Bevacizumab + CHOP-Rituximab in Untreated Mantle Cell Lymphoma

Phase II Study of Bevacizumab Plus CHOP-Rituximab in Patients With Untreated Mantle Cell Lymphoma (NHL)

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.

Study Overview

• Status: Completed
• Conditions: Untreated Mantle Cell Lymphoma
• Intervention / Treatment: Drug: Bevacizumab; Drug: Rituximab; Drug: CHOP

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • New York
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Study Treatment Arm; 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

Drug: Bevacizumab; 15 mg/kg on day 1 of each of 6 cycles; Drug: Rituximab; Rituximab will be administered prior to CHOP on day 3 of every cycle for a total of 6 cycles. The dose to be administered is: Rituximab: 375 mg/m2; Drug: CHOP; Standard CHOP chemotherapy will be administered at full dose every 21 days for a total of 6 cycles. The doses to be used are: Cyclophosphamide: 750 mg/m2 IV on day 3 Doxorubicin: 50 mg/m2 IV on day 3 Vincristine: 1.4 mg/m2 IV (not to exceed 2.0 mg total) on day 3 Prednisone: 100 mg PO days 3 - 7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Toxicity	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.	38 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Overall Response Rate measured using Kaplan-Meier survival analysis Response criteria were those reported by Cheson et al. (1999)	38 Months (min 33 months, max 62 months)
Progression-Free Survival	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.	3 years
Overall Survival	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.	3 years

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2007
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: November 20, 2006
• First Submitted That Met QC Criteria: November 20, 2006
• First Posted (Estimate): November 22, 2006

Study Record Updates

• Last Update Posted (Actual): October 20, 2017
• Last Update Submitted That Met QC Criteria: September 15, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Rituximab
• Other Study ID Numbers: 0604008463