5%) patients received single agent chlorambucil, 22 (5%) patients received fludarabine or a fludarabine-containing regimen, 294 (71%) patients received cyclophosphamide-containing combination chemotherapy [CHOP (31%); CHOP-like (15%); CVP/COP (26%)] and 59 (14%) patients received rituximab-containing combination chemotherapy as first-line treatment.
Progression-free survival was significantly prolonged among Zeva lin-treated patients compared to those receiving no further treatment [median PFS 38 months vs. 18 months; HR 0.46 (95% CI: 0.35, 0.60) p<0.0001 Cox model stratified by response to first-line therapy and initial treatment strategy (immediate vs. watch-and-wait)]. The number of patients who died was too small to permit a reliable comparison on survival.
The results for PFS are presented in Figure 1.
Figure 1. Study 4: Kaplan-Meier Estimator for Investigator-Assessed Progression Free Survival Time
16 HOW SUPPLIED/STORAGE AND HANDLING
There are two kits necessary for preparation of the Zeva lin therapeutic regimen: one for preparation of In-111 radiolabeled Zeva lin (NDC 68152-104-04) and one for preparation of Y-90 radiolabeled Zeva lin (NDC 68152-103-03). The contents of all vials are sterile, pyrogen-free, contain no preservatives, and are not radioactive. Each kit contains four identification labels and the following four vials:
One (1) Zeva lin vial containing 3.2 mg ibritumomab tiuxetan in 2 mL 0.9% Sodium Chloride as a clear, colorless solution.
One (1) 50 mM Sodium Acetate Vial containing 13.6 mg Sodium Acetate trihydrate in 2 mL Water for Injection, USP as a clear, colorless solution.
One (1) Formulation Buffer Vial containing 750 mg Albumin (Human), 76 mg Sodium Chloride, 28 mg Sodium Phosphate Dibasic Dodecahydrate, 4 mg Pentetic Acid, 2 mg Potassium Phosphate Monobasic and 2 mg Potassium Chloride in 10 mL Water for Injection, pH 7.1 as a clear yellow to amber colored solution.
One (1) empty Reaction Vial.
Indium-111 Chloride Sterile Solution (In-111 Chloride) must be ordered separately from either GE Healthcare, or Mallinckrodt/Covidien.
Yttrium-90 Chloride Sterile Solution is shipped directly from MDS Nordion upon placement of an order for the Y-90 Zeva lin kit.
Rituximab (Rituxan®, Biogen Idec and Genentech USA) must be ordered separately.
Storage
Store kits at 2-8°C (36-46°F). Do not freeze.
17 PATIENT COUNSELING INFORMATION
Advise patients:
To contact a healthcare professional for severe signs and symptoms of infusion reactions.
To take premedications as prescribed [see Dosage and Administration (2.2) and Warnings and Precautions (5.1)].
To report any signs or symptoms of cytopenias (bleeding, easy bruising, petechiae or purpura, pallor, weakness or fatigue).
To avoid medications that interfere with platelet function, except as directed by a healthcare professional [see Warnings and Precautions (5.2)].
To seek prompt medical eva luation for diffuse rash, bullae, or desquamation of the skin or oral mucosa.
To immediately report symptoms of infection (e.g. pyrexia) [see Adverse Reactions (6.3)].
That immunization with live viral vaccines is not recommended for 12 months following the Zeva lin therapeutic regimen [see Warnings and Precautions (5.8)].
To use effective contraceptive methods during treatment and for a minimum of 12 months following Zeva lin therapy.
To discontinue nursing during and after Zeva lin treatment [see |
