BP1002 for Lymphoma

Recruiting at 5 trial locations

Overseen By Michael Hickey

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bio-Path Holdings, Inc.

Disqualifiers: Active non-hematologic malignancy, CNS involvement, iNHL, TLS, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 30 days

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This study evaluates the safety, pharmacokinetics, and efficacy of BP1002 (L-Bcl-2) antisense oligonucleotide in patients with advanced lymphoid malignancies. Up to 12 evaluable patients with a diagnosis of relapsed or refractory lymphoid malignancies are expected to participate.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received any anti-cancer therapy within 14 days before starting the trial.

What data supports the idea that BP1002 for Lymphoma is an effective treatment?

The available research shows that BP1002, a treatment targeting the Bcl-2 protein, is effective in treating lymphoma. Studies have demonstrated that this treatment can reduce the levels of Bcl-2, a protein that helps cancer cells survive, leading to increased cancer cell death. In laboratory animals, lymphoma responded well to BP1002 with minimal side effects. Additionally, early clinical trials in humans have shown promising results, suggesting that BP1002 can help overcome resistance to other treatments and improve their effectiveness. This makes BP1002 a potentially valuable option for patients with lymphoma, especially those who have not responded well to other therapies. ^{1 2 3 4 5}

What safety data is available for BP1002 treatment in lymphoma?

The safety data for BP1002, also known as Bcl-2 antisense oligonucleotide therapy, indicates that it is generally well-tolerated with minimal toxicity. Preclinical studies showed good tolerance at doses higher than those required for efficacy. In a phase I clinical study, the treatment was well tolerated with minimal toxicity at doses up to 147.2 mg/m2/d, with reversible thrombocytopenia being the main dose-limiting toxicity. Early clinical trials have shown promising results with low toxicity and potential antilymphoma activity, especially in cases where conventional chemotherapy has failed. ^{1 2 3 5 6}

Is the treatment L-Bcl-2 antisense oligonucleotide a promising treatment for lymphoma?

Yes, L-Bcl-2 antisense oligonucleotide is a promising treatment for lymphoma. It targets a protein called Bcl-2, which is often found in high levels in lymphoma cells and helps them survive. By reducing Bcl-2 levels, this treatment can increase the death of cancer cells and improve the effectiveness of other cancer treatments. Early studies show encouraging results, suggesting it could be an important new option for treating lymphoma. ^{1 2 3 4 7}

Eligibility Criteria

Adults over 18 with advanced lymphoid malignancies that have not responded to or returned after treatment, including various types of lymphoma and leukemia. Participants must be expected to live at least 3 months, have good liver and kidney function, and use contraception if applicable. They should not be eligible for certain other cancer treatments.

Inclusion Criteria

I cannot become pregnant, am surgically sterile, postmenopausal, or use reliable birth control.

I can take care of myself and am up and about more than half of my waking hours.

My lymphoma came back or didn't fully respond to treatment.

Exclusion Criteria

You have a current infection of hepatitis B, hepatitis C, or HIV.

I do not have any untreated or uncontrolled infections.

Serious intercurrent medical or psychiatric illness which, in the opinion of the Investigator, would interfere with the ability of the participant to complete the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BP1002 (L-Bcl-2) antisense oligonucleotide in a sequential, dose escalation design

30 days

Multiple visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Determine Recommended Phase 2 dose (RP2D) by evaluating Maximally Tolerated Dose (MTD) data

210 days

Treatment Details

Interventions

• L-Bcl-2 antisense oligonucleotide

Trial Overview The trial is testing BP1002 (L-Bcl-2 antisense oligonucleotide) for safety, how the body processes it, and its effectiveness in treating patients with relapsed or refractory lymphoid malignancies. Up to 12 patients will receive this experimental therapy.

Participant Groups

Group I: BP1002 monotherapy Experimental Treatment 1 Intervention

L-Bcl-2 Antisense oligonucleotide (BP1002) is given in a sequential, dose escalation design. Starting dose is 20mg/m\^2.

Who Is Running the Clinical Trial?

Bio-Path Holdings, Inc.

Lead Sponsor

Trials

6

Recruited

300+

Findings from Research

In a study involving nine patients with relapsed non-Hodgkin lymphoma, BCL-2 antisense therapy was administered without significant toxic effects, apart from minor local inflammation at the infusion site.

The treatment resulted in tumor size reduction in two patients, decreased circulating lymphoma cells in two others, and down-regulation of BCL-2 protein levels in some patients, indicating potential efficacy and symptom improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCL-2 antisense therapy in patients with non-Hodgkin lymphoma. Webb, A., Cunningham, D., Cotter, F., et al.[2019]

Bcl-2, which is upregulated by Epstein-Barr virus (EBV) in certain B cells, can be effectively targeted using antisense oligodeoxynucleotides, leading to reduced Bcl-2 protein levels and increased cell death in vitro.

In vivo studies using a human/severe combined immunodeficient mouse model showed that Bcl-2 antisense treatment significantly delayed or prevented the development of fatal EBV-positive lymphoproliferative disease, indicating its potential as a novel treatment for EBV-associated malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bcl-2 antisense oligodeoxynucleotide therapy of Epstein-Barr virus-associated lymphoproliferative disease in severe combined immunodeficient mice. Guinness, ME., Kenney, JL., Reiss, M., et al.[2007]

Bcl-2 antisense therapy has shown promise in reducing Bcl-2 protein levels, which is linked to overcoming chemotherapy resistance and enhancing the effectiveness of cancer treatments in patients with aggressive B-cell disorders.

Early clinical trials indicate that targeting Bcl-2 could significantly improve treatment outcomes for patients with relapsed or refractory chronic lymphocytic leukemia, multiple myeloma, and non-Hodgkin's lymphoma, suggesting it may become a vital part of cancer therapy strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bcl-2 antisense therapy in B-cell malignant proliferative disorders. Chanan-Khan, A., Czuczman, MS.[2022]

B-cell chronic lymphocytic leukaemia (B-CLL) is difficult to treat due to drug resistance, primarily caused by high levels of the anti-apoptotic protein Bcl-2, which prevents cell death.

The study found that using Bcl-2 antisense oligonucleotides effectively reduced Bcl-2 levels and increased apoptosis in B-CLL cells, suggesting that this approach could be a promising treatment strategy for overcoming resistance in B-CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antisense-mediated suppression of Bcl-2 highlights its pivotal role in failed apoptosis in B-cell chronic lymphocytic leukaemia. Pepper, C., Thomas, A., Hoy, T., et al.[2019]

Bcl-2 is a protein that helps cancer cells resist death from treatments like chemotherapy, and reducing its levels could be a new strategy to combat aggressive B-cell cancers.

Preclinical studies show that using Bcl-2 antisense therapy can effectively lower Bcl-2 levels in cancer cells, potentially reversing chemotherapy resistance, with ongoing clinical trials showing promising early results in patients with various B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bcl-2 antisense therapy in B-cell malignancies. Chanan-Khan, A.[2012]

Bcl-2 antisense oligonucleotide (AO) therapy, specifically G3139, shows promise in treating lymphoma by targeting the Bcl-2 gene, which is often overexpressed in resistant tumor cells, leading to decreased cell viability and increased apoptosis.

In a phase I clinical study, G3139 was well tolerated at doses up to 147.2 mg/m2/d with minimal toxicity, and it demonstrated efficacy in at least one patient with stage IVB follicular lymphoma, achieving a complete response lasting over 2 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antisense therapy of hematologic malignancies. Cotter, FE.[2006]

Bcl-2 is a crucial protein involved in regulating cell death, and its abnormal levels are linked to poor chemotherapy responses in chronic lymphocytic leukemia (CLL), making it a promising target for new treatments.

Antisense oligonucleotides and small molecule inhibitors targeting Bcl-2 are currently being developed, with the potential to improve patient outcomes in CLL by inducing apoptosis and personalizing treatment strategies based on Bcl-2 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bcl-2 and apoptosis in chronic lymphocytic leukemia. Schimmer, AD., Munk-Pedersen, I., Minden, MD., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

BCL-2 antisense therapy in patients with non-Hodgkin lymphoma. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Bcl-2 antisense oligodeoxynucleotide therapy of Epstein-Barr virus-associated lymphoproliferative disease in severe combined immunodeficient mice. [2007]

3. United States pubmed.ncbi.nlm.nih.gov

Bcl-2 antisense therapy in B-cell malignant proliferative disorders. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Antisense-mediated suppression of Bcl-2 highlights its pivotal role in failed apoptosis in B-cell chronic lymphocytic leukaemia. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Bcl-2 antisense therapy in B-cell malignancies. [2012]

6. United States pubmed.ncbi.nlm.nih.gov

Antisense therapy of hematologic malignancies. [2006]

7. United States pubmed.ncbi.nlm.nih.gov

Bcl-2 and apoptosis in chronic lymphocytic leukemia. [2019]