Clinical trial NCT00992134: Immunochemotherapy With Rituximab-Bendamustine-Cytarabine (R-BAC) for Patients With Mantle Cell Lymphoma
Official title: Immunochemotherapy With Rituximab-Bendamustine-Cytarabine for Patients With Mantle Cell Lymphoma Not Eligible for Intensive Regimens or Autologous Transplantation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, Mantle-Cell
Keywords: Lymphoma, Mantle-Cell
Bendamustine
Cytarabine
Rituximab
Treatment
Combination chemotherapy
Lead sponsor: St. Bortolo Hospital
Sponsor class: OTHER
First posted: 2009-10-09
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of the study is to demonstrate the safety, tolerability, and activity of Rituximab-Bendamustine-Cytarabine(R-BAC) regimen in patients with mantle cell lymphoma (MCL) aged 65 years or more, as well as in younger patients who are not eligible for intensive regimens including/not including autologous transplantation.

Detailed description: Since Bendamustine has recently shown promising safety and efficacy in combination with monoclonal antibodies in the treatment of patients with MCL, the goal of this study is to investigate the possible therapeutic benefit of combining Ara-C with Bendamustine and Rituximab (R-BAC). All three agents exhibit individual and unique mechanisms of action in MCL, and a synergistic or additive effect might be expected when these agents are used in combination, as suggested by the pre-clinical studies.

Eligibility criteria: Inclusion Criteria:

* Previously untreated patients with MCL aged 65 years or more, or \<65 years if not eligible for intensive treatments including/not including autologous transplantation.
* MCL patients of any age who relapse/progress or are resistant after one line of chemotherapy.
* CD20+ .
* Karnofsky score of at least 70%
* Adequate renal function (Creatinine clearance \>40 mL/min), with preserved diuresis.
* Adequate liver function: alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \<2.5 x upper limit of normal (ULN) value, total bilirubin \<2 mg/dL, unless directly attributable to the patient's tumor.
* Negative serum pregnancy test 1 week prior to treatment both for pre-menopausal women and for women who are \<2 years after onset of menopause.
* Hepatitis B core antibody (HBcAb) positive patients may be enrolled if correct antiviral prophylaxis is administered at least 2 weeks before initiating protocol treatment.
* Written informed consent.

Exclusion Criteria:

* Prior treatment with Bendamustine.
* Refractoriness to Rituximab, defined as progressive disease during a previous cycle including this drug, or relapse within 6 months to any previous cycle including Rituximab.
* Previous Rituximab infusion-related severe reactions.
* Human immunodeficiency virus (HIV) positive.
* Medical conditions or organ injuries that could interfere with administration of therapy.
* Active bacterial, viral, or fungal infection requiring systemic therapy.
* Seizure disorders requiring anticonvulsant therapy.
* Severe chronic obstructive pulmonary disease with hypoxaemia.
* History of severe cardiac disease: New York Heart Association (NYHA) functional class III-IV, myocardial infarction within 6 months, ventricular tachyarrhythmias, dilatative cardiomyopathy, or unstable angina.
* Uncontrolled diabetes mellitus.
* Active secondary malignancy.
* Known hypersensitivity or anaphylactic reactions to murine antibodies and proteins (for patients treated with Rituximab), to Bendamustine or mannitol.
* Fertile men and women of childbearing potential unless surgically sterile or using adequate measures of contraception.
* Major surgery within 4 weeks of study Day 1.
* HBsAg+ and HCV+ patients
* Any co-existing medical or psychological condition that would preclude participation in the study or compromise the patient's ability to give informed consent, or that may affect the interpretation of the results, or render the patient at high risk from treatment complications.

Primary outcomes:
measure: The safety and tolerability of R-BAC treatment will be tested to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of Ara-C when combined with Bendamustine and Rituximab.
timeFrame: June 2011
Secondary outcomes:
measure: Overall response and freedom from progression after R-BAC treatment
timeFrame: June 2011
Other outcomes:
Locations:
city: Vicenza
country: Italy
facility: Department of Hematology, Ospedale San Bortolo
state: VI
Study officials:
affiliation: Department of Hematology, San Bortolo Hospital, Vicenza
name: Carlo Visco, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Visco C, Finotto S, Zambello R, Paolini R, Menin A, Zanotti R, Zaja F, Semenzato G, Pizzolo G, D'Amore ES, Rodeghiero F. Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin lymphoma ineligible for intensive regimens or autologous transplantation. J Clin Oncol. 2013 Apr 10;31(11):1442-9. doi: 10.1200/JCO.2012.45.9842. Epub 2013 Feb 11.