A study comparing the efficacy, safety, pharmacokinetics and immunogenicity of PF-05280586 versus commercially available rituximab in treating patients with low tumor burden follicular lymphoma in the first-line treatment setting.
- Conditions
- low tumor burden follicular lymphomaMedDRA version: 20.0Level: HLGTClassification code 10025320Term: Lymphomas non-Hodgkin's B-cellSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-000132-41-AT
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 394
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Male or female patients aged 18 years (or local age of maturity for providing informed consent if greater than 18 years) or older.
2. Histologically confirmed, Grade 1-3a, untreated, CD20-positive follicular lymphoma (containing no elements of diffuse large B-cell lymphoma).
NOTE: Patients can be entered based on a diagnosis of CD20+ follicular lymphoma confirmed at the investigational site. Archival tissue must be sent to the central pathology reviewer for confirmation of diagnosis. Patients must have tissue available for the central pathology review to be enrolled. 3. Ann Arbor Stage II, III, or IV.
4. Eastern Cooperative Oncology Group (ECOG) status of 0 to 1.
5. At least 1 measureable disease lesion identifiable by imaging:
• A nodal lesion must be at least 11 mm x 11 mm OR =16 mm in the greatest transverse diameter [regardless of short axis measurement].
• An extranodal lesion must be at least 10 mm x 10 mm.
6. Patient has low tumor burden FL, defined as:
a. Serum LDH =1.5 upper limit of normal.
b. ß2-microglobulin =1.5 upper limit of normal.c. Largest nodal or extra-nodal mass <7 cm in diameter.
d. No more than 3 nodal sites with a diameter >3 cm.
e. No clinically significant serous effusions detectible on chest
radiography.
f. Spleen enlargement =16 cm by CT (computed tomography) scan.g. No complications such as organ compression or impairment.
h. No B symptoms:
• fever >38?C for 3 consecutive days;
• recurrent, drenching night sweats;
• Unintentional weight loss exceeding 10% body weight in 6 months.
NOTE: Patients with mild FL symptoms may be enrolled in the study as long as they do not meet the criteria for B symptoms.
7. Men and women of childbearing potential must agree to use a highly effective method of contraception throughout the study and for 12 months after the last dose of assigned treatment. A man or woman is of childbearing potential if, in the opinion of the investigator, he or she is biologically capable of having children and is sexually active.
8. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study.
9. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 157
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 237
Patients presenting with any of the following will not be included in the study:
1. Patients who are not candidates for rituximab monotherapy in the opinion of the investigator.
2. Evidence of histologic transformation to high-grade or diffuse large Bcell
lymphoma.
3. Central nervous system or meningeal involvement or cord
compression by the lymphoma (Brain imaging is not required, but may
be conducted if clinically indicated).
4. Any previous history of T-cell lymphoma.
5. Subjects with = 5000/mm3 circulating lymphoma cells.
6. Any prior systemic therapy for B-cell NHL, including chemotherapy,
immunotherapy, or steroids. Patients may have received prior localized
radiotherapy for FL (Low dose [10 mg oral prednisone or equivalent] or
inhaled steroids for other conditions are acceptable).
7. Any prior treatment with rituximab.
8. Hypersensitivity to the active substances or to any of the excipients in rituximab-Pfizer or rituximab-EU.
9. History of allergy or prior hypersensitivity to murine, chimeric, humanized, or human monoclonal antibody treatments.
10.Impaired bone marrow function as evidenced by hemoglobin < 9.0 g/dL, absolute neutrophil count (ANC) < 1.5 x 10x9 cells/L (1500/mm3) or a platelet count <75 x 10x9cells/L (75,000/mm3).
11. Symptomatic ischemic heart disease or NYHA Class II, III, or IV congestive heart failure.
12. Active infection with tuberculosis (TB). Patients with evidence of latent TB or a history of TB must have completed treatment or have initiated treatment for at least 1 month before the first dose of study treatment (Day 1). TB testing is required only if it is required by local regulations or practice.
13. Positive test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or anti-hepatitis C antibody (HCVAb), or seropositivity for human immunodeficiency virus (HIV).
14. Any other active uncontrolled infection. Patients with an infection must have initiated a course of treatment with an effective antimicrobial a minimum of 7 days before the first dose of study treatment (Day 1) and be free of symptoms from the infection.
15. Any history of another cancer during the last 5 years with the exception of non-melanoma skin tumors, in situ cervical carcinoma, or in situ breast cancer treated with curative intent with no history of metastatic disease.
16. Administration of a live vaccine = 6 weeks before first dose of study treatment (Day 1).
17. Major surgery =28 days before first dose of study treatment.
18. Anticipated need for concomitant administration of any other experimental drug, or a concomitant chemotherapy, anticancer hormonal therapy, radiotherapy, or immunotherapy during study participation.
19. Participation in other studies involving investigational drug(s) (Phases 1-4) within 4 weeks or 5 half-lives, whichever is longer, before the current study begins and/or during study participation.
20. Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
21. Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the investigator, or patients w
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the efficacy of rituximab-Pfizer to rituximab-EU when administered as a first-line treatment to patients with CD20-positive, low tumor burden follicular lymphoma (LTB-FL).;Secondary Objective: •To evaluate the safety of rituximab-Pfizer and rituximab-EU.<br>•To evaluate the population pharmacokinetics of rituximab-Pfizer and rituximab-EU. <br>•To evaluate the immunogenicity of rituximab-Pfizer and rituximab-EU. <br>•To characterize CD19-positive B-cell depletion and recovery in patients receiving rituximab-Pfizer and rituximab-EU.<br>;Primary end point(s): Overall Response Rate (ORR) at Week 26 of rituximab-Pfizer and rituximab-EU based on central radiology review in accordance with the revised response criteria for malignant lymphoma;Timepoint(s) of evaluation of this end point: Week 26
- Secondary Outcome Measures
Name Time Method Secondary end point(s): •Safety characterized by type, incidence, severity, timing, seriousness, and relationship to study therapy of adverse events and laboratory abnormalities.<br>•Time to Treatment Failure (TTF).<br>•Progression-Free Survival (PFS). <br>•Complete Remission (CR) rate at Week 26. <br>•Duration of response.<br>•Overall survival. <br>•Peak and trough drug concentrations.<br>•CD19-positive B-cell counts.<br>•Incidence of anti-drug antibodies (ADA), including neutralizing antibodies (NAb), and safety associated with immune response. <br>;Timepoint(s) of evaluation of this end point: please refer to the 'Schedule of Activities' table provided within the protocol pages 7-9.