Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VAY736 in Relapsed or Refractory CLL Patients

NCT ID: NCT02137889

Last Updated: 2018-02-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2012-11-30

Brief Summary

This study will assess the safety and preliminary efficacy of escalating doses of VAY736 in relapsed or refractory CLL patients.

Detailed Description

This Phase 1, multicenter, open-label, study will investigate the safety, pharmacokinetics, pharmacodynamics, and preliminary antil-CLL activity of VAY736 in patients with relapsed/refractory CLL who have received at least two prior regimens. The study will include one arm in the dose escalation phase and two arms in the dose expansion phase.

Conditions

Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1- relapsed/refractory CLL patients

Patients with relapsed/refractory CLL with two or three prior treatment regimens

Group Type: EXPERIMENTAL

VAY736

Intervention Type: DRUG

VAY736 is a human immunoglobulin of the G class (IgG1/k) monoclonal antibody (mAb) designed to specifically bind the BAFF receptor. VAY736 binds primarily to B-cells through its fragment antigen binding (Fab) region, in human whole blood and spleen samples; it does not bind to natural killer (NK) cells, monocytes, dendritic cells, granulocytes, or platelets.

Arm 2 - rituximab or ofatumumab refractory CLL patients

Patients with relapsed/refractory CLL with four or more prior treatment regimens

Group Type: EXPERIMENTAL

VAY736

Intervention Type: DRUG

VAY736 is a human immunoglobulin of the G class (IgG1/k) monoclonal antibody (mAb) designed to specifically bind the BAFF receptor. VAY736 binds primarily to B-cells through its fragment antigen binding (Fab) region, in human whole blood and spleen samples; it does not bind to natural killer (NK) cells, monocytes, dendritic cells, granulocytes, or platelets.

Interventions

VAY736

VAY736 is a human immunoglobulin of the G class (IgG1/k) monoclonal antibody (mAb) designed to specifically bind the BAFF receptor. VAY736 binds primarily to B-cells through its fragment antigen binding (Fab) region, in human whole blood and spleen samples; it does not bind to natural killer (NK) cells, monocytes, dendritic cells, granulocytes, or platelets.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Dose escalation: Relapsed/refractory CLL following at least -two prior treatment regimen
• Dose expansion:

• Arm 1: Relapsed/refractory CLL following two to three prior treatment regimens
• Arm 2: Relapsed/refractory CLL following four or more prior treatment regimens
• Discontinued any previous anti-cancer and investigational therapy including radiation, radioimmunotherapy, and monoclonal antibody therapy for at least 28 days or 5 half-lives of the investigational product, whichever is longer, before study treatment administration, and must have recovered fully from the adverse effects of such treatment before beginning study treatment
• Discontinued prior alemtuzumab therapy for at least 6 months
• Age 18 years
• Eastern cooperative oncology group (ECOG) performance status grade ≤ 1
• Life expectancy > 3 months
• Meet the following laboratory criteria (must be obtained within 14 days of enrollment):

• Adequate end-organ function as assessed by laboratory tests, as specified in the protocol.
• Written informed consent obtained prior to any screening procedures

Exclusion Criteria

• Major surgery within 28 days before study treatment or have not recovered fully from the adverse effects of any major or minor surgical procedures before study treatment
• History of another primary malignancy that is currently clinically significant or currently requires active intervention (except adequately treated in situ carcinoma of the cervix or non-melanoma carcinoma of the skin or any other curatively treated malignancy that has not been treated in the prior 3 months or expected to require treatment for recurrence during the course of the study).
• Prior anaphylactic or other severe infusion reaction such that the patient is unable to tolerate human immunoglobulin or monoclonal antibody administration
• Clinically significant central nervous system disease
• Myocardial infarction within 6 months prior to enrollment or New York Hospital Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or significant conduction system abnormalities in the opinion of the investigator
• History of an active infection requiring systemic therapy within 14 days before study treatment. Prophylactic antibiotics and antiviral therapies are permitted.
• Active autoimmune disease requiring immunosuppressive therapy
• Known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus or hepatitis B virus or any active bacterial, viral, or fungal infection requiring systemic therapy
• Ongoing corticosteroid use (>10 mg/day prednisone or equivalent)
• Pregnant or nursing (lactating) women.
• Sexually active males must use a condom during intercourse while taking the drug and for 3 months after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

H. Lee Moffitt Cancer Center & Research Institute Moffitt Cancer SC

Tampa, Florida, United States

Novartis Investigative Site

Barcelona, Catalonia, Spain

Countries

United States; Spain

Other Identifiers

2011-005485-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CVAY736Y2101

Identifier Type: -

Identifier Source: org_study_id