Open-label Study of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Auriхim

NCT03057418 | Completed Phase 1 DMC

• 1 other identifier: ONC-CON4619-01
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label study of safety, tolerability, pharmacokinetics and pharmacodynamics of Auriхim multiple doses in patients with recurrent/ refractory В-cell, CD20-positive non-Hodgkin lymphoma of low tumor grade or with follicular lymphoma, as well as in patients non-treated before for В-cell, CD20-positive non-Hodgkin lymphoma of low tumor grade. The study will be carried out in 4-6 Russian and Belarussian sites. The study will be consisted of screening period, induction (obligatory) phase and supporting (non-obligatory) phase of the investigational therapy and post-treatment follow-up period.

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Follicular

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  The number of patients with treatment-related AEs assessed by CTCAE, abnormal laboratory values and instrumental tests (ECG) that are related to treatment.

  Up to 24 weeks after the last dose

• Maximum tolerated dose (MTD) of Aurixim

  MTD is defined as maximum dose at which DLT occurs in more than 1 patient of 6

  at Day 36 after the first dose

Secondary Outcomes (4)

• Area under the plasma concentration versus time curve (AUC)

  Up to week 71

• CD19+

  Up to week 71

• Peak Plasma Concentration (Cmax)

  Up to week 71

• Elimination half-life (T1/2)

  Up to week 71

Study Arms (1)

Aurixim

EXPERIMENTAL

Dosage: 125 mg/m2, 250 mg/m2, 375 mg/m2 and 500 mg/m2. Formulation: concentrate for preparation of infusions 500 mg/50 ml and 100 mg/10 ml. Mode of administration: intravenous.

Drug: Aurixim

Interventions

Aurixim DRUG

Administration will be performed once a week during 4-week induction period, and then once per 12 weeks during supporting period, if necessary. Total maximum duration of the investigational therapy - 1 year, during which patients will receive up to 8 infusions of Aurixim.

Also known as: CON-4619

Aurixim

Eligibility Criteria

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

You may qualify if:

• To participate in the clinical study, patients must comply to the following criteria:
• Signed patient's information sheet and informed consent form
• Males and females aged ≥ 18 years
• The expected survival time not less than 6 months, with no need of an urgent intervention to eliminate life-threatening complications
• Histologically and clinically confirmed at the screening diagnosis of В-cell, CD20-positive non-Hodgkin lymphoma of low tumor grade or follicular lymphoma, according to WHO's (World Health Organization) classification as of year 2008, namely:
• Follicular lymphoma, cytological stage 1, 2 and 3a
• Lymphoma from small lymphocytes (Small Lymphocytic Lymphoma) with number of peripheral blood lymphocytes \< 5,000/mсl
• Lymphoplasmacytic lymphoma, including Waldenstrom's macroglobulinemia with paraprotein meaning (IgM ) \> 2,0 g/l
• Extranodal marginal zone B-cell lymphoma of MALT-type
• Nodal marginal zone B-cell lymphoma (± monocytoid В- lymphocytes)
• Lymphoma of lien marginal zone cells.
• Patients did not receive any therapy for the main disease, or disease recurrence, or refractivity after the previous therapy
• II, III or IV disease stage according to Ann Arbor's classification and indications for immunotherapy, in the Investigator's opinion
• The patient must have at least one 2-view measurable lesion (size by the long axis \> 1,5 cm and size by the short axis \> 1,0 cm, measured by means of CT scanner), that did not undergo radiotherapy in the past or appeared again in the course of the previous treatment.
• Patients must have an ECOG status of 0 - 2

You may not qualify if:

• The patient will be considered ineligible for the study in case he/she has any criteria listed here below:
• Chronic lymphocytic leukemia
• CNS invasion now or in the history (lymphoma of CNS or lymphomatous meningitis)
• Treatment by chemotherapeutic agents or radiotherapy within 4 weeks before screening, treatment by nitrosourea and mitomycin C within 6 weeks before screening or presence of ongoing toxicities of ≥ II grade according to CTCAE, related to the prior therapy (excluding alopecia)
• Prior treatment by MAb (monoclonal antibodies) within 3 months before screening
• Concomitant immunosupressive therapy and systemic treatment by corticosteroids on the moment of screening.
• Clinically significant cardiovascular diseases:
• Myocardial infarction within 6 months before screening
• Unstable angina within 3 months before screening
• Congestive heart failure Class III or IV according to the New York Heart Association (NYHA) criteria
• Clinically significant ventricular arrhythmia (ventricular tachycardia, ventricular fibrillation)
• QTc interval \> 460 ms (ECG) (calculated according to Fredericia formula), or a diagnosis of long QTc syndrome
• Ejection fraction of left ventricle ≤ 50% (EchoCG)
• Hypotension (systolic arterial blood pressure \< 86 mm of mercury) or bradycardia with a heart rate of \< 50 beats per min., except when caused by medications (e.g. beta-blockers)
• Uncontrolled arterial hypertension (systolic arterial blood pressure \> 170 mm of mercury or diastolic arterial blood pressure \> 105 mm of mercury)

Sponsors & Collaborators

• Biointegrator LLC: lead

Study Sites (3)

State Budgetary Public Healthcare Institution of the Nizhni Novgorod Region "Hospital of Ambulance of Dzerzhinsk city"

Dzerzhinsk, 606019, Russia

Location

Federal State Budgetary Institution "National Medical-Surgical Center n.a. N.I.Pirogov" of the Ministry of Health of the Russian Federation

Moscow, 105203, Russia

Location

Federal State Budgetary Institution "Russian Oncological Scientific Center n.a. N.N.Blokhin" of the Russian Academy of Medical Sciences

Moscow, 115478, Russia

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

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

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: February 20, 2017
• Study Start: June 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: May 23, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

RU (3)