Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VAY736 in Relapsed or Refractory CLL Patients (VAY736Y)

February 27, 2018 updated by: Novartis Pharmaceuticals

A Phase 1, Muticenter, Open-label, Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VAY736 When Administered Intravenously in Relapsed or Refractory Chronic Lymphocytic Leukemia Patients

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
        • Novartis Investigative Site
  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center & Research Institute Moffitt Cancer SC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Arm 1- relapsed/refractory CLL patients
Patients with relapsed/refractory CLL with two or three prior treatment regimens
Drug: 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.
Experimental: Arm 2 - rituximab or ofatumumab refractory CLL patients
Patients with relapsed/refractory CLL with four or more prior treatment regimens
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose limiting toxicities (DLTs)
Time Frame: 8 months
Frequency and characteristics of DLTs. Determination of the maximum tolerated dose (MTD) and/or the recommended dose for expansion (RDE) of VAY736 when administered weekly in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) (dose escalation only).
8 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall response rate (ORR)
Time Frame: 1 year
Determine the preliminary anti-CLL (chronic lymphocytic leukemia) activity of VAY736 at the MTD/RDE in patients with relapsed or refractory CLL.
1 year
VAY736 plasma concentrations
Time Frame: 1 year
Plasma concentrations to characterize the pharmaconinetics of VAY736
1 year
Blood Serum concentrations of antibodies to VAY736
Time Frame: 1 year
To assess the immunogenicity of VAY736.
1 year
Hematology parameters of VAY736
Time Frame: 1 year
To assess the pharmacodynamics of VAY736.
1 year
Number of patients with Advers Events (AEs) as a measure of safety and tolerability.
Time Frame: 1 year
To assess the safety and tolerability of VAY736 by type, frequency, and severity of AEs, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs, and electrocardiograms.
1 year
PharmacoKinetics (PK) parameters of VAY736
Time Frame: 1 year
PK parameters include AUC0-tlast, Cmax, T1/2
1 year
Receptor occupancy for VAY736
Time Frame: 1 year
To assess the pharmacodynamic effect of VAY736.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novartis Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 29, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 12, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 14, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 28, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 27, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CVAY736Y2101
  • 2011-005485-38 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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