Epratuzumab and Rituximab in Treating Patients With Previously Untreated Follicular Non-Hodgkin Lymphoma

A Phase II Trial of Extended Induction Epratuzumab (Anti-CD22 Monoclonal Antibody) (CALGB IND #XXXXX) Plus Rituximab in Previously Untreated Follicular Non-Hodgkin's Lymphoma (NHL)

RATIONALE: Monoclonal antibodies, such as epratuzumab and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving epratuzumab and rituximab together may be more effective in treating follicular non-Hodgkin lymphoma.

PURPOSE: This phase II trial is studying how well giving epratuzumab together with rituximab works in treating patients with previously untreated follicular non-Hodgkin lymphoma.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Biological: epratuzumab; Biological: rituximab

Detailed Description

OBJECTIVES:

Primary

• To determine the response rate (overall and complete) after extended induction therapy comprising epratuzumab and rituximab in patients with previously untreated CD20+ follicular non-Hodgkin lymphoma (NHL).
• To determine the time to progression after extended induction therapy comprising epratuzumab and rituximab in patients with previously untreated CD20+ follicular NHL.

Secondary

• To determine the toxicity profile of epratuzumab and rituximab in patients with previously untreated CD20+ follicular NHL.
• To establish whether the therapeutic effects of the combination of epratuzumab and rituximab are sufficiently promising to warrant evaluation in a subsequent randomized trial (in comparison to rituximab alone).
• To determine the relationship between the change in fludeoxyglucose F 18 uptake early after epratuzumab and rituximab treatment with response rate and time to progression.

OUTLINE:

• Induction therapy (month 1): Patients receive epratuzumab IV over 5-30 minutes on days 1, 8, 15, and 22 and rituximab IV on days 3, 8, 15, and 22 in the absence of disease progression or unacceptable toxicity.
• Extended induction therapy (months 3, 5, 7, and 9): Patients receive epratuzumab IV over 5-30 minutes followed by rituximab IV in weeks 12, 20, 28, and 36 in the absence of disease progression or unacceptable toxicity.

Patients receive fludeoxyglucose F 18 (FDG) subcutaneously and undergo positron emission tomography at baseline and after induction therapy to assess the degree of FDG uptake.

After completion of study treatment, patients are followed every 4 months for 2 years then every 6 months for up to 10 years.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92120
      • Kaiser Permanente Medical Office -Vandever Medical Office
    • San Francisco, California, United States, 94115
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Connecticut
    • Middletown, Connecticut, United States, 06457
      • Middlesex Hospital Cancer Center
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Tunnell Cancer Center at Beebe Medical Center
    • Newark, Delaware, United States, 19713
      • CCOP - Christiana Care Health Services
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
    • Washington, District of Columbia, United States, 20307-5001
      • Walter Reed Army Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60612-7243
      • University of Illinois Cancer Center
  • Indiana
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Fort Wayne, Indiana, United States, 46845
      • Fort Wayne Medical Oncology and Hematology
    • Kokomo, Indiana, United States, 46904
      • Howard Community Hospital
    • La Porte, Indiana, United States, 46350
      • Center for Cancer Therapy at LaPorte Hospital and Health Services
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
    • South Bend, Indiana, United States, 46617
      • Saint Joseph Regional Medical Center
    • South Bend, Indiana, United States, 46617
      • South Bend Clinic
  • Iowa
    • Bettendorf, Iowa, United States, 52722
      • Hematology Oncology Associates of the Quad Cities
  • Maryland
    • Elkton MD, Maryland, United States, 21921
      • Union Hospital Cancer Program at Union Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber/Brigham and Women's Cancer Center
  • Michigan
    • Saint Joseph, Michigan, United States, 49085
      • Oncology Care Associates, PLLC
    • St. Joseph, Michigan, United States, 49085
      • Lakeland Regional Cancer Care Center - St. Joseph
  • Missouri
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center at University of Missouri - Columbia
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  • New Hampshire
    • Concord, New Hampshire, United States, 03301
      • New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
    • Hooksett, New Hampshire, United States, 03106
      • New Hampshire Oncology - Hematology, PA - Hooksett
    • Laconia, New Hampshire, United States, 03246
      • Lakes Region General Hospital
    • Lebanon, New Hampshire, United States, 03756-0002
      • Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Cancer Institute of New Jersey at Cooper - Voorhees
  • New York
    • East Syracuse, New York, United States, 13057
      • CCOP - Hematology-Oncology Associates of Central New York
    • New York, New York, United States, 10021
      • New York Weill Cornell Cancer Center at Cornell University
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Kinston, North Carolina, United States, 28501
      • Kinston Medical Specialists
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
    • Winston-Salem, North Carolina, United States, 27157-1096
      • Wake Forest University Comprehensive Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
  • Vermont
    • Berlin, Vermont, United States, 05602
      • Mountainview Medical
    • Burlington, Vermont, United States, 05401
      • Fletcher Allen Health Care - University Health Center Campus
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
    • Martinsville, Virginia, United States, 24115
      • Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County
    • Richmond, Virginia, United States, 23298-0037
      • Virginia Commonwealth University Massey Cancer Center
  • West Virginia
    • Huntington, West Virginia, United States, 25702
      • St. Mary's Regional Cancer Center at St. Mary's Medical Center

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

DISEASE CHARACTERISTICS:

• Histologically* confirmed follicular non-Hodgkin lymphoma (NHL)

  • Previously untreated disease
  • WHO classification grade 1, 2, or 3a (> 15 centroblasts per high power field with centrocytes present) that is stage III, IV, or bulky (i.e., single mass ≥ 7 cm in any unidimensional measurement) stage II disease NOTE: *Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies; fine-needle aspirates are not acceptable for diagnosis
• Confirmed CD20 antigen expression by flow cytometry or immunohistochemistry

• Measurable disease by physical examination or imaging studies

  • Any tumor mass > 1 cm is acceptable

  • No nonmeasurable disease only, including any of the following:

    • Bone lesions
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis/pulmonis
    • Bone marrow (involvement by NHL should be noted)
• No known CNS involvement by lymphoma
• Required to participate in companion FDG-PET imaging study CALGB 580701

PATIENT CHARACTERISTICS:

• ECOG performance status ≤ 2
• Absolute neutrophil count ≥ 1,000/μL
• Platelet count ≥ 50,000/μL

• Patients with HIV infection are eligible provided they meet the following criteria:

  • No evidence of coinfection with hepatitis B or C
  • CD4+ cell count ≥ 400/mm^3
  • No evidence of resistant strains of HIV
  • If not on anti-HIV therapy, HIV viral load < 10,000 copies HIV RNA/mL
  • If on anti-HIV therapy, HIV viral load < 50 copies HIV RNA/mL
  • No history of AIDS-defining conditions
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 3 months after completion of study therapy
• No known Human Anti-Chimeric Antibody (HACA)-positivity

PRIOR CONCURRENT THERAPY:

• No prior therapy for NHL including chemotherapy, radiotherapy, or immunotherapy (e.g., monoclonal antibody-based therapy)
• More than 2 weeks since prior corticosteroids except for maintenance therapy for non-malignant disease

• No concurrent dexamethasone or other steroids as antiemetics except for the following circumstances:

  • Treatment of acute infusion reactions according to institutional procedures
• No concurrent hormonal therapy except steroids for adrenal failure OR hormones for non-disease-related conditions (e.g., insulin for diabetes)
• No other concurrent chemotherapeutic agents

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: Epratuzumab Plus Rituximab; Induction Therapy (Month 1): Epratuzumab 360 mg/m^2 by IV days 1, 8, 15 & 22; Rituximab 375 mg/m^2 by IV day 3, 8, 15 & 22 Extended Induction (Weeks 12, 20, 28 & 36) Epratuzumab 360 mg/m^2 by IV weeks 12, 20, 28 & 36; Rituximab 375 mg/m^2 by IV weeks 12, 20, 28 & 36	Biological: epratuzumab; Days 1, 8, 15, 22 and weeks 12, 20, 28, & 36: 360mg/sq m IV; Biological: rituximab; Day 3, 8, 15, 22 and weeks 12, 20, 28, & 36: 375mg/sq m IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Overall Response	Overall response is defined as achievement of a complete response (CR) or partial response (PR) as defined by the Revised Response Criteria for Malignant Lymphoma. CR: complete disappearance of all detectable disease PR: >=50% decrease in the sum of the product of diameters of indicator lesions	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival	Progression free survival (PFS) was defined as the time from registration to progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method.	Duration of study (up to 10 years)

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Barbara Grant, MD, University of Vermont

Publications and helpful links

General Publications

• Lansigan F, Barak I, Pitcher B, Jung SH, Cheson BD, Czuczman M, Martin P, Hsi E, Schoder H, Smith S, Bartlett NL, Leonard JP, Blum KA. The prognostic significance of PFS24 in follicular lymphoma following firstline immunotherapy: A combined analysis of 3 CALGB trials. Cancer Med. 2019 Jan;8(1):165-173. doi: 10.1002/cam4.1918. Epub 2018 Dec 21.
• Grant BW, Jung SH, Johnson JL, Kostakoglu L, Hsi E, Byrd JC, Jones J, Leonard JP, Martin SE, Cheson BD. A phase 2 trial of extended induction epratuzumab and rituximab for previously untreated follicular lymphoma: CALGB 50701. Cancer. 2013 Nov 1;119(21):3797-804. doi: 10.1002/cncr.28299. Epub 2013 Aug 6.

Study record dates

Study Major Dates

• Study Start: March 1, 2008
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: November 2, 2007
• First Submitted That Met QC Criteria: November 2, 2007
• First Posted (Estimate): November 4, 2007

Study Record Updates

• Last Update Posted (Estimate): July 6, 2016
• Last Update Submitted That Met QC Criteria: July 1, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: stage IV grade 3 follicular lymphoma; stage II grade 3 follicular lymphoma; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage II grade 1 follicular lymphoma; stage II grade 2 follicular lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Epratuzumab; Rituximab
• Other Study ID Numbers: CALGB-50701; U10CA031946 (U.S. NIH Grant/Contract); CDR0000572604 (Registry Identifier: NCI Physician Data Query)