Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)Phase 1VAY736YNCT02137889
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of VAY736 in Relapsed or Refractory CLL Patients
A Phase 1 study testing VAY736 in people with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL), run by Novartis Pharmaceuticals at 2 sites in 2 countries.
Trial summary
This study will assess the safety and preliminary efficacy of escalating doses of VAY736 in relapsed or refractory CLL patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
- What is being tested?
- VAY736
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Jul 2012to Nov 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
H. Lee Moffitt Cancer Center & Research Institute Moffitt Cancer SC
Tampa, Florida, 33612
About this study
Official title: 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.
Read the 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.
- Being tested
- VAY736
- Keywords
- CLL
- Medical subject headings
- Recurrence, Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VAY736Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1- relapsed/refractory CLL patients | Experimental | Patients with relapsed/refractory CLL with two or three prior treatment regimens Receives: Drug: VAY736 |
| Arm 2 - rituximab or ofatumumab refractory CLL patients | Experimental | Patients with relapsed/refractory CLL with four or more prior treatment regimens Receives: Drug: VAY736 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities (DLTs)
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).
Measured: 8 months
Secondary outcomes (7)
Overall response rate (ORR)
Determine the preliminary anti-CLL (chronic lymphocytic leukemia) activity of VAY736 at the MTD/RDE in patients with relapsed or refractory CLL.
Measured: 1 year
VAY736 plasma concentrations
Plasma concentrations to characterize the pharmaconinetics of VAY736
Measured: 1 year
Blood Serum concentrations of antibodies to VAY736
To assess the immunogenicity of VAY736.
Measured: 1 year
Hematology parameters of VAY736
To assess the pharmacodynamics of VAY736.
Measured: 1 year
Number of patients with Advers Events (AEs) as a measure of safety and tolerability.
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.
Measured: 1 year
PharmacoKinetics (PK) parameters of VAY736
PK parameters include AUC0-tlast, Cmax, T1/2
Measured: 1 year
Receptor occupancy for VAY736
To assess the pharmacodynamic effect of VAY736.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2014 (estimated)
- Study startJul 2012
- Primary completionNov 2012
- Study completionNov 2012
Why it stopped: Study terminated on 04Oct2013 for business reasons after being on hold for 10 months. Early termination was not due to safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)Studies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02137889
- Sponsor's protocol ID
- CVAY736Y2101
- Other IDs
- 2011-005485-38
- Acronym
- VAY736Y
- Status last verified
- Feb 2018
- First submitted
- 29 Apr 2014
- Last updated
- 28 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02137889
- Acronym / sponsor ID
- VAY736Y / CVAY736Y2101
- Keywords
- CLL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated on 04Oct2013 for business reasons after being on hold for 10 months. Early termination was not due to safety concerns.
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jul 2012
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 14 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1- relapsed/refractory CLL patients | Experimental | Drug: VAY736Patients with relapsed/refractory CLL with two or three prior treatment regimens |
| Arm 2 - rituximab or ofatumumab refractory CLL patients | Experimental | Drug: VAY736Patients with relapsed/refractory CLL with four or more prior treatment regimens |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Dose escalation: Relapsed/refractory CLL following at least -two prior treatment regimen
- Dose expansion:
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VAY736VAY736 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. | Drug | Arm 1- relapsed/refractory CLL patients, Arm 2 - rituximab or ofatumumab refractory CLL patients |
Primary outcome
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).
7 secondary outcomes
Overall response rate (ORR)
Time frame: 1 year
VAY736 plasma concentrations
Time frame: 1 year
Blood Serum concentrations of antibodies to VAY736
Time frame: 1 year
Hematology parameters of VAY736
Time frame: 1 year
Number of patients with Advers Events (AEs) as a measure of safety and tolerability.
Time frame: 1 year
PharmacoKinetics (PK) parameters of VAY736
Time frame: 1 year
Receptor occupancy for VAY736
Time frame: 1 year
Results and safety
The study was stopped early (reason given: Study terminated on 04Oct2013 for business reasons after being on hold for 10 months. Early termination was not due to safety concerns.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VAY736 in people with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL), run by Novartis Pharmaceuticals at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study terminated on 04Oct2013 for business reasons after being on hold for 10 months. Early termination was not due to safety concerns.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicities (DLTs) (time frame: 8 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2018.