Bendamustine Combined With Rituximab for Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Diffuse Large B-Cell Lymphoma Clinical Trial

— 904  

Official title:

Bendamustine Combined With Rituximab for Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00831597
• Other study ID #: PI-08904
• Secondary ID: IND Exemption Nu
• Status: Completed
• Phase: Phase 2
• First received: January 26, 2009
• Last updated: April 18, 2016
• Start date: November 2008
• Est. completion date: September 2013

Study information

• Verified date: May 2012
• Source: Pharmatech
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: September 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• bendamustine
120 mg/m2 IV, Days 1, 2 of Cycles 1-6
• rituximab
375 mg/m2 IV, Day 1 of Cycles 1-6

Locations

Country	Name	City	State
United States	Pharmatech Oncology Study Site	Akron	Ohio
United States	Pharmatech Oncology Study Site	Austin	Texas
United States	Pharmatech Oncology Study Site	Bay Shore	New York
United States	Pharmatech Oncology Study Site	Bethlehem	Pennsylvania
United States	Pharmatech Oncology Study Site	Beverly Hills	California
United States	Pharmatech Oncology Study Site	Boynton Beach	Florida
United States	Pharmatech Oncology Study Site	Bronx	New York
United States	Pharmatech Oncology Study Site	Brooksville	Florida
United States	Pharmatech Oncology Study Site	Cherry Hill	New Jersey
United States	Pharmatech Oncology Study Site	Chesterfield	Missouri
United States	Pharmatech Oncology Study Site	Columbus	Ohio
United States	Pharmatech Oncology Study Site	Corpus Christi	Texas
United States	Pharmatech Oncology Study Site	Dubuque	Iowa
United States	Pharmatech Oncology Study Site	East Setauket	New York
United States	Pharmatech Oncology Study Site	Fort Worth	Texas
United States	Pharmatech Oncology Study Site	Fountain Valley	California
United States	Pharmatech Oncology Study Site	Gainesville	Florida
United States	Pharmatech Oncology Study Site	Germantown	Tennessee
United States	Pharmatech Oncology Study Site	Gettysburg	Pennsylvania
United States	Pharmatech Oncology Study Site	Hilton Head	South Carolina
United States	Pharmatech Oncology Study Site	Jackson	Mississippi
United States	Pharmatech Oncology Study Site	Joliet	Illinois
United States	Pharmatech Oncology Study Site	Lafayette	Indiana
United States	Pharmatech Oncology Study Site	Lubbock	Texas
United States	Pharmatech Oncology Study Site	Muncie	Indiana
United States	Pharmatech Oncology Study Site	Oxnard	California
United States	Pharmatech Oncology Study Site	Paducah	Kentucky
United States	Pharmatech Oncology Study Site	Phillipsburg	New Jersey
United States	Pharmatech Oncology Study Site	Richardson	Texas
United States	Pharmatech Oncology Study Site	Titusville	Florida
United States	Pharmatech Oncology Study Site	Washington	District of Columbia
United States	Pharmatech Oncology Study Site	Washington	District of Columbia
United States	Pharmatech Oncology Study Site	York	Maine

Sponsors (2)

Lead Sponsor	Collaborator
Pharmatech	Cephalon

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Best Overall Response Rate (ORR) of bendamustine in combination with rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma		1 year for 1st assessment and then 2.5 years for final assessment	No
Secondary	Duration of Response (DOR)		1 year for 1st assessment and then 2.5 years for final assessment	No
Secondary	Time to Progression (TTP)		1 year for 1st assessment and then 2.5 years for final assessment	No
Secondary	Progression-Free Survival (PFS)		1 year for 1st assessment and then 2.5 years for final assessment	No
Secondary	Safety Profile of Study Treatment		1 year for 1st assessment and then 2.5 years for final assessment	Yes
Secondary	Overall Survival (OS)		1 year for 1st assessment and then 2.5 years for final assessment	No

External Links

•   Link
•   Link
•   Link
•   Study Publication Abstract