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

NCT ID: NCT04601584

Last Updated: 2024-03-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

36 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-10-15

Study Completion Date

2025-06-30

Brief Summary

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

Detailed Description

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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).

Conditions

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B-precursor Acute Lymphoblastic Leukemia ALL GNR-084

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Sequential dose-escalation cohorts in B-ALL patients
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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GNR-084, dose level 1

Anti-CD19/CD3 antibody

Group Type EXPERIMENTAL

Cohort 1, GNR-084

Intervention Type BIOLOGICAL

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

GNR-084, dose level 2

Anti-CD19/CD3 antibody

Group Type EXPERIMENTAL

Cohort 2, GNR-084

Intervention Type BIOLOGICAL

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

GNR-084, dose level 3

Anti-CD19/CD3 antibody

Group Type EXPERIMENTAL

Cohort 3, GNR-084

Intervention Type BIOLOGICAL

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

GNR-084, dose level 4

Anti-CD19/CD3 antibody

Group Type EXPERIMENTAL

Cohort 4, GNR-084

Intervention Type BIOLOGICAL

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

GNR-084, dose level 5

Anti-CD19/CD3 antibody

Group Type EXPERIMENTAL

Cohort 5, GNR-084

Intervention Type BIOLOGICAL

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

GNR-084, dose level 6

Anti-CD19/CD3 antibody

Group Type EXPERIMENTAL

Cohort 6, GNR-084

Intervention Type BIOLOGICAL

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

Interventions

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Cohort 1, GNR-084

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

Intervention Type BIOLOGICAL

Cohort 2, GNR-084

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

Intervention Type BIOLOGICAL

Cohort 3, GNR-084

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

Intervention Type BIOLOGICAL

Cohort 4, GNR-084

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

Intervention Type BIOLOGICAL

Cohort 5, GNR-084

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

Intervention Type BIOLOGICAL

Cohort 6, GNR-084

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

Intervention Type BIOLOGICAL

Other Intervention Names

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Anti-CD19/CD3 antibody Anti-CD19/CD3 antibody Anti-CD19/CD3 antibody Anti-CD19/CD3 antibody Anti-CD19/CD3 antibody Anti-CD19/CD3 antibody

Eligibility Criteria

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Inclusion Criteria

1. Voluntarily signed informed consent form to participate in the study;
2. Men and women between aged 18 to 45 inclusive;
3. Patients with incurable morphologically / immunophenotypically confirmed refractory/ relapse of B-cell precursors CD19-positive acute lymphoblastic leukemia from (Ph "-" or Ph "+").
4. Two or more previous lines of anti-leucosis therapy.
5. 5-50% of bone marrow blast cells at screening;
6. Functional status on the scale of the Eastern Cooperative Oncology Group (ECOG) 0-2 points at the screening;
7. Life expectancy ≥ 60 days;

Exclusion Criteria

1. Hematopoietic stem cells transplantation within 12 weeks prior to study inclusion;
2. 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;
3. Investigator and / or sponsor has doubts that patient will complete the study due to rapid disease progression;
4. 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
5. 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)
6. Medical history of blinatumomab and other bispecific antibodies using;
7. Persistent toxicity event of 3rd and 4th severity degrees (CTCAE ver 5.0) due to previous treatment;
8. HIV-positive status and / or detection of any hepatitis B and / or hepatitis C blood markers;
9. 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;
10. Individual sensitivity to:

* GNR-084 components / excipients;
* human or humanized investigational drug antibodies;
11. 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);
12. Any other malignant neoplasm presence at the present time or within 5 years prior to inclusion in the study;
13. 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;
14. Extramedullary lesion of any localization;
15. Other clinical trials participation within 30 days before screening;
16. Mental, physical and other reasons hindering patient to adequately assess their behavior and correctly comply with the conditions of the research protocol;
17. Pregnancy and / or lactation;
18. Male and female patients refusal to use adequate methods of contraception throughout the study;
19. Drug addiction;
20. Alcohol addiction.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AO GENERIUM

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Oksana A. Markova, MD

Role: STUDY_CHAIR

AO GENERIUM

Locations

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

Moscow, , Russia

Site Status RECRUITING

Almazov National Medical Research Centre

Saint Petersburg, , Russia

Site Status RECRUITING

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, , Russia

Site Status RECRUITING

Countries

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Russia

Central Contacts

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Eugene V. Zuev, MD

Role: CONTACT

+7 9166419698

Oksana A. Markova, MD

Role: CONTACT

+7 9854418959

References

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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.

Reference Type DERIVED
PMID: 35622074 (View on PubMed)

Related Links

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Other Identifiers

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#652 eff date 12.11.2019

Identifier Type: OTHER

Identifier Source: secondary_id

BIM-HEM-I

Identifier Type: -

Identifier Source: org_study_id

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