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

NCT02137889 | Terminated Phase 1

• 2 other identifiers: CVAY736Y21012011-005485-38
• Study Type: interventional
• Target: 3
• Locations: 2 countries
• Sites: 2

Brief Summary

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

Conditions

Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Keywords

CLL

Outcome Measures

Primary Outcomes (1)

• 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).

  8 months

Secondary Outcomes (7)

• Overall response rate (ORR)

  1 year

• VAY736 plasma concentrations

  1 year

• Blood Serum concentrations of antibodies to VAY736

  1 year

• Hematology parameters of VAY736

  1 year

• Number of patients with Advers Events (AEs) as a measure of safety and tolerability.

  1 year

Study Arms (2)

Arm 1- relapsed/refractory CLL patients

EXPERIMENTAL

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

Drug: VAY736

Arm 2 - rituximab or ofatumumab refractory CLL patients

EXPERIMENTAL

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

Drug: VAY736

Interventions

VAY736 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 1- relapsed/refractory CLL patients; Arm 2 - rituximab or ofatumumab refractory CLL patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

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

Tampa, Florida, 33612, United States

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

MeSH Terms

Conditions

Recurrence; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ianalumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2014
• First Posted: May 14, 2014
• Study Start: July 1, 2012
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: February 28, 2018

Record last verified: 2018-02

Locations

US (1); ES (1)