Bevacizumab + CHOP-Rituximab in Untreated Mantle Cell Lymphoma

Phase 2

Completed

Brief Summary: Primary Objective

1. To evaluate the safety profile of Bevacizumab (Bevacizumab™)- Rituximab (Rituxan®)-CHOP (RA-CHOP) in patients with newly diagnosed mantle cell lymphoma (MCL).

Secondary Objectives

1. To evaluate the response rate and time to disease progression of the RA-CHOP regimen in patients with newly diagnosed MCL.

2. To prospectively characterize the angiogenic profiles of MCL patients during RA-CHOP treatment.

Detailed Description: Bevacizumab administered at 15 mg/kg on day 1 of each of 6 cycles

Rituximab administered 375 mg/m2 on day 3 of each of 6 cycles (with usual premedications)

Standard CHOP chemotherapy administered on day 3 every 21 days (full dose) for 6 cycles of treatment

Once completed six cycles of therapy (\~18 weeks), patients will be evaluated every 3 months for the first year post treatment, then every 6 months until disease progression or death for years 2 through 5 post treatment. Patients who have disease progression will be contacted every 6 months until death to assess for survival status.

Recruitment & Eligibility

Inclusion Criteria

Histologically confirmed diagnosis of mantle cell Non-Hodgkin's Lymphoma with characteristic immunophenotypic profile: CD5(+), CD19(+) or CD20(+), cyclin D1(+), CD23(-) and CD10(-)
Patient has not received any prior anti-cancer therapy for lymphoma
Laboratory parameters (unless considered by investigator to be due to lymphoma):

Absolute neutrophil count > 1000 cells/mm3 Platelet count > 50,000 cells/mm3 Hemoglobin > 7 gm/dL Creatinine < 2.0 x ULN Total bilirubin < 2.0 x ULN

Patient has at least one tumor mass > 1.5 cm in one dimension
Available tumor tissue for correlative studies (rebiopsy to be performed if needed)
Patient is > 18 years old
Patient has KPS > 50%
Patient has signed IRB-approved informed consent
Patient agrees to use birth control for duration of study

Exclusion Criteria

Known central nervous system (CNS) involvement by lymphoma
Known hepatitis infection
Known HIV positivity
Known history of renal disease with proteinuria; urine protein:creatinine ratio ³1.0 at screening
Uncontrolled hypertension: blood pressure of >150/100 mmHg at screening
Unstable angina
History of myocardial infarction within 6 months
History of stroke within 6 months
Clinically significant peripheral vascular disease
New York Heart Association (NYHA) Grade II or greater congestive heart failure
Patient has ejection fraction < 50%
Patient is taking coumadin, or has known history of thrombosis within last 6 months
Evidence of bleeding diathesis or coagulopathy
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1, anticipation of need for major surgical procedure during the course of the study
Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 1
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
Serious, non-healing wound, ulcer, or bone fracture
Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.
Patient is pregnant or nursing
Patient is receiving other investigational drugs

Arm && Interventions

Group	Intervention	Description
Study Treatment Arm	Bevacizumab	Bevacizumab-R-CHOP therapy included bevacizumab administered at 15 mg/kg on day 1, and standard dose R-CHOP on day 3, for six 21-day cycles
Study Treatment Arm	CHOP	Bevacizumab-R-CHOP therapy included bevacizumab administered at 15 mg/kg on day 1, and standard dose R-CHOP on day 3, for six 21-day cycles
Study Treatment Arm	Rituximab	Bevacizumab-R-CHOP therapy included bevacizumab administered at 15 mg/kg on day 1, and standard dose R-CHOP on day 3, for six 21-day cycles

Primary Outcome Measures

Name	Time	Method
Number of Participants With Toxicity	38 months	Number of patients with reversible myelosuppression (Primary toxicity was reversible myelosuppression) Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate	38 Months (min 33 months, max 62 months)	Overall Response Rate measured using Kaplan-Meier survival analysis Response criteria were those reported by Cheson et al. (1999)
Progression-Free Survival	3 years	The percentage of patients who have not progressed at the three year time point. The 3-year PFS rate was estimated based on the Kaplan-Meier analysis.
Overall Survival	3 years	The percentage of patients who have survived at the three year time point. The 3-year OS rate was estimated based on the Kaplan-Meier analysis.

Locations (2): Rush University Medical Center
🇺🇸
Chicago, Illinois, United States
Weill Medical College of Cornell University
🇺🇸
New York, New York, United States