Gene Therapy for Acute Lymphoblastic Leukemia

Recruiting at 7 trial locations

Overseen By Recruitment Partner: PatientWing

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Vironexis Biotherapeutics Inc.

Disqualifiers: Hepatoxicity, Thrombotic microangiopathy, Cardiomyopathy, others

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

Compensation: Varies

Number of Visits: Unknown

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy called VNX-101 for individuals with a type of blood cancer unresponsive to previous treatments. The goal is to determine if VNX-101 is safe and effective for people with CD19-positive blood cancers, such as certain leukemias and lymphomas. Suitable participants have leukemia or lymphoma that has recurred or resisted other treatments and possess a specific marker on the cancer cells called CD19. As a Phase 1 trial, participants will be among the first to receive this treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial protocol mentions that chemotherapy must be stopped within certain timelines, but it does not specify about other medications. It's best to discuss your current medications with the trial team to get a clear answer.

Is there any evidence suggesting that VNX-101 is likely to be safe for humans?

Research has shown that VNX-101, a gene therapy being tested for acute lymphoblastic leukemia, has promising safety results from early studies. Tests on mice and other animals demonstrated that a single dose of VNX-101 was safe, with no serious side effects. These animals also responded well, as the treatment effectively targeted the cancer cells. Additionally, the FDA approved the application to test VNX-101 in humans, indicating it is safe enough to start human trials. While these results are encouraging, it is important to remember that this treatment is still in the early stages of testing in people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard chemotherapy and targeted therapies for acute lymphoblastic leukemia, VNX-101 is a gene therapy that aims to change the game. Researchers are excited because VNX-101 uses a novel mechanism to alter specific genetic components in leukemia cells, potentially attacking the disease at its root. This approach could offer more precise targeting of cancer cells with fewer side effects, enhancing both effectiveness and quality of life for patients.

What evidence suggests that VNX-101 could be an effective treatment for acute lymphoblastic leukemia?

Research has shown that VNX-101, the investigational treatment in this trial, appears promising in early studies for treating CD19-positive acute lymphoblastic leukemia, a type of blood cancer. In animal tests, a single dose of VNX-101 was safe and successfully eliminated cancerous B cells. This treatment uses a virus to deliver a gene into the body, aiding the immune system in identifying and fighting leukemia cells. Initial results suggest this method could benefit patients with recurrent or difficult-to-treat leukemia. Although human studies have provided limited information, these early findings offer hope for its effectiveness. ^{1 2 3 4 5}

Who Is on the Research Team?

Vironexis Clinical Trials

Principal Investigator

Vironexis Biotherapeutics Inc.

Are You a Good Fit for This Trial?

This trial is for adults and teens with B-cell acute lymphoblastic leukemia that has come back or hasn't responded to treatment. They should have a certain amount of cancer cells in their bone marrow, can't be treated with CAR-T therapy or didn't improve after it, and must meet specific health criteria for major organs and blood.

Inclusion Criteria

My cancer cells are still CD19 positive after blinatumomab treatment.

AAVrh74 total antibody <1:400

Protocol-specified ranges for hematology parameters

Exclusion Criteria

History of hypersensitivity to corticosteroids or history of corticosteroid-related toxicity

I have moderate to severe acute GvHD or any grade of chronic GvHD.

Hepatoxicity (AST or ALT > 2x upper limit of normal)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-finding (Part 1)

Dose-finding PK study to determine the minimal dose that achieves target PK serum levels of GP101 at steady state without dose-limited toxicities

8 weeks

Treatment (Part 2)

Determine the safety and pharmacokinetics of VNX-101 at the recommended Part 2 dose in a broader array of subjects with higher leukemic burden

Up to 5 years

Long-term Follow-up

Long-term follow-up assessments for safety conducted post VNX-101 dosing

6 to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• VNX-101

Trial Overview

The study tests different doses of VNX-101, a gene therapy drug, to see how safe it is and how well it works against leukemia. It's an early-stage trial where patients receive increasing amounts of the drug to find the best dose.

How Is the Trial Designed?

Group I: Group 1/Group 2/Group 3/Group 4 Experimental Treatment 4 Interventions

Who Is Running the Clinical Trial?

Vironexis Biotherapeutics Inc.

Lead Sponsor

Trials

1

Recruited

30+

Published Research Related to This Trial

In a study of 135 children with newly diagnosed acute lymphoblastic leukemia (ALL), the PEG-Asp containing VDPAP regimen showed similar efficacy to the L-asparaginase containing VDLP regimen, with complete remission rates of 84.6% and 89.4%, respectively.

PEG-Asp demonstrated a longer half-life of about 7 days, providing a more prolonged therapeutic effect, while both regimens had comparable rates of adverse effects, primarily allergic reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of polyethylene glycol conjugated asparaginase and L-asparaginase for treatment of childhood acute lymphoblastic leukemia]. [2018]

Recent advancements in treating childhood acute lymphoblastic leukemia (ALL) have improved disease-free survival rates, particularly for high-risk groups, but ALL still remains the leading cause of cancer-related deaths in children.

Challenges persist in standardizing staging systems, ensuring adequate patient numbers for clinical studies, and accurately assessing treatment responses, which complicates the delivery of optimal therapy and supportive care for ALL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remaining problems in the staging and treatment of childhood lymphoblastic leukemia. Bleyer, WA.[2007]

A new 2-tier genetic classification for acute lymphoblastic leukemia (ALL) was developed using data from 809 patients, identifying good-risk (GR) and poor-risk (PR) genetic profiles based on specific genetic features.

Patients with a GR profile, which includes favorable genetic markers, showed a significantly higher event-free survival rate of 94% compared to 79% for those with a PR profile, indicating that genetic profiling can help tailor treatment intensity for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel integrated cytogenetic and genomic classification refines risk stratification in pediatric acute lymphoblastic leukemia. Moorman, AV., Enshaei, A., Schwab, C., et al.[2023]

Survival rates for acute lymphoblastic leukemia (ALL) in children have dramatically improved from about 10% in the 1960s to over 90% today, thanks to advancements in multi-agent chemotherapy, CNS prophylaxis, and supportive care.

Novel immunotherapies, such as blinatumomab and CAR T-cell therapy, have shown promise in treating relapsed or refractory B-ALL, offering better remission rates and lower toxicity compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA]. Elitzur, S., Izraeli, S.[2023]

The CCCG-ALL 2015 chemotherapy protocol for pediatric acute lymphoblastic leukemia (ALL) resulted in significantly lower rates of serious adverse events (SAE) and treatment-related mortality compared to the CCLG-ALL 2008 protocol, indicating a safer treatment option.

While the remission rates were similar between the two protocols, the CCCG-ALL 2015 group had a lower negative conversion rate of minimal residual disease (MRD), suggesting that while it is safer, its early efficacy in eliminating residual leukemia cells may need improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of the Early Efficacy and Serious Adverse Events between CCCG-ALL 2015 and CCLG-ALL 2008 in the Treatment of Pediatric Patients with Acute Lymphoblastic Leukemia]. Pan, LL., Zheng, YZ., LE, SH., et al.[2022]

The study demonstrated that using HIV-1-based lentiviral vectors can achieve over 90% gene transfer efficiency in B-precursor acute lymphoblastic leukemia (ALL) cell lines, indicating a highly effective method for engineering leukemia cells for immunotherapy.

Transduction of primary human B-precursor ALL cells also showed high efficiency with both MoMuLV-based retrovirus and HIV-1-based lentivirus vectors, suggesting potential for developing personalized immunotherapies for leukemia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene delivery to human B-precursor acute lymphoblastic leukemia cells. Mascarenhas, L., Stripecke, R., Case, SS., et al.[2021]

The combination of vincristine, dexamethasone, and L-asparaginase (VXL) showed synergistic effects in treating pediatric acute lymphoblastic leukemia (ALL) in both laboratory and mouse models, significantly delaying disease progression by up to 146 days.

Pharmacokinetic analysis indicated that the combination therapy increased the systemic exposure of dexamethasone, which may enhance the effectiveness of the treatment, providing a promising platform for testing new drugs in clinical trials for relapsed or refractory ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic modeling of an induction regimen for in vivo combined testing of novel drugs against pediatric acute lymphoblastic leukemia xenografts. Szymanska, B., Wilczynska-Kalak, U., Kang, MH., et al.[2021]

Recent advancements in the treatment of acute lymphoblastic leukemia (ALL) include the use of novel agents like blinatumomab, which have shown promising results in patients with relapsed/refractory disease and minimal residual disease (MRD).

The integration of targeted therapies, such as tyrosine kinase inhibitors for Philadelphia chromosome-like ALL and bcl-2/bcl-xl inhibitors for relapsed cases, is expected to enhance treatment outcomes and management strategies for ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Navigating the nexus of MRD and novel agents in ALL. Advani, AS., Copelan, EA.[2023]

Acute lymphoblastic leukemia (ALL) remains a leading cause of childhood cancer-related deaths, but advancements in treatment, including risk stratification based on early response, have improved outcomes significantly.

New immunotherapeutic approaches, such as monoclonal antibodies and gene-modified T cells, show promise in treating resistant cases of ALL and may be integrated with traditional chemotherapy to enhance cure rates while aiming to reduce treatment-related toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in the management of pediatric acute lymphoblastic leukemia. Starý, J., Hrušák, O.[2022]

The study found that Wnt16 does not activate canonical Wnt signaling in E2A-PBX1-positive B-ALL cells, despite high levels of Wnt16 and beta-catenin present in these cells.

Beta-catenin plays a crucial role in cell adhesion to the bone marrow stroma through N-cadherin, indicating that leukemia-stroma interactions may be mediated by this N-cadherin-dependent mechanism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

beta-catenin is involved in N-cadherin-dependent adhesion, but not in canonical Wnt signaling in E2A-PBX1-positive B acute lymphoblastic leukemia cells. Nygren, MK., Døsen-Dahl, G., Stubberud, H., et al.[2009]

The cure rate for childhood acute lymphoblastic leukemia (ALL) has surpassed 90% in recent clinical trials, but further improvements will depend on molecular therapies and precise risk stratification rather than just increasing chemotherapy doses.

Specific genetic markers, such as ETV6-RUNX1 and Philadelphia chromosome positivity, guide treatment decisions, with targeted therapies like dasatinib and venetoclax showing promise for high-risk subtypes, while innovative treatments like CAR-T cell therapy are being explored for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision medicine in acute lymphoblastic leukemia. Pui, CH.[2022]

3-5% of childhood acute lymphoblastic leukaemia (ALL) cases are linked to germline mutations, which can significantly impact treatment and necessitate genetic counseling for affected families.

Patients with ALL who have cancer predisposition mutations may face unique treatment challenges due to their reduced tolerance to chemotherapy and increased risk of organ toxicities, but many still have a good chance of being cured with appropriate chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related toxicities in children with acute lymphoblastic leukaemia predisposition syndromes. Schmiegelow, K.[2017]

Asparaginase is a crucial part of treatment for acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL), with pegaspargase being the preferred option due to its better pharmacokinetic profile and lower risk of immunogenic reactions compared to native E. coli asparaginase.

For patients who experience hypersensitivity reactions to asparaginase, switching to an Erwinia-derived formulation is recommended to maintain the benefits of treatment, highlighting the importance of managing side effects to ensure effective therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asparaginase therapy in patients with acute lymphoblastic leukemia: expert opinion on use and toxicity management. Sandley, M., Angus, J.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12341704/

Development of VNX-101, an adeno-associated virus with ...

A single dose of VNX-101 was safe in mice and non-human primates (NHPs) and eliminated B cell malignancies in xenograft models. Introduction. Outcomes for ...

2.

targetedonc.com

targetedonc.com/view/fda-clears-ind-of-vnx-101-in-cd19-acute-lymphoblastic-leukemia

FDA Clears IND of VNX-101 in CD19+ Acute ...

The investigational new drug application for VNX-101, a gene therapy aimed at treating CD19-positive acute lymphoblastic leukemia, has been approved by the FDA.

3.

healthtree.org

healthtree.org/all/community/articles/cd19-positive-all-treatment

The First Medication To Treat CD19+ Acute Lymphoblastic ...

... VNX-101, an “adeno-associated virus (AAV) vector-based gene therapy, enabling a phase 1/2 clinical trial in CD19+ acute lymphoblastic leukemia”.

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06533579

Study Details | NCT06533579 | Gene Therapy for CD19- ...

This is a Phase 1/2, first-in-human, open-label, dose-escalating trial designed to assess the safety and efficacy of VNX-101 in patients with relapsed or ...

5.

cgtlive.com

cgtlive.com/view/vironexis-biotherapeutics-aav-vector-based-immunotherapy-vnx-101-cleared-for-us-trial-in-acute-lymphoblastic-leukemia

Vironexis Biotherapeutics' AAV Vector-Based ... - CGTLive®

VNX-101 is intended to transduce cells of the liver, causing them to express a transgene coding for a bispecific T-cell engager.