the study.
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Proportion of patients with Event-Free Survival at 2 years.
Outcome Description:
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.
Outcome 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
Safety Issue:
No
Principal Investigator
Eva González, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Institut Catalá d'Oncología, Hospital Duran i Reynals
Authority:
Spain: Spanish Agency of Medicines
Study ID:
BRCAP-GELTAMO12
NCT ID:
NCT01848132
Start Date:
May 2013
Completion Date:
March 2017
Related Keywords:
- Diffuse, Large B-Cell, Lymphoma
- Lymphoma
- Large B-Cell
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
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