GNR-084 treatment for refractory or relapsed B-cell precursor acute lymphoblastic leukemia

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.

This study is testing a new treatment called GNR-084 to see if it can help young adults with tough-to-treat B-cell leukemia feel better.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years to 45 Years
• Sex: All
• Sponsor: AO GENERIUM (industry)
• Drugs / interventions: blinatumomab
• Locations: 3 sites (Moscow and 2 other locations)
• Trial ID: NCT04601584 on ClinicalTrials.gov

What this trial studies

This is an open-label, dose-escalating study designed to evaluate the safety and pharmacokinetics of GNR-084, a bispecific antibody targeting CD19 and CD3, in patients with refractory or relapsed B-cell precursor acute lymphoblastic leukemia (B-ALL). The study will involve sequential cohorts of patients aged 18 to 45 who have undergone multiple lines of anti-leukemia therapy and have a significant presence of bone marrow blast cells. The primary focus is to assess the drug's safety profile and its pharmacological characteristics in this challenging patient population.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 to 45 with confirmed refractory or relapsed B-cell precursor acute lymphoblastic leukemia who have received at least two prior lines of therapy.

Not a fit: Patients who have undergone hematopoietic stem cell transplantation within the last 12 weeks or have active chronic graft versus host disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat B-ALL, potentially improving outcomes and survival rates.

How similar studies have performed: While this approach using bispecific antibodies is gaining traction, the specific application of GNR-084 in this context is novel and has not been extensively tested in prior studies.

Eligibility criteria

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.

Where this trial is running

Moscow and 2 other locations

• Federal State Budget Funded Institution National Medical Research Center of Hematology, Ministry of Health of the Russian Federation (MoH of Russia) — Moscow, Russian Federation (RECRUITING)
• Almazov National Medical Research Centre — Saint Petersburg, Russian Federation (RECRUITING)
• Pavlov First Saint Petersburg State Medical University — Saint Petersburg, Russian Federation (RECRUITING)

Study contacts

• Study coordinator: Eugene V. Zuev, MD

Conditions: B-precursor Acute Lymphoblastic Leukemia, ALL, GNR-084, Leukemia, Blood Diseases, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphoid, Neoplasms by Histologic Type