GNR-084 Safety and Pharmacological Characteristics in Refractory or Relapse B-cell Precursor ALL

NCT04601584 | Recruiting Phase 1 DMC

• 2 other identifiers: BIM-HEM-I#652 eff date 12.11.2019
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 3

Brief Summary

It is an open-label dose-escalating study in sequential cohorts to assess safety and pharmacokinetics of GNR-084.

Conditions

B-precursor Acute Lymphoblastic Leukemia; ALL; GNR-084

Keywords

Leukemia; GNR-084; ALL; Blood Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Antineoplastic Agents

Outcome Measures

Primary Outcomes (1)

• GNR-084 safety and tolerability.

  The GNR-084 safety and tolerability will be assessed based on an analysis of the frequency of adverse events (AEs) over the period of treatment and observation of patients

  Week 10

Secondary Outcomes (23)

• The frequency of specific toxicity events

  Week 104

• GNR-084 Peak Plasma Concentration (Cmax)

  First infusion: 5 minutes before administration, immediately after infusion, 30 minutes, 1, 3, 6, 12, 18, 24, 48, 72, 96 hours after infusion.

• GNR-084 area under the plasma concentration versus time curve (AUC)

  First infusion: 5 minutes before administration, immediately after infusion, 30 minutes, 1, 3, 6, 12, 18, 24, 48, 72, 96 hours after infusion.

• GNR-84 half-life (T1/2)

  First infusion: 5 minutes before administration, immediately after infusion, 30 minutes, 1, 3, 6, 12, 18, 24, 48, 72, 96 hours after infusion.

• GNR-084 elimination rate constant (Kel)

  First infusion: 5 minutes before administration, immediately after infusion, 30 minutes, 1, 3, 6, 12, 18, 24, 48, 72, 96 hours after infusion.

Study Arms (6)

GNR-084, dose level 1

EXPERIMENTAL

Anti-CD19/CD3 antibody

Biological: Cohort 1, GNR-084

GNR-084, dose level 2

EXPERIMENTAL

Anti-CD19/CD3 antibody

Biological: Cohort 2, GNR-084

GNR-084, dose level 3

EXPERIMENTAL

Anti-CD19/CD3 antibody

Biological: Cohort 3, GNR-084

GNR-084, dose level 4

EXPERIMENTAL

Anti-CD19/CD3 antibody

Biological: Cohort 4, GNR-084

GNR-084, dose level 5

EXPERIMENTAL

Anti-CD19/CD3 antibody

Biological: Cohort 5, GNR-084

GNR-084, dose level 6

EXPERIMENTAL

Anti-CD19/CD3 antibody

Biological: Cohort 6, GNR-084

Interventions

Cohort 1, GNR-084 BIOLOGICAL

0.01 ng/kg 6-hours intravenous infusion once a week; 4 doses per cycle, up to 5 cycles

Also known as: Anti-CD19/CD3 antibody

GNR-084, dose level 1

Cohort 2, GNR-084 BIOLOGICAL

0.1 ng/kg 6-hours intravenous infusion once a week; 4 doses per cycle, up to 5 cycles

Also known as: Anti-CD19/CD3 antibody

GNR-084, dose level 2

Cohort 3, GNR-084 BIOLOGICAL

1 ng/kg 6-hours intravenous infusion once a week; 4 doses per cycle, up to 5 cycles

Also known as: Anti-CD19/CD3 antibody

GNR-084, dose level 3

Cohort 4, GNR-084 BIOLOGICAL

4 ng/kg 6-hours intravenous infusion once a week; 4 doses per cycle, up to 5 cycles

Also known as: Anti-CD19/CD3 antibody

GNR-084, dose level 4

Cohort 5, GNR-084 BIOLOGICAL

10 ng/kg 6-hours intravenous infusion once a week; 4 doses per cycle, up to 5 cycles

Also known as: Anti-CD19/CD3 antibody

GNR-084, dose level 5

Cohort 6, GNR-084 BIOLOGICAL

20 ng/kg 6-hours intravenous infusion once a week; 4 doses per cycle, up to 5 cycles

Also known as: Anti-CD19/CD3 antibody

GNR-084, dose level 6

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Voluntarily signed informed consent form to participate in the study;
• Men and women between aged 18 to 45 inclusive;
• Patients with incurable morphologically / immunophenotypically confirmed refractory/ relapse of B-cell precursors CD19-positive acute lymphoblastic leukemia from (Ph "-" or Ph "+").
• Two or more previous lines of anti-leucosis therapy.
• % of bone marrow blast cells at screening;
• Functional status on the scale of the Eastern Cooperative Oncology Group (ECOG) 0-2 points at the screening;
• Life expectancy ≥ 60 days;

You may not qualify if:

• Active and widespread chronic graft versus host (GVHD) reaction (grade II-IV), including taking immunosuppressants for the prevention and treatment of GVHD within 2 weeks prior the GNR-084 infusion;
• Investigator and / or sponsor has doubts that patient will complete the study due to rapid disease progression;
• Chemotherapeutic agent using within 14 days prior the first GNR-084 infusion;
• Exceptions:
• Emergency leukapheresis;
• Emergency hydroxyurea using due to hyperleukocytosis for ≤ 7 days;
• Other supportive care, including antibiotics, at Investigator's discretion
• Biochemical blood test:
• The level of total bilirubin\> 1.5 upper limit of norm;
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT)\> 3 upper limit of norm;
• Glomerular filtration rate (GFR) level ≤30 (СKD-EPI)
• Medical history of blinatumomab and other bispecific antibodies using;
• Persistent toxicity event of 3rd and 4th severity degrees (CTCAE ver 5.0) due to previous treatment;
• HIV-positive status and / or detection of any hepatitis B and / or hepatitis C blood markers;
• Severe cardiovascular diseases: uncontrolled arterial hypertension, New York Heart Association (NYHA) functional class III or IV chronic heart failure, unstable angina pectoris, stroke, myocardial infarction, transient ischemic attack, coronary artery bypass grafting and coronary revascularization within last 12 months, or signs of pericardial effusion;

Sponsors & Collaborators

• AO GENERIUM: lead

Study Sites (3)

Federal State Budget Funded Institution National Medical Research Center of Hematology, Ministry of Health of the Russian Federation (MoH of Russia)

Moscow, 125167, Russia

RECRUITING

Almazov National Medical Research Centre

Saint Petersburg, 191014, Russia

RECRUITING

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, 197022, Russia

RECRUITING

Related Publications (1)

• Shi Z, Zhu Y, Zhang J, Chen B. Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia. Hematology. 2022 Dec;27(1):642-652. doi: 10.1080/16078454.2022.2074704.

  PMID: 35622074 DERIVED

Related Links

• Clinical trial registry, Ministry of Health of Russian Federation

MeSH Terms

Conditions

Leukemia; Hematologic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Pathological Conditions, Signs and Symptoms

Study Officials

• Oksana A. Markova, MD

  AO GENERIUM

  STUDY CHAIR

Central Study Contacts

Eugene V. Zuev, MD

CONTACT

+7 9166419698; evzuev@generium.ru

Oksana A. Markova, MD

CONTACT

+7 9854418959; oamarkova@generium.ru

Study Design

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

Model Details: Sequential dose-escalation cohorts in B-ALL patients

Study Record Dates

• First Submitted: October 13, 2020
• First Posted: October 26, 2020
• Study Start: October 15, 2020
• Primary Completion: February 1, 2025
• Study Completion: June 1, 2025
• Last Updated: March 6, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

RU (3)