Clinical trial NCT00117975: Rituximab and Galiximab in Treating Patients With Stage II, Stage III, or Stage IV Non-Hodgkin's Lymphoma
Official title: A Phase II Trial of Extended Induction Galiximab (Anti-CD80 Monoclonal Antibody) (IND #12373) Plus Rituximab in Previously Untreated Follicular Non-Hodgkin Lymphoma (NHL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous 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
contiguous stage II grade 3 follicular lymphoma
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-07-11
Enrollment: 62
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 rituximab and galiximab, 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 more than one monoclonal antibody may be a better way to block cancer growth.

PURPOSE: This phase II trial is studying how well giving rituximab together with galiximab works in treating patients with stage II, stage III, or stage IV non-Hodgkin's lymphoma.

Detailed description: OBJECTIVES:

Primary

* Determine the overall and complete response rate in patients with previously untreated CD20-positive bulky stage II or stage III or IV follicular non-Hodgkin's lymphoma treated with rituximab and galiximab.
* Determine the time to disease progression in patients treated with this regimen.

Secondary

* Determine the toxicity profile of this regimen in these patients.
* Correlate Fc receptor polymorphism profiling with response in patients treated with this regimen.

OUTLINE: This is a multicenter study.

* Induction therapy (month 1): Patients receive rituximab IV on days 1, 8, 15, and 22 and galiximab IV over 1 hour on day 3, 8, 15, and 22.
* Extended induction therapy (months 3, 5, 7, and 9): Beginning in month 3, patients receive rituximab and galiximab as above on day 1. Treatment repeats every 56 days for 4 courses in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 51 patients will be accrued for this study within 18 months.

Eligibility criteria: 1. Documentation of Disease

   1.1 Previously untreated, histologically confirmed follicular lymphoma, WHO classification, grade 1, 2, or 3a (\> 15 centroblasts per high power field with centrocytes present) which is stage III, IV, or bulky (i.e., single mass ≥ 7 cm in any unidimensional measurement) stage II.

   1.1.1 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.

   1.1.2 Failure to submit pathology specimens within 60 days of patient registration will result in the patient being declared ineligible.

   1.2 Institutional flow cytometry or immunohistochemistry must confirm CD20 antigen expression.

   1.3 Patients classified as high risk according to the Follicular Lymphoma International Prognostic Index (FLIPI) should be considered for CALGB 50102/SWOG S0016 (A Phase III Trial of CHOP vs CHOP + Rituximab vs CHOP + Iodine-131-Labeled Monoclonal Anti-B1 Antibody \[Tositumomab\] For Treatment of Newly Diagnosed Follicular Non-Hodgkin's Lymphomas).
2. Prior Treatment

   2.1 No prior therapy for non-Hodgkin lymphoma including chemotherapy, radiation or immunotherapy (e.g., monoclonal antibody-based therapy)

   2.2 No corticosteroids within two weeks prior to study, except for maintenance therapy for a non-malignant disease
3. Age - Patients must be ≥ 18 years of age
4. ECOG Performance Status - Patients must have ECOG Performance Status 0-2.
5. Measurable Disease - Measurable disease must be present either on physical examination or imaging studies.

   5.1 Non-measurable disease alone is not acceptable.

   5.2 Any tumor mass \> 1 cm is acceptable.

   5.3 Lesions that are considered non-measurable include the following:
   * Bone lesions (lesions if present should be noted)
   * Ascites
   * Pleural/pericardial effusion
   * Lymphangitis cutis/pulmonis
   * Bone marrow (involvement by non-Hodgkin lymphoma should be noted).
6. CNS Involvement - Patients must have no known CNS involvement by lymphoma.
7. HIV Infection - Patients must have no known HIV infection.

   7.1 Patients with a history of intravenous drug abuse or any behavior associated with an increased risk of HIV infection should be tested for exposure to the HIV virus.

   7.2 Patients who test positive or who are known to be infected are not eligible due to an increased risk of infection with this regimen. An HIV test is not required for entry on this protocol, but is required if the patient is perceived to be at risk.
8. Human Anti-Chimeric Antibody - Patients must have no known baseline human anti-chimeric antibody (HACA) positivity.
9. Pregnancy and Nursing Status - Patients must be non-pregnant and non-nursing.

   9.1 Due to the unknown teratogenic potential of galiximab, pregnant or nursing patients may not be enrolled.

   9.2 Women and men of reproductive potential should agree to use an effective means of birth control throughout their participation in this study.

   9.3 Appropriate methods of birth control include oral contraceptives, implantable hormonal contraceptives, or double barrier method (diaphragm plus condom).
10. Second Malignancy - Patients with a "currently active" second malignancy, other than non-melanoma skin cancers are not eligible.

    10.1 This includes Waldenstrom's Macroglobulinemia, since such patients have experienced transient increases in IgM following initiation of rituximab, with the potential for hyperviscosity syndrome requiring plasmapheresis.

    10.2 Patients are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy, and are considered by their physician to be at less than 30% risk of relapse.
11. Required Initial Laboratory Values:

    * ANC ≥ 1000/µL
    * Platelet Count ≥ 50,000/µL
    * Creatinine ≤ 2 x ULN Unless attributable to lymphoma
    * Total Bilirubin ≤ 2 x ULN\*† Unless attributable to Gilbert's disease

Primary outcomes:
measure: Overall response
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center at Georgetown University Medical Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Michael & Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute at Memorial Regional Hospital
state: Florida
city: Jupiter
country: United States
facility: Ella Milbank Foshay Cancer Center at Jupiter Medical Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Canton
country: United States
facility: Graham Hospital
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Eureka
country: United States
facility: Eureka Community Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Cottage Hospital
state: Illinois
city: Havana
country: United States
facility: Mason District Hospital
state: Illinois
city: Hopedale
country: United States
facility: Hopedale Medical Complex
state: Illinois
city: Kewanee
country: United States
facility: Kewanee Hospital
state: Illinois
city: Macomb
country: United States
facility: McDonough District Hospital
state: Illinois
city: Normal
country: United States
facility: BroMenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Community Hospital of Ottawa
state: Illinois
city: Ottawa
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Ottawa
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Community Hospital
state: Illinois
city: Princeton
country: United States
facility: Perry Memorial Hospital
state: Illinois
city: Spring Valley
country: United States
facility: St. Margaret's Hospital
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Cedar Rapids
country: United States
facility: Iowa Blood and Cancer Care
state: Iowa
city: Cedar Rapids
country: United States
facility: St. Luke's Hospital
state: Iowa
city: Cedar Rapids
country: United States
facility: Mercy Regional Cancer Center at Mercy Medical Center
state: Iowa
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
city: Bangor
country: United States
facility: CancerCare of Maine at Eastern Maine Medial Center
state: Maine
city: Worcester
country: United States
facility: UMASS Memorial Cancer Center - University Campus
state: Massachusetts
city: Minneapolis
country: United States
facility: Veterans Affairs Medical Center - Minneapolis
state: Minnesota
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri - Columbia
state: Missouri
city: Jefferson City
country: United States
facility: Capital Region Cancer Center
state: Missouri
city: St Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital
state: Missouri
city: St. Louis
country: United States
facility: Missouri Baptist Cancer Center
state: Missouri
city: Hooksett
country: United States
facility: New Hampshire Oncology-Hematology, PA - Hooksett
state: New Hampshire
city: Keene
country: United States
facility: Kingsbury Center for Cancer Care at Cheshire Medical Center
state: New Hampshire
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Manchester
country: United States
facility: Elliot Regional Cancer Center
state: New Hampshire
city: Rochester
country: United States
facility: Frisbie Memorial Hospital
state: New Hampshire
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Glens Falls
country: United States
facility: Charles R. Wood Cancer Center at Glens Falls Hospital
state: New York
city: New Hyde Park
country: United States
facility: Long Island Jewish Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: Syracuse
country: United States
facility: CCOP - Hematology-Oncology Associates of Central New York
state: New York
city: Syracuse
country: United States
facility: Community General Hospital of Greater Syracuse
state: New York
city: Gastonia
country: United States
facility: CaroMont Cancer Center at Gaston Memorial Hospital
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Radiation Oncology
state: North Carolina
city: Hendersonville
country: United States
facility: Pardee Memorial Hospital
state: North Carolina
city: Kinston
country: United States
facility: Lenoir Memorial Cancer Center
state: North Carolina
city: Wilson
country: United States
facility: Wilson Medical Center
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
state: Ohio
city: Pittsburgh
country: United States
facility: Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
state: Pennsylvania
city: Florence
country: United States
facility: McLeod Regional Medical Center
state: South Carolina
city: Greenville
country: United States
facility: Bon Secours St. Francis Health System
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
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: Huntington
country: United States
facility: St. Mary's Regional Cancer Center at St. Mary's Medical Center
state: West Virginia
Study officials:
affiliation: Roswell Park Cancer Institute
name: Myron S. Czuczman, MD
role: STUDY_CHAIR
References:
citation: Czuczman MS, Leonard JP, Johnson JL, et al.: FLIPI score is applicable and predictive of response to upfront immunotherapy in CALGB 50402: phase II trial of extended induction galiximab ([G] anti-CD80 monoclonal antibody) plus rituximab [R]. [Abstract] Blood 112 (11): A-1003, 2008.
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.