Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00486759
Other study ID # BO20603
Secondary ID
Status Terminated
Phase Phase 3
First received June 14, 2007
Last updated November 28, 2012
Start date July 2007
Est. completion date November 2011

Study information

Verified date November 2012
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

This 2-arm study was designed to compare the efficacy and safety of bevacizumab (Avastin) in combination with rituximab (MabThera) and CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin [vincristine], prednisone) chemotherapy (R-CHOP) versus rituximab plus CHOP chemotherapy (R-CHOP) in previously untreated patients with CD20-positive diffuse large B-cell lymphoma (DLBCL). Patients were randomized to receive 8 cycles of treatment with R-CHOP plus bevacizumab or R-CHOP plus placebo. Treatment with bevacizumab/placebo and R-CHOP was given either on a 2-week or 3-week schedule and bevacizumab was given at a weekly average dose of 5 mg/kg (10 mg/kg for 2-week cycles and 15 mg/kg for 3-week cycles).


Description:

An independent Data and Safety Monitoring Board (DSMB) was established to review safety data collected during the study on an ongoing basis. At its meeting in December 2009, the DSMB noted a trend for increased cardiac toxicity in the experimental arm (R-CHOP + bevacizumab) compared with the control arm (R-CHOP + placebo). Additional efficacy analyses of data from 720 randomized patients were presented at a DSMB meeting on May 22, 2010; they indicated no improvement in efficacy with the addition of bevacizumab to R-CHOP. It was noted, however, that there was an apparent increase in the risk of cardiotoxicity, premature treatment withdrawal, serious adverse events (SAEs), fatal adverse events (AEs), and perforation/ulcer in the experimental arm. Based on its assessment of an increased risk with unlikely benefit for patients randomized to the experimental arm, the DSMB recommended that further enrollment in the study be permanently halted and that bevacizumab be discontinued for any patients randomized to the experimental arm. On May 31, 2010, the sponsor took the decision to stop enrollment into the study and the bevacizumab treatment was terminated with immediate effect as recommended by the DSMB.

The study protocol was amended. The primary objective of the study was changed from evaluation of efficacy to evaluation of safety and the study was extended to include an 18-month safety follow-up period. Because enrollment was terminated prematurely resulting in fewer enrolled patients than planned, the outcome measure data are premature due to fewer than expected events.

The time frame for the reporting of serious adverse events was modified. Serious adverse events (SAE) unrelated to study treatment were reported until 1 year post-treatment or until new anti-lymphoma treatment was initiated. SAEs judged to be related to study treatment and congestive heart failure events were reported at any time during the study.


Recruitment information / eligibility

Status Terminated
Enrollment 787
Est. completion date November 2011
Est. primary completion date November 2011
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 79 Years
Eligibility Inclusion Criteria:

- Adult patients, = 18 and < 80 years of age.

- CD20-positive diffuse large B-cell lymphoma.

- Low-intermediate, high-intermediate, or high risk disease and/or bulky tumor (largest diameter = 7.5 cm).

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

Exclusion Criteria:

- Prior treatment for diffuse large B-cell lymphoma.

- Types of non-Hodgkin's lymphoma other than diffuse large B-cell lymphoma (DLBCL).

- Central nervous system (CNS) involvement of lymphoma.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment


Intervention

Drug:
Bevacizumab
Bevacizumab was administered at a dose of 15 mg/kg IV on Day 1 of each 21-day cycle for 8 cycles or at a dose 10 mg/kg IV on Day 1 of each 14-day cycle for 8 cycles. The cycle duration (14- or 21-day) was chosen by each center prior to initiation of the study and was the same for all patients enrolled at that center.
Rituximab
Rituximab was administered at a dose of 375 mg/m^2 IV on Day 1 of each 14- or 21-day cycle for 8 cycles. The cycle duration (14- or 21-day) was chosen by each center prior to initiation of the study and was the same for all patients enrolled at that center.
CHOP
Cyclophosphamide was administered at a dose of 750 mg/m^2 IV on Day 1 of each cycle. Doxorubicin was administered at a dose of 50 mg/m^2 IV on Day 1 of each cycle. Vincristine was administered at a dose of 1.4 mg/m^2 IV (maximum of 2 mg) on Day 1 of each cycle. Prednisone was administered at a dose of 100 mg orally on Days 1-5 of each cycle. All 4 drugs were administered either every 21 days for 8 cycles or every 14 days for 6 cycles. The cycle duration (14- or 21-day) was chosen by each center prior to initiation of the study and was the same for all patients enrolled at that center.
Placebo
Placebo to bevacizumab was administered on Day 1 of each 14- or 21-day cycle for 8 cycles. The cycle duration (14- or 21-day) was chosen by each center prior to initiation of the study and was the same for all patients enrolled at that center.

Locations

Country Name City State
n/a

Sponsors (2)

Lead Sponsor Collaborator
Hoffmann-La Roche Genentech, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Canada,  China,  Colombia,  Czech Republic,  Ecuador,  France,  Germany,  Greece,  Hong Kong,  Hungary,  Italy,  Korea, Republic of,  Lithuania,  Malaysia,  Mexico,  New Zealand,  Panama,  Peru,  Philippines,  Poland,  Portugal,  Russian Federation,  Slovakia,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Progression-free Survival (PFS) PFS was defined as the time from the date of randomization to the date of disease progression (PD)/relapse, as determined by the investigator, or death from any cause, whichever occurred earlier. A patient with PD/relapse must meet at least 1 of the following criteria: (1) Appearance of any new lesion > 1.0 cm in the short axis during or at the end of therapy. (2) = 50 % increase from nadir in the sum of the products of diameters (SPD, maximum diameter of a tumor x largest diameter perpendicular to the maximum diameter) of any previously involved nodes, in a single involved node, or the size of other lesions (eg, splenic or hepatic nodules). To be considered progressive disease, a lymph node with a diameter of the short axis < 1.0 cm must increase by = 50% to a size of 1.5 x 1.5 cm or > 1.5 cm in the long axis. (3) = 50 % increase in the greatest diameter of any previously identified node > 1.0 cm in its short axis or in the SPD of more than 1 node. Baseline to end of the study (up to 4 years, 4 months) No
Secondary Overall Survival Overall survival was defined as the time from the date of randomization to the date of death due to any cause. Baseline to end of the study (up to 4 years, 4 months) No
Secondary Overall Response (OR) Assessed According to the Revised Response Criteria for Malignant Lymphoma OR = a complete response (CR), an unconfirmed CR, or a partial response (PR). CR = Complete disappearance of disease and disease-related symptoms. All lymph nodes and nodal masses regressed on computed tomography (CT) to normal size (= 1.5 cm in their greatest transverse diameter for nodes > 1.5 cm prior to therapy and = 1.0 cm in their short axis for nodes 1.1-1.5 cm in their long axis and > 1.0 cm in their short axis prior to therapy). Spleen and/or liver not palpable on physical examination, normal size by imaging, and disappearance of nodules related to lymphoma. If bone marrow was involved prior to therapy, infiltrate must have cleared on repeat biopsy. PR = = 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. No increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules regressed by = 50% in their SPD or, for single nodules, in the greatest transverse diameter. No new sites of disease. At the end of treatment (Cycle 8, up to 12 months) No
See also
  Status Clinical Trial Phase
Recruiting NCT05365659 - IKS03 in Patients With Advanced B Cell Non-Hodgkin Lymphomas Phase 1
Withdrawn NCT05929716 - An Open-Label, Single Center Phase 2 Study of Magrolimab, Rituximab and Radiation as Bridging Strategy Before CAR T-Cell Therapy in Patients With Relapsed or Refractory Large B-cell Lymphoma Phase 2
Active, not recruiting NCT05024045 - Study of Oral LOXO-338 in Patients With Advanced Blood Cancers Phase 1
Recruiting NCT05016947 - Venetoclax Plus Inotuzumab for B-ALL Phase 1
Completed NCT02900716 - Safety Study of BTK Inhibitor, DTRMWXHS-12, Used Singly or in Combination, in CLL and B-cell Lymphomas Phase 1
Completed NCT03068416 - CD19-targeting, 3rd Generation CAR T Cells for Refractory B Cells Malignancy Phase 2
Not yet recruiting NCT05014100 - Orelabrutinib in Combination With R2 Regimen for R/R CD20+ B-cell Lymphoma Phase 2
Recruiting NCT05934838 - A Feasibility Trial of Tazemetostat Plus CAR T Cell Therapy in B-cell Lymphomas Phase 1
Terminated NCT04023071 - FT516 in Subjects With Advanced Hematologic Malignancies Phase 1
Active, not recruiting NCT04148430 - A Study of Anakinra to Prevent or Treat Severe Side Effects for Patients Receiving CAR-T Cell Therapy Phase 2
Completed NCT02933320 - BI-1206 and an Anti-CD20 Antibody in Patients With CD32b Positive B-cell Lymphoma or Leukaemia Phase 1/Phase 2
Active, not recruiting NCT03133221 - 1630GCC: Zydelig Maintenance in B-Cell Non-Hodgkin's Lymphoma After Autologous Stem Cell Transplantation Phase 2
Completed NCT02741388 - A Phase Ib Study of Oral Selinexor in Adult Patients With Relapsed/Refractory B-cell Lymphoma Receiving R-DHAOx or R-GDP Phase 1
Completed NCT02300402 - Detection and Characterization of Residual Masses in Lymphomas
Terminated NCT02266147 - Study of SD-101 in Combination With Localized Low-dose Radiation in Patients With Untreated Low-grade B-cell Lymphoma Phase 1/Phase 2
Terminated NCT00906841 - Study of 90Y-DOTA-hLL2 as a Consolidation Therapy After R-CHOP in Patients With Diffuse Large B-cell Lymphoma Phase 2
Completed NCT00338494 - Dose Escalation Study of Clofarabine in Patients With Relapsed or Refractory Low Grade or Intermediate-Grade B-Cell Lymphoma Phase 1
Recruiting NCT05487651 - Allogeneic NK T-Cells Expressing CD19 Specific CAR in B-Cell Malignancies Phase 1
Withdrawn NCT05570188 - Anti-CD19 Universal CAR-NK Cells Therapy Combined With HSCT for B Cell Hematologic Malignancies Phase 1/Phase 2
Recruiting NCT03281551 - Efficacy and Safety of PZ01 Treatment in Patients With r/r CD19+ B-cell Acute Lymphoblastic Leukemia/B Cell Lymphoma Phase 1