Open Label Multicenter Study of CVP Followed by Iodine-131 Anti-B1 Antibody for Subjects With Untreated Low-Grade Non Hodgkin's Lymphoma.

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Lymphoma, Non-Hodgkin

Treatments: Biological: cycolophosphamide, vacristine, and pednisone (CVP) x6 cycles followed by tositumomab and iodine I 131 tositumomab.

Study type: Interventional

Funder types: Industry

Identifiers

NCT01663714

104514

Details and patient eligibility

About

This is a phase II, open-label, multicenter study of the efficacy and safety of sequential administration of CVP x 6 followed by tositumomab and iodine I 131 tositumomab (formerly referred to as tositumomab and iodine I 131 tositumomab). All patients who complete three cycles of CVP, regardless of response, will be eligible for treatment with tositumomab and iodine I 131 tositumomab. Subjects who have rapidly progressive disease prior to completing three cycles of CVP may be removed from study.

In order to proceed to tositumomab and iodine I 131 tositumomab therapy, patients must have completed six cycles of CVP within 20 weeks as described. Patients may proceed to Iodine-131 Anti-B1 Antibody if they have progressive disease documented at the response evaluation following 6 cycles of CVP. In addition, patients must still meet the eligibility inclusion exclusion criteria based upon the week 20 assessments, as applicable. Patients must also have an average of ≤25% bone marrow involved by NHL to receive treatment with tositumomab and iodine I 131 tositumomab. The dosimetric dose of tositumomab and iodine I 131 tositumomab must be given within 28 days of the response evaluation following CVP and no later than 56 days from the first day of the sixth cycle of CVP.

Full description

This is a phase II, open-label, multicenter study of the efficacy and safety sequential administration of cycolophosphamide, vacristine, and prednisone (CVP) x6 cycles followed by tositumomab and iodine I 131 tositumomab for previously untreated subjects with low-grade Non-Hodgkin's Lymphoma (NHL). CVP will be repeated every 21 days for a total of six cycles. tositumomab and iodine I 131 tositumomab will begin within 56 days following the first day of the sixth cycle of CVP. Subjects will undergo two dosing phase for the tositumomab and iodine I 131 tositumomab therapy. In the first phase, "dosimetric dose", patients will receive an infusion of unlabeled Anti-B1 Antibody (450mg) over 60 minutes followed by a 30 minute infusion (including a 10-minutes flush) of Anti-B1 (35mg) containing 5mCi of Iodine-131. Whole body gamma camera scans will be obtained on Day 0; Day 2, 3, or 4 and Day 6 or 7 following the dosimetric dose. Using the dosimetric data from three time points, a patient-specific dose of Iodine-131 will be calculated to deliver the desired total body dose of radiotherapy. In the second phase, termed the "therapeutic dose", patients will receive 60-minute infusion of unlabeled Anti-B1 Antibody (450 mg) followed by a 30-minute infusion (including a 10-minute flush) of 35 mg Anti-B1 Antibody labeled with the subjects -specific dose of Iodine-131 calculate to deliver a 75cGy total body radiation dose. Subjects who have platelet counts of 100,000-149,999 cells/mm3 will receive 65 cGy; obese patients will be dosed base upon 137% of their lean body mass. Subjects will be treated with saturated solution potassium iodide (SSKI), Lugol's solution, or potassium iodide tablets starting at least 24 hours prior to the first infusion of the tositumomab and iodine I 131 tositumomab (i.e., the dosimetric dose) and continuing for 14 days following the least infusion of tositumomab and iodine I 131 tositumomab (i.e., the therapeutic dose).

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Subjects must have a histologically confirmed initial diagnosis of low-grade non-Hodgkin's B-cell lymphoma according to the International Working Formulation (IWF) (32) (i.e., small lymphocytic with or without plasmacytoid differentiation; follicular small cleaved cell; or follicular, mixed small cleaved and large cell).
• Subjects must have Ann Arbor Stage III, Stage IV, or bulky Stage II disease at diagnosis. Bulky Stage II is defined as a mediastinal mass greater than one-third of the maximum chest diameter, or any other mass greater than or equal to 10 cm in maximum diameter.
• Subjects must have evidence that their tumor tissue expresses the CD20 antigen. Immunoperoxidase stains of paraffin-embedded tissue showing positive reactivity with L26 antibody or immunoperoxidase stains of frozen tissue showing positive reactivity with Anti B1 Antibody (Coulter Clone®) or similar commercially available CD20 antibody or evidence of CD20 positivity by flow cytometry are acceptable evidence of CD20 positivity. Testing of tumor tissue from any time in the course of the patient's disease is acceptable.
• Subjects must have a performance status of at least 60% on the Karnofsky Performance Scale and an anticipated survival of at least 3 months.
• Subjects must have an ANC≥1500 cells/mm3 and a platelet count ≥100,000 cells/mm3 within 14 days of study enrollment. These blood counts must be sustained without support of hematopoietic cytokines or transfusion of blood products.
• Subjects must have adequate renal function (defined as serum creatinine <1.5 times the upper limit of normal) and hepatic function (defined as total bilirubin <1.5 times the upper limit of normal and AST <5 times the upper limit of normal) within 14 days of study enrollment.
• Subjects must have bi-dimensionally measurable disease. At least one lesion must be ≥2.0x2.0 cm by computerized tomography scan.
• Subjects must be at least 18 years of age.
• Subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to study enrollment.
• Subjects must give written informed consent and sign an IRB-approved informed consent form prior to study enrollment.

Exclusion criteria

• Subjects who have received prior chemotherapy, biologic therapy, steroids, or radiation therapy as treatment for their NHL.
• Subjects with active obstructive hydronephrosis.
• Subjects with New York Heart Association class III or IV heart disease or other serious illness that would preclude evaluation.
• Subjects with prior malignancy other than lymphoma, except for adequately treated skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for 5 years. Patients who have been disease-free of another cancer for greater than 5 years must be carefully assessed at the time of study entry to rule out recurrent disease.
• Subjects with known HIV infection.
• Subjects who are HAMA positive.
• Subjects with known brain or leptomeningeal metastases.
• Subjects who are pregnant or breastfeeding. Males and females must agree to use a contraceptive method from enrollment to 6 months after receiving Iodine 131 Anti B1 Antibody.
• Subjects with active infection requiring IV anti-infectives at the time of study enrollment.
• Subjects with intermediate- or high-grade NHL.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

open-label, single arm

Experimental group

Description:

cycolophosphamide, vacristine, and pednisone (CVP) x6 cycles followed by tositumomab and iodine I 131 tositumomab. CVP will be repeated every 21 days for a total of six cycles. tositumomab and iodine I 131 tositumomab will begin within 56 days following the first day of the sixth cycle of CVP. Patient will undergo two dosing phase for the tositumomab and iodine I 131 tositumomab therapy.

Treatment:

Biological: cycolophosphamide, vacristine, and pednisone (CVP) x6 cycles followed by tositumomab and iodine I 131 tositumomab.