A phase Ib, multicenter, open-label study of HCD122 administered intravenously in combination with bendamustine in patients with CD40+ follicular lymphoma who are refractory to rituximab
- Conditions
- 10025320folliculair lymphoma
- Registration Number
- NL-OMON36558
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- Not specified
- Target Recruitment
- 5
-Patients must have a confirmed diagnosis of follicular lymphoma, according to the Revised European American Lymphoma/World Health Organization [REAL/WHO] classification
-Patients must have a recent (< 6 months) restaging tissue specimen available for CD40 expression confirmation or willingness to undergo a core biopsy for confirmation of CD40 expression
-Patients must have documented CD40+ follicular lymphoma
-Patients must have progressive disease
-Patients must be refractory to rituximab, defined as:
-Progression during rituximab treatment; OR
* Progression within 6 months of last rituximab dose
-Patients must have received at least 1 prior chemotherapeutic regimen
-Patients must have a life expectancy > 3 months
- Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed to aggressive lymphoma (i.e. DLBCL)
-Patients who have a history of another primary malignancy that is currently clinically significant or currently requires active intervention
-Patients who have received prior allogeneic stem cell transplantation
-Impaired cardiac function or clinically significant cardiac disease, including any one of the following:
* New York Heart Association Class III or IV cardiac disease, including pre-existing clinically significant arrhythmia, congestive heart failure, or cardiomyopathy
* Angina pectoris * 3 months before starting study treatment
* Acute myocardial infarction * 3 months before starting study treatment
* Other clinically significant heart disease (e.g. uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen)
-Patients who have a history of acute or chronic pancreatitis, surgery of the pancreas, or any risk factors that may increase the risk of pancreatitis
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- Frequency and characteristics of DLTs at each dose level<br /><br>- Type, frequency, and severity of AEs, changes in hematology and blood<br /><br>chemistry values, assessments of physical examinations, vital signs, and<br /><br>electrocardiograms</p><br>
- Secondary Outcome Measures
Name Time Method <p>secondary<br /><br>-Type, frequency, and severity of AEs, changes in hematology and blood<br /><br>chemistry values, assessments of physical examinations, vital signs, and<br /><br>electrocardiograms<br /><br>-Overall response rate (CR and PR)<br /><br>-HCD122 and bendamustine plasma concentrations and basic PK parameters<br /><br>(AUC0-tlast, Cmax, t1/2)<br /><br>-Serum concentrations of antibodies to HCD122<br /><br><br /><br>exploratory<br /><br>-Whole blood DNA Fc*RIIIa haplotype<br /><br>-Tumor biopsy CD40 IHC H scores and CD40+ cell percentages<br /><br>-Levels of CD40 receptor occupancy by HCD122<br /><br>-Blood biomarker levels (e.g.sCD40); IHC H-scores (e.g. CD40L and CD3),<br /><br>cytogenetics [e.g. t(14;18)], and gene expression profiling in tumor biopsy<br /><br>specimens<br /><br>-Blood biomarker levels (e.g. CRP, IL-6, IL-8)<br /><br>-IHC H-scores for pharmacodynamic and cellular response markers (e.g. pAKT,<br /><br>Ki67, CC3); gene expression</p><br>