Phase 2
N=28
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)
Chronic Lymphocytic Leukemia (CLL)
Bottom Line
View on ClinicalTrials.gov: NCT01532700 ↗Enrolled (actual)
28
Serious AEs
51.8%
Results posted
Sep 2019
Primary outcome: Primary: Overall Response Rate, as Per the IWCLL 2008 Response Criteria — 1; 13; 14 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Ofatumumab with GSK2110183 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- University Health Network, Toronto
- Primary completion
- Jun 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Overall Response Rate, as Per the IWCLL 2008 Response Criteria |
1; 13; 14 | — |
| SECONDARY Stable Disease, Response Rate, Toxicity (as Graded Per NCI CTC Version 4.03) |
50; 50; 71; 64; 61; 36 | — |
| SECONDARY Median Progression Free Survival, Overall Survival |
8.5; 88.3; 68.1 | — |
| SECONDARY Median Duration of Response |
6.4 | — |
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
Eligibility Criteria
Inclusion Criteria
- Patients must fulfill all of the following criteria to be eligible for admission to the study:
- A confirmed diagnosis of B-cell CLL by IWCLL 2008 criteria (Appendix 1)
- Patients must have evidence of disease progression as evidenced by rapid doubling of peripheral lymphocyte count, progressive lymphadenopathy or hepatosplenomegaly, worsening anemia or thrombocytopenia, or progressive constitutional symptoms [including fatigue, weight loss, night sweats, fever (without infection)]
- Must be relapsed or refractory to at least one prior fludarabine-containing regimen (no maximum number of prior regimens).
- Age > 18 years.
- ECOG performance status of 0, 1 or 2 (Appendix 3)
- Signed the Informed Consent form
- Life expectancy of ≥ 6 months
- Able to swallow and retain oral medication
- Normal HbA1C ≤ 0.07
- Fasting blood sugar 1 month) of systemic corticosteroids during study treatment (excludes topical or inhaled corticosteroid use)
- History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae
- QTc ≥ 470 msec on screening ECG
- Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to study entry, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities.
- Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient.
- Any major surgery within the prior 4 weeks.
- Known HIV positive
- Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.
- Positive serology for hepatitis C (HC) defined as a positive test for HCAb, in which case reflexively perform a HC RIBA immunoblot assay on the same sample to confirm the result
- Screening laboratory values: platelets ≤ 30 x 109/L,neutrophils ≤ 0.7 x 109/L,creatinine ≥ 2.0 times upper normal limit, total bilirubin ≥ 1.5 times upper normal limit (unless due to a known history of Gilbert's disease), ALT ≥ 2.5 times upper normal limit, alkaline phosphatase ≥ 2.5 times upper normal limit, INR and PTT ≤ 1.5 times upper normal limit
- Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening.
- Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as intrauterine device, double barrier method or total abstinence. Oral contraceptives are not adequate due to potential drug-drug interaction.
- Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.
Data sourced from ClinicalTrials.gov (NCT01532700). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.