Immunochemotherapy With Rituximab-Bendamustine-Cytarabine (R-BAC) for Patients With Mantle Cell Lymphoma

Lymphoma, Mantle-Cell Clinical Trial

Official title:

Immunochemotherapy With Rituximab-Bendamustine-Cytarabine for Patients With Mantle Cell Lymphoma Not Eligible for Intensive Regimens or Autologous Transplantation.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00992134
• Other study ID #: VI-1903
• Secondary ID: EudraCT 2009-009
• Status: Completed
• Phase: Phase 2
• First received: October 7, 2009
• Last updated: September 25, 2012
• Start date: June 2009
• Est. completion date: June 2012

Study information

• Verified date: September 2010
• Source: St. Bortolo Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: June 2012
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Mantle-Cell

Intervention

Drug:
• Rituximab, Bendamustine, Cytarabine
Rituximab IV 375 mg/m2 on day 1. Bendamustine IV 70 mg/m2 over a 30-60 minute infusion on day 1 and 2. Cytarabine IV 800 mg/m2, over a 2-hour infusion, 2 hours after Bendamustine, on Day 1, 2, and 3. Four to six cycles. Recycle every 28 days.

Locations

Country	Name	City	State
Italy	Department of Hematology, Ospedale San Bortolo	Vicenza	VI

Sponsors (1)

Lead Sponsor	Collaborator
St. Bortolo Hospital

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		June 2011	Yes
Secondary	Overall response and freedom from progression after R-BAC treatment		June 2011	Yes