An Open-Label Phase 2 Study of Ofatumumab (Arzerra) in Combination With Oral GSK2110183 in the Treatment of Relapsed and Refractory Chronic Lymphocytic Leukemia (CLL)
Summary
This is a phase 2, open-label, single institution trial of combination of intravenous (IV) ofatumumab and oral GSK2110183 in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL). Patients must have received at least one prior line of therapy containing fludarabine (single-agent or combination therapy). During the initial 6 months Treatment Phase, ofatumumab will be administered weekly for 8 doses, then once every 4 week cycle for an additional 4 doses (dose and schedule identical to the pivotal phase 2 trial) and GSK2110183 will be given daily PO (Treatment Phase). There will be an initial 10 day lead-in with GSK2110183 alone prior to initiation of ofatumumab to allow for evaluation of changes in cell surface expression due to GSK2110183 and for GSK2110183 pharmacokinetic studies (Lead-in Phase). The official Cycle 1 Day 1 will start on the date of first dose of ofatumumab. Cycle duration = 4 weeks. Patients will be assessed for safety, disease assessment, response, and survival on day 1 of each cycle during the Treatment Phase. A formal review of safety data by the Data Safety Monitoring Board (DSMB) after the first 6 patients have completed cycle 1 of the Treatment Phase will be performed before continuing accrual. All patients achieving SD, PR or CR by the end of the Treatment Phase will proceed to the Maintenance Phase. Patients with PD at any time, including by the end of Treatment Phase, will be taken off study. During the Maintenance Phase, single-agent GSK2110183 will be administered daily for a maximum of 12 months (12 cycles). Maximum duration on any study drug is 18 months (18 cycles). During the Follow-up Phase, patients will be assessed for safety, disease assessment, response, and survival every 3 months through month 36 (year 3), or until subsequent CLL therapy or death, whichever comes first. Key indications for study withdrawal are progressive disease, intolerable toxicity, or completion of therapy
Study Design
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Chronic Lymphocytic Leukemia (CLL)
Intervention
Ofatumumab with GSK2110183
Location
University Health Network-Princess Margaret Hospital
Toronto
Ontario
Canada
M5G 2M9
Status
Recruiting
Source
University Health Network, Toronto
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01532700
- Information obtained from ClinicalTrials.gov on March 13, 2012
Medical and Biotech [MESH] Definitions
Leukemia, Lymphocytic, Chronic, B-cell
A chronic leukemia characterized by abnormal B-lymphocytes and often generalized lymphadenopathy. In patients presenting predominately with blood and bone marrow involvement it is called chronic lymphocytic leukemia (CLL); in those predominately with enlarged lymph nodes it is called small lymphocytic lymphoma. These terms represent spectrums of the same disease.
Leukemia, Prolymphocytic
A chronic leukemia characterized by a large number of circulating prolymphocytes. It can arise spontaneously or as a consequence of transformation of CHRONIC LYMPHOCYTIC LEUKEMIA.
Leukemia, Prolymphocytic, T-cell
A lymphoid leukemia characterized by a profound LYMPHOCYTOSIS with or without LYMPHADENOPATHY, hepatosplenomegaly, frequently rapid progression, and short survival. It was formerly called T-cell chronic lymphocytic leukemia.
Leukemic Infiltration
A pathologic change in leukemia in which leukemic cells permeate various organs at any stage of the disease. All types of leukemia show various degrees of infiltration, depending upon the type of leukemia. The degree of infiltration may vary from site to site. The liver and spleen are common sites of infiltration, the greatest appearing in myelocytic leukemia, but infiltration is seen also in the granulocytic and lymphocytic types. The kidney is also a common site and of the gastrointestinal system, the stomach and ileum are commonly involved. In lymphocytic leukemia the skin is often infiltrated. The central nervous system too is a common site.
Thyroiditis
Inflammatory diseases of the THYROID GLAND. Thyroiditis can be classified into acute (THYROIDITIS, SUPPURATIVE), subacute (granulomatous and lymphocytic), chronic fibrous (Riedel's), chronic lymphocytic (HASHIMOTO DISEASE), transient (POSTPARTUM THYROIDITIS), and other AUTOIMMUNE THYROIDITIS subtypes.
Clinical Trials
The purpose of this research is to evaluate the safety and effectiveness of the drugs lenalidomide and ofatumumab in the treatment of chronic lymphocytic leukemia (CLL).
Ofatumumab Retreatment and Maintenance Treatment in CLL Patients
The purpose of the trial is to investigate the efficacy and safety of ofatumumab retreatment and maintenance in patients with chronic lymphocytic leukemia who have previously responded or...
Ofatumumab and Bendamustine for Previously Treated Chronic Lymphocytic Leukemia (CLL)
The purpose of this study is to evaluate the safety and effectiveness of the combination of bendamustine and ofatumumab in subjects with relapsed/refractory chronic lymphocytic leukemia an...
The goal of this clinical research study is to learn if the combination of lenalidomide and ofatumumab can help to control chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma...
This is an open-label study to evaluate safety, tolerability, efficacy and PK profile of ofatumumab monotherapy in Japanese follicular lymphoma (FL) or chronic lymphocytic leukemia (CLL) p...
PubMed Articles
CD20 is a widely validated, B cell-specific target for therapy in B cell malignancies. Rituximab is an anti-CD20 Ab that prolongs survival of chronic lymphocytic leukemia (CLL) patients when combined...
Oral high-dose glucocorticoids and Ofatumumab in fludarabine-resistant Chronic Lymphocytic Leukemia.
SF3B1 and other novel cancer genes in chronic lymphocytic leukemia.
The somatic genetic basis of chronic lymphocytic leukemia, a common and clinically heterogeneous leukemia occurring in adults, remains poorly understood.
