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B-precursor Acute Lymphoblastic LeukemiaPhase 1/2NCT04601584

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

A Phase 1/2 study testing Cohort 1, GNR-084, Cohort 2, GNR-084 and Cohort 3, GNR-084 in people with B-precursor Acute Lymphoblastic Leukemia and ALL, run by AO GENERIUM at 3 sites in Russia.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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

Who is it for?
Ages 18 to 45 years
What is being tested?
Cohort 1, GNR-084, Cohort 2, GNR-084 and Cohort 3, GNR-084
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
3 sitesRussia
Study dates
15 Oct 2020to 18 Dec 2024
Phase
Phase 1/2
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 to 45 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.
  • 5-50% 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;

Who cannot join

  • Hematopoietic stem cells transplantation within 12 weeks prior to study inclusion;
  • 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;
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  • 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;
  • Individual sensitivity to:
  • GNR-084 components / excipients;
  • human or humanized investigational drug antibodies;
  • Major surgical interventions, accompanied by hospitalization and anesthesia application within 30 days before the patient is included in the study (biopsy is not a significant surgical intervention);
  • Any other malignant neoplasm presence at the present time or within 5 years prior to inclusion in the study;
  • Known suspected Central Nervous System (CNS) lesion by any genesis now or in medical history, including, but not limited to: neuroleukemia, epilepsy, ischemic or hemorrhagic stroke, severe traumatic brain injury, dementia, Parkinson's disease, organic brain damage, cerebellar disorders, psychosis;
  • Extramedullary lesion of any localization;
  • Other clinical trials participation within 30 days before screening;
  • Mental, physical and other reasons hindering patient to adequately assess their behavior and correctly comply with the conditions of the research protocol;
  • Pregnancy and / or lactation;
  • Male and female patients refusal to use adequate methods of contraception throughout the study;
  • Drug addiction;
  • Alcohol addiction.

Trial locations and contacts

3 sites in 1 country.

Russia3 sites

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

    Moscow, 125167

  • Almazov National Medical Research Centre

    Saint Petersburg, 191014

  • Pavlov First Saint Petersburg State Medical University

    Saint Petersburg, 197022

Other trials in Russia

About this study

Official title: Dose-escalation Sequention Cohort Study of Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GNR-084 in Patients With Refractory or Relapse Acute Lymphoblastic B-cell Precursor Leukemia.

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

Read the detailed description

Acute lymphoblastic leukemias (ALL) are a heterogeneous group of malignant clonal diseases of the blood system originating from precursor cells of hematopoiesis, predominantly of lymphoid differentiation.

More than 7,200 new cases of ALL are diagnosed annually in the European Union (EU), with approximately 40% (approximately 3,000 cases) occurring in adults The main reason for the failure of treatment of acute B-cell lymphoblastic leukemias (B-ALL) is the primary refractoriness to chemical exposure and relapses of the disease, which actually occur in 40-50% of adult patients with ALL. The prognosis in these cases is regarded as extremely unfavorable. Escalation of the chemotherapeutic approach is associated with the development of severe toxic infectious and hemorrhagic complications.

The active substance of the preparation GNR-084 is a bispecific antibody to CD19 / CD3 in the BiMS format (bispecific IgG-like molecules).

Being tested
Cohort 1, GNR-084, Cohort 2, GNR-084, Cohort 3, GNR-084, Cohort 4, GNR-084, Cohort 5, 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
Medical subject headings
Leukemia, Hematologic Diseases, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphoid, Neoplasms by Histologic Type, Neoplasms, Lymphoproliferative Disorders, Lymphatic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cohort 1, GNR-084Biological

    Also called Anti-CD19/CD3 antibody

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

  • Cohort 2, GNR-084Biological

    Also called Anti-CD19/CD3 antibody

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

  • Cohort 3, GNR-084Biological

    Also called Anti-CD19/CD3 antibody

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

  • Cohort 4, GNR-084Biological

    Also called Anti-CD19/CD3 antibody

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

  • Cohort 5, GNR-084Biological

    Also called Anti-CD19/CD3 antibody

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

  • Cohort 6, GNR-084Biological

    Also called Anti-CD19/CD3 antibody

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

Study groups in NCT04601584
Study groupRoleWhat they receive
GNR-084, dose level 1ExperimentalAnti-CD19/CD3 antibody
Receives: Biological: Cohort 1, GNR-084
GNR-084, dose level 2ExperimentalAnti-CD19/CD3 antibody
Receives: Biological: Cohort 2, GNR-084
GNR-084, dose level 3ExperimentalAnti-CD19/CD3 antibody
Receives: Biological: Cohort 3, GNR-084
GNR-084, dose level 4ExperimentalAnti-CD19/CD3 antibody
Receives: Biological: Cohort 4, GNR-084
GNR-084, dose level 5ExperimentalAnti-CD19/CD3 antibody
Receives: Biological: Cohort 5, GNR-084
GNR-084, dose level 6ExperimentalAnti-CD19/CD3 antibody
Receives: Biological: Cohort 6, GNR-084

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Week 10

Secondary outcomes (23)

  1. The frequency of specific toxicity events

    Measured: Week 104

  2. GNR-084 Peak Plasma Concentration (Cmax)

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

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

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

  4. GNR-84 half-life (T1/2)

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

  5. GNR-084 elimination rate constant (Kel)

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

  6. GNR-084 mean retention time (MRT)

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

  7. GNR-084 overall clearance (Cl)

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

  8. GNR-084 kinetic volume of distribution (Vz)

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

  9. Peripheral blood B-lymphocyte depletion (CD19, CD20).

    Measured: First infusion: 5 minutes before administration, 30 minutes, 1, 24, 48, 96 and 144 hours after infusion. Other infusions: 5 minutes before administration and 1 hour after infusion

  10. CD45+ peripheral cell count

    Measured: First infusion: 5 minutes before administration, 30 minutes, 1, 24, 48, 96 and 144 hours after infusion. Other infusions: 5 minutes before administration and 1 hour after infusion

  11. Peripheral T-lymphocytes count (CD3, CD4, CD8)

    Measured: First infusion: 5 minutes before administration, 30 minutes, 1, 24, 48, 96 and 144 hours after infusion. Other infusions: 5 minutes before administration and 1 hour after infusion

  12. Peripheral T-memory cells (CD45RA+, CD28+, CCR7+) count

    Measured: First infusion: 5 minutes before administration, 30 minutes, 1, 24, 48, 96 and 144 hours after infusion. Other infusions: 5 minutes before administration and 1 hour after infusion

  13. Peripheral B-cells/T-cells ratio

    Measured: First infusion: 5 minutes before administration, 30 minutes, 1, 24, 48, 96 and 144 hours after infusion. Other infusions: 5 minutes before administration and 1 hour after infusion

  14. Cytokine dynamics

    Measured: First infusion: 5 minutes before administration, 30 minutes, 1, 24, 48, 96 and 144 hours after infusion. Other infusions: 5 minutes before administration and 1 hour after infusion

  15. Immunogenicity

    Measured: Week 33

  16. Objective response rate (ORR)

    Measured: After 2 and 5 GNR-084 cycles (each cycle is 28 days)

  17. Complete clinical and hematological remission rate (CR)

    Measured: After 2 and 5 GNR-084 cycles (each cycle is 28 days)

  18. Frequency of complete remission with incomplete restoration of blood cellularity (CRi)

    Measured: After 2 and 5 GNR-084 cycles (each cycle is 28 days)

  19. Duration of an objective response (DoR)

    Measured: Week 104

  20. Relapse-free survival (RFS)

    Measured: Week 104

  21. Event-free survival (EFS)

    Measured: Week 104

  22. Overall survival (OS)

    Measured: Week 104

  23. Minimal residual disease (MRD) (-) rate in CR-patient

    Measured: After 5 GNR-084 cycles (each cycle is 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2020
  2. Study start15 Oct 2020
  3. Primary completion18 Dec 2024
  4. Study completion18 Dec 2024

Why it stopped: The sponsor discontinued the development of the drug for reasons other than safety.

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Sequential dose-escalation cohorts in B-ALL patients
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04601584
Sponsor's protocol ID
BIM-HEM-I
Other IDs
#652 eff date 12.11.2019
Status last verified
Sep 2026
First submitted
13 Oct 2020
Last updated
21 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 35622074

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cohort 1, GNR-084, Cohort 2, GNR-084 and Cohort 3, GNR-084 in people with B-precursor Acute Lymphoblastic Leukemia and ALL, run by AO GENERIUM at 3 sites in Russia.

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 7 inclusion and 29 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 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Russia. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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: The sponsor discontinued the development of the drug for reasons other than safety.). 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?

GNR-084 safety and tolerability. (time frame: Week 10). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04601584, which also lists 1 linked publication.

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 21 Sep 2026; AzTrials last refreshed its copy on 7 Nov 2026.

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