LBS-007 for Acute Leukemia

Recruiting at 8 trial locations

Overseen By Lin BioScience Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Lin BioScience, Inc

Must not be taking: Chemotherapy, Immunotherapy, others

Disqualifiers: CNS involvement, Other malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

90 Participants Needed

Trial Summary

What is the purpose of this trial?

The most common types of acute leukaemia are acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML). AML is a heterogenous clonal disorder of haemopoietic progenitor cells and the most common and severe malignant leukemia in adults and is responsible for the highest mortality from leukemia. ALL is a neoplasm characterized by the growth of malignant lymphoblasts of the B or T lineage, leading to an inhibition of proliferation of the normal blood cell lineages. The primary objectives of this study are investigating the safety, tolerability, and the MTD of LBS-007. The secondary objectives are to assess the efficacy and to determine the pharmacokinetics (PK) of LBS-007. The exploratory objective is to study and correlate the changes in surrogate biomarkers in response to treatment.

Will I have to stop taking my current medications?

The trial requires that you do not take other chemotherapy, radiation therapy, or immunotherapy while participating. If you are on these treatments, you will need to stop them before joining the trial.

What makes the drug LBS-007 unique for treating acute leukemia?

LBS-007 may be unique due to its potential to enhance the immune response against leukemia cells, possibly involving mechanisms similar to those seen with B7 molecules and interleukin 7 (IL-7), which are known to boost immune activity in leukemia. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults over 18 with relapsed or resistant acute leukemias like AML or ALL, who can't have standard treatments anymore. They should be relatively active and able to do light activities (ECOG status 0-2).

Inclusion Criteria

I am over 18 years old.

My leukemia has come back or didn't respond to treatment.

I have no standard treatment options left that could cure or significantly control my disease.

Exclusion Criteria

I am not currently receiving chemotherapy, radiation, or immunotherapy.

I have leukemia affecting my brain or spinal cord.

I haven't had any cancer besides basal cell skin cancer or any cancer treated and cured in the last 2 years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

Phase 1: Dose finding phase to evaluate LBS-007 as a monotherapy and combination with Venetoclax and Azacitidine

Variable duration

Dose Expansion

Phase 2: Dose expansion phase to evaluate LBS-007 as a monotherapy and combination therapy at the optimal dose identified by phase 1

Variable duration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• LBS-007

Trial Overview The study tests the safety and maximum tolerated dose of a new drug called LBS-007 in patients with acute leukemia. It also looks at how well it works and measures how the body processes it.

Participant Groups

Group I: Dose Finding and Expansion Phase Experimental Treatment 1 Intervention

Phase 1: Dose finding phase to evaluate LBS-007 as a monotherapy and combination with Venetoclax and Azacitidine Phase 2: Dose expansion phase to evaluate LBS-007 as a monotherapy and combination therapy at the optimal dose identified by phase 1 (dose finding)

LBS-007 is already approved in United States for the following indications:

Approved in United States as LBS-007 for:

• Acute Lymphoblastic Leukemia (ALL)
• Acute Myeloid Leukemia (AML)

Who Is Running the Clinical Trial?

Lin BioScience, Inc

Lead Sponsor

Trials

1

Recruited

90+

Lin BioScience Pty Ltd

Collaborator

Trials

1

Recruited

90+

Findings from Research

The B7-1 vaccine, developed by introducing the B7-1 gene into L615 leukemic cells, showed promise in inducing an immune response against leukemic cells, as evidenced by the selection of a highly expressing clone (L615-B7).

In vitro studies demonstrated that L615-B7 cells enhanced T cell functions, including cytotoxicity, proliferation, and growth factor secretion, indicating a potential mechanism for the vaccine's immunoprotective effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experimental study of anti-tumor immunity induced by B7 vaccine of a highly malignant murine leukemic T cell line (L615)]. Li, M., You, S., Liao, X.[2017]

The BRD7 gene is significantly up-regulated in bone marrow mononuclear cells from patients with acute leukemia, suggesting its potential role in the disease's pathology.

Two specific single nucleotide polymorphisms (C495T and A737G) in the BRD7 gene are associated with acute leukemia, indicating that these genetic variations may contribute to the susceptibility to the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Expression and SNP analysis of BRD7 gene in acute leukemia cells]. Tang, XY., Liu, F., Peng, Y., et al.[2008]

In a study of 30 untreated adult patients with CD7 positive acute myeloid leukemia (CD7+ AML), it was found that these patients often exhibited higher levels of leukocytosis and were more likely to express CD34 and P-glycoprotein.

Only 42.3% of CD7+ AML patients achieved complete remission, with a median remission duration of just 4 months, indicating a poorer prognosis compared to other AML subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunophenotype and P-glycoprotein expression in CD7 positive adult acute myeloid leukemia]. Hua, D., Li, J., Xia, X.[2018]

In a study of 410 acute leukemia patients, 7.8% exhibited abnormalities of chromosome 7, with the most common being -7/7q-; this anomaly was particularly prevalent in certain subtypes of acute myeloid leukemia (M0, M1, and M2).

Patients with chromosome 7 anomalies had a lower complete remission rate (36.7%) after chemotherapy compared to the overall acute leukemia population (65.8%), indicating that these chromosomal abnormalities are linked to a poorer prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analysis of 32 cases of acute leukemia with abnormality of chromosome 7]. Lu, Y., Jin, J., Chen, ZM., et al.[2015]

Interleukin 7 (IL-7) significantly enhances the expression of B7-1 and B7-2 molecules on acute leukemia (AL) cells, which are important for immune response, indicating a potential mechanism for improving immunogenicity in leukemia treatment.

IL-7-treated leukemia cells can stimulate the proliferation of allogeneic peripheral blood mononuclear cells (PBMNC) and increase their production of interferon-gamma (IFN-gamma), suggesting that IL-7 may enhance the immune response against leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Study on the up-regulation of B7 molecules expression and immunogenicity of acute leukemia cells induced by interleukin 7]. Qian, WB., Lin, MF.[2017]

References

1. China pubmed.ncbi.nlm.nih.gov

[Experimental study of anti-tumor immunity induced by B7 vaccine of a highly malignant murine leukemic T cell line (L615)]. [2017]

2. China pubmed.ncbi.nlm.nih.gov

[Expression and SNP analysis of BRD7 gene in acute leukemia cells]. [2008]

3. China pubmed.ncbi.nlm.nih.gov

[Immunophenotype and P-glycoprotein expression in CD7 positive adult acute myeloid leukemia]. [2018]

4. China pubmed.ncbi.nlm.nih.gov

[Analysis of 32 cases of acute leukemia with abnormality of chromosome 7]. [2015]

5. China pubmed.ncbi.nlm.nih.gov

[Study on the up-regulation of B7 molecules expression and immunogenicity of acute leukemia cells induced by interleukin 7]. [2017]