TerminatedPhase 1

Gentulizumab in Relapsed/Refractory Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Stopped: Adjusted the product development strategy.

China58 participantsStarted 2021-04-01

Plain-language summary

Gentulizumab Injection is an anti-CD47 monoclonal antibody. As a member of the immunoglobulin superfamily, CD47 is expressed at low levels on many cells of the body, including hematopoietic cells (red blood cells, lymphocytes, platelets, etc.) and non-hematopoietic cells (placenta, liver and brain cells). It is overexpressed on many types of tumors. There is abundant supportive evidence that the expression of CD47 on tumor cells, though binding to SIRP on professional phagocytes, acts to prevent tumor cell phagocytosis, inhibit antigen cross-presentation, and block the production of pro-inflammatory molecules, thus promoting the development of a "cold" tumor microenvironment. Blocking CD47 can not only stimulate phagocytosis to cancer cells, but also promote macrophage recruitment towards neoplasm. At the same time, blocking CD47 can stimulate macrophages to secrete cytokines. These cytokines and chemokines can further recruit other immune cells to neoplasms. These newly recruited immune cells can provide a positive feedback and enhance the therapeutic response of blocking CD47. Therefore, the CD47/SIRPα axis blocking appears to be a potential therapeutic target for neoplasm. Currently, no anti-CD47 antibody product has been granted marketing authorization for progressive hematological malignancies. Whereas Hu5F9-G4, a CD47 monoclonal antibody, is being tested in a series of ongoing clinical trials for AML, MDS, lymphomas and multiple solid tumors. The clinical research was designed based on non-clinical data and relevant experience of other CD47 monoclonal antibody. In this phase Ia study, "3 + 3" dose escalation method combined with rapid titration will be used to evaluate the dose limiting (DLT) toxicity of each dose group, evaluate the safety and tolerance of Gentulizumab in the treatment of patients with progressive hematological malignancies, and determine the maximum tolerated dose (MTD) and phase II recommended dose (RP2D); At the same time, the pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, preliminary efficacy and biomarkers of gentulizumab will be evaluated to provide sufficient basis for new drug application (NDA) guidance and further clinical use.

Who can participate

Age range18 Years – 75 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. The patient has the willingness to communicate with the Investigator, be able to understand and follow the trial requirements, volunteer to participate in the trial, understands and signs the written ICF, and is willing and able to comply with the visit schedule, administration plan, laboratory examination, and other clinical trial procedures.
✓. Gender: Male or female.
✓. Age ≥18
✓. Life expectancy ≥ 3 months.
✓. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
✓. Patients with relapsed/refractory AML or MDS for whom there exists no standard treatment options available.
✓. The white blood cell (WBC) count in the patient's peripheral blood must be ≤ 20 × 109/L within 7 days of the first dose of the study drug. The patients with WBC count \> 20 × 109/L may be treated with hydroxyurea (maximum dose 4 g/d) during the Screening period to achieve entry criteria. Hydroxyurea may be continued for the first 4 weeks of treatment (Cycle 1) to control blast counts at the discretion of the Investigator; hydroxyurea must be stopped after the first 4 weeks of treatment.
✓. Hb levels must be above 5 g/dL on the day of the first dose of the study drug, and may be maintained by transfusion. Transfusion is permitted in the duration of trial.

What they're measuring

adverse events (AEs)

Timeframe: ICF signing to 90 days after last administration or initiation of new anti-tumor treatment

serious adverse events (SAEs)

Timeframe: ICF signing to 90 days after last administration or initiation of new anti-tumor treatment

Trial details

NCT IDNCT05263271

SponsorChangchun GeneScience Pharmaceutical Co., Ltd.

Sponsor typeINDUSTRY

Study typeINTERVENTIONAL

Primary completion2024-12-02

View on ClinicalTrials.gov More Acute Myelogenous Leukemia trials

Plain-language summary

Who can participate

Age range18 Years – 75 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. The patient has the willingness to communicate with the Investigator, be able to understand and follow the trial requirements, volunteer to participate in the trial, understands and signs the written ICF, and is willing and able to comply with the visit schedule, administration plan, laboratory examination, and other clinical trial procedures.
✓. Gender: Male or female.
✓. Age ≥18
✓. Life expectancy ≥ 3 months.
✓. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
✓. Patients with relapsed/refractory AML or MDS for whom there exists no standard treatment options available.
✓. The white blood cell (WBC) count in the patient's peripheral blood must be ≤ 20 × 109/L within 7 days of the first dose of the study drug. The patients with WBC count \> 20 × 109/L may be treated with hydroxyurea (maximum dose 4 g/d) during the Screening period to achieve entry criteria. Hydroxyurea may be continued for the first 4 weeks of treatment (Cycle 1) to control blast counts at the discretion of the Investigator; hydroxyurea must be stopped after the first 4 weeks of treatment.
✓. Hb levels must be above 5 g/dL on the day of the first dose of the study drug, and may be maintained by transfusion. Transfusion is permitted in the duration of trial.

Gentulizumab in Relapsed/Refractory Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

Gentulizumab in Relapsed/Refractory Acute Myelogenous Leukemia or Myelodysplastic Syndrome

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

Exclusion criteria