Clinical trial NCT00553501: Epratuzumab and Rituximab in Treating Patients With Previously Untreated Follicular Non-Hodgkin Lymphoma
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: stage II grade 1 follicular lymphoma
stage II grade 2 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 IV grade 3 follicular lymphoma
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-11-04
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Overall Response
timeFrame: 12 months
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Duration of study (up to 10 years)
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Kaiser Permanente Medical Office -Vandever Medical Office
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Middletown
country: United States
facility: Middlesex Hospital Cancer Center
state: Connecticut
city: Lewes
country: United States
facility: Tunnell Cancer Center at Beebe Medical Center
state: Delaware
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Washington
country: United States
facility: Walter Reed Army Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Kokomo
country: United States
facility: Howard Community Hospital
state: Indiana
city: La Porte
country: United States
facility: Center for Cancer Therapy at LaPorte Hospital and Health Services
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: South Bend
country: United States
facility: Saint Joseph Regional Medical Center
state: Indiana
city: South Bend
country: United States
facility: South Bend Clinic
state: Indiana
city: Bettendorf
country: United States
facility: Hematology Oncology Associates of the Quad Cities
state: Iowa
city: Elkton MD
country: United States
facility: Union Hospital Cancer Program at Union Hospital
state: Maryland
city: Boston
country: United States
facility: Dana-Farber/Brigham and Women's Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
state: Massachusetts
city: Saint Joseph
country: United States
facility: Oncology Care Associates, PLLC
state: Michigan
city: St. Joseph
country: United States
facility: Lakeland Regional Cancer Care Center - St. Joseph
state: Michigan
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Concord
country: United States
facility: New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
state: New Hampshire
city: Hooksett
country: United States
facility: New Hampshire Oncology - Hematology, PA - Hooksett
state: New Hampshire
city: Laconia
country: United States
facility: Lakes Region General Hospital
state: New Hampshire
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Voorhees
country: United States
facility: Cancer Institute of New Jersey at Cooper - Voorhees
state: New Jersey
city: East Syracuse
country: United States
facility: CCOP - Hematology-Oncology Associates of Central New York
state: New York
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Kinston
country: United States
facility: Kinston Medical Specialists
state: North Carolina
city: Statesville
country: United States
facility: Iredell Memorial Hospital
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center
state: Ohio
city: Berlin
country: United States
facility: Mountainview Medical
state: Vermont
city: Burlington
country: United States
facility: Fletcher Allen Health Care - University Health Center Campus
state: Vermont
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Martinsville
country: United States
facility: Ravenel Oncology Center at Memorial Hospital of Martinsville and Henry County
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Huntington
country: United States
facility: St. Mary's Regional Cancer Center at St. Mary's Medical Center
state: West Virginia
Study officials:
affiliation: University of Vermont
name: Barbara Grant, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.