Clinical trial NCT00831597: Bendamustine Combined With Rituximab for Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Official title: Bendamustine Combined With Rituximab for Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diffuse Large B-Cell Lymphoma
Keywords: Lymphoma
B-Cell
Lead sponsor: Pharmatech
Sponsor class: INDUSTRY
Collaborators: name: Cephalon
First posted: 2009-01-29
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A phase II trial to evaluate the efficacy and safety of combination bendamustine and rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. It is hypothesized that the BR combination will produce at least a 70% overall response rate.


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed CD20-positive, diffuse large B-cell lymphoma
* Measurable disease with at least one bidimensional lymph node or tumor mass \> 1.5 cm in the longest diameter that can be followed for response as a target lesion as measured by PET or CT
* Relapsed or refractory after at least one prior therapeutic treatment for diffuse large B-cell lymphoma. Relapsed is defined as patients who initially responded and then progressed. Refractory is defined as patients, whom in the judgment of the Investigator, received adequate prior treatment and did not respond during treatment or progressed within 60 days of last treatment. Relapse following an autologous stem cell transplant allowed.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-2
* Patient must understand and voluntarily sign IRB-approved informed consent
* Life expectancy ≥ three (3) months
* Age ≥ 18 years old
* Laboratory parameters:

  * Absolute neutrophil count ≥ 1,000 cells/mm(3)
  * Platelet count ≥ 75,000 cells/mm(3)
  * Hemoglobin ≥ 8 g/dL
  * Creatinine ≤ 2.0 mg/dL or Creatinine Clearance ≥ 50 mL/min (calculated or 24-hr urine sample)
  * AST/SGOT 2.0 x ULN (≤ 5.0 x ULN if secondary to liver metastases)
  * ALT/SGPT 2.0 x ULN (≤ 5.0 x ULN if secondary to liver metastases)
  * Total bilirubin ≤ 2.0 x ULN

Exclusion Criteria:

* Patients with active/symptomatic central nervous system (CNS) involvement based on clinical evaluation. Previously treated CNS involvement that has remained asymptomatic for ≥ 90 days allowed if no CNS involvement shown by lumbar puncture, PET, CT or MRI.
* Prior treatment with bendamustine
* Known sensitivity to bendamustine or any component of bendamustine
* Known anaphylaxis or immunoglobulin E (IgE) mediated hypersensitivity to murine proteins or sensitivity to rituximab or any component of rituximab
* Eligible for stem cell transplant (patients who refuse procedure will not be excluded)
* Prior allogeneic stem cell transplant within 6 months of Cycle 1, Day 1
* Major surgery, not related to debulking procedures, within 21 days of Cycle 1, Day 1. Patients undergoing debulking procedures and minor surgery are allowed after a recovery period, in the judgment of the Investigator.
* Chemotherapy, immunotherapy, or irradiation within 28 days of Cycle 1, Day 1 (within 6 weeks for nitrosoureas or mitomycin). Patients on high dose corticosteroids must have tapered to a stable dose equivalent to Prednisone ≤ 15 mg per day within 28 days of Cycle 1, Day 1.
* Prior radioimmunotherapy (i.e. Zevalin®) within 10 weeks of Cycle 1, Day 1
* Prior use of investigational anti-cancer agents within 28 days of Cycle 1, Day 1
* Unresolved toxicities ≥ grade 2 from previous therapy
* Pregnant or lactating females. Females of childbearing potential (FCBP) and non-vasectomized men must agree to use effective methods of birth control during and 28 days following treatment period. FCBP must have a negative pregnancy test.
* HIV-related lymphoma
* Known active HIV or HCV infection, or known seropositivity for HIV, or current or chronic HBV or HCV infection. HBV test required at screening or within 6 months of screening and must indicate negative result. Patients with seropositivity presumed to be due to prior vaccination against Hepatitis B or resolved infection are not excluded (see HBV reactivation guidelines included in rituximab prescribing information).
* Concurrent active or history of other malignancies, except nonmelanoma skin cancer or carcinoma in situ of cervix or breast. Patients with previous malignancies are eligible provided they have been disease free for ≥ 1 year.
* Serious (grade 3-4), active, intercurrent infection requiring therapy, or deep seated or systemic mycotic infections
* Myocardial infarction within 6 months prior to registration or New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or significant conduction system abnormalities, in the judgment of the Investigator
* Thyroid disease in which thyroid function cannot be maintained within normal range, in the judgment of the Investigator
* Concurrent uncontrolled serious medical or psychiatric conditions likely to interfere with participation in this clinical study, in the judgment of the Investigator

Primary outcomes:
measure: Best Overall Response Rate (ORR) of bendamustine in combination with rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma
timeFrame: 1 year for 1st assessment and then 2.5 years for final assessment
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: 1 year for 1st assessment and then 2.5 years for final assessment
measure: Time to Progression (TTP)
timeFrame: 1 year for 1st assessment and then 2.5 years for final assessment
measure: Progression-Free Survival (PFS)
timeFrame: 1 year for 1st assessment and then 2.5 years for final assessment
measure: Safety Profile of Study Treatment
timeFrame: 1 year for 1st assessment and then 2.5 years for final assessment
measure: Overall Survival (OS)
timeFrame: 1 year for 1st assessment and then 2.5 years for final assessment
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Pharmatech Oncology Study Site
state: California
city: Fountain Valley
country: United States
facility: Pharmatech Oncology Study Site
state: California
city: Oxnard
country: United States
facility: Pharmatech Oncology Study Site
state: California
city: Washington
country: United States
facility: Pharmatech Oncology Study Site
state: District of Columbia
city: Washington
country: United States
facility: Pharmatech Oncology Study Site
state: District of Columbia
city: Boynton Beach
country: United States
facility: Pharmatech Oncology Study Site
state: Florida
city: Brooksville
country: United States
facility: Pharmatech Oncology Study Site
state: Florida
city: Gainesville
country: United States
facility: Pharmatech Oncology Study Site
state: Florida
city: Titusville
country: United States
facility: Pharmatech Oncology Study Site
state: Florida
city: Joliet
country: United States
facility: Pharmatech Oncology Study Site
state: Illinois
city: Lafayette
country: United States
facility: Pharmatech Oncology Study Site
state: Indiana
city: Muncie
country: United States
facility: Pharmatech Oncology Study Site
state: Indiana
city: Dubuque
country: United States
facility: Pharmatech Oncology Study Site
state: Iowa
city: Paducah
country: United States
facility: Pharmatech Oncology Study Site
state: Kentucky
city: York
country: United States
facility: Pharmatech Oncology Study Site
state: Maine
city: Jackson
country: United States
facility: Pharmatech Oncology Study Site
state: Mississippi
city: Chesterfield
country: United States
facility: Pharmatech Oncology Study Site
state: Missouri
city: Cherry Hill
country: United States
facility: Pharmatech Oncology Study Site
state: New Jersey
city: Phillipsburg
country: United States
facility: Pharmatech Oncology Study Site
state: New Jersey
city: Bay Shore
country: United States
facility: Pharmatech Oncology Study Site
state: New York
city: Bronx
country: United States
facility: Pharmatech Oncology Study Site
state: New York
city: East Setauket
country: United States
facility: Pharmatech Oncology Study Site
state: New York
city: Akron
country: United States
facility: Pharmatech Oncology Study Site
state: Ohio
city: Columbus
country: United States
facility: Pharmatech Oncology Study Site
state: Ohio
city: Bethlehem
country: United States
facility: Pharmatech Oncology Study Site
state: Pennsylvania
city: Gettysburg
country: United States
facility: Pharmatech Oncology Study Site
state: Pennsylvania
city: Hilton Head
country: United States
facility: Pharmatech Oncology Study Site
state: South Carolina
city: Germantown
country: United States
facility: Pharmatech Oncology Study Site
state: Tennessee
city: Austin
country: United States
facility: Pharmatech Oncology Study Site
state: Texas
city: Corpus Christi
country: United States
facility: Pharmatech Oncology Study Site
state: Texas
city: Fort Worth
country: United States
facility: Pharmatech Oncology Study Site
state: Texas
city: Lubbock
country: United States
facility: Pharmatech Oncology Study Site
state: Texas
city: Richardson
country: United States
facility: Pharmatech Oncology Study Site
state: Texas
Study officials:
affiliation: University Hospital, Stony Brook North Shore Hematology/Oncology Associates
name: Jeffrey L Vacirca, MD, FACP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vacirca JL, Acs PI, Tabbara IA, Rosen PJ, Lee P, Lynam E. Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma. Ann Hematol. 2014 Mar;93(3):403-9. doi: 10.1007/s00277-013-1879-x. Epub 2013 Aug 17.