BP1002 for Lymphoma

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BP1002 (L-Bcl-2 antisense oligonucleotide), designed to help people with certain types of lymphoma that have returned or resisted previous treatments. The main goal is to determine BP1002's safety and its effects in the body. Suitable candidates for this trial have tried at least three other treatments without success and are dealing with specific lymphomas like DLBCL, Mantle Cell Lymphoma, or Hodgkin Lymphoma, among others. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that BP1002 is likely to be safe for humans?

Research has shown that the L-Bcl-2 antisense oligonucleotide, used in BP1002, holds promise in early studies. In lab research, scientists tested this treatment on mice with lymphoma, a type of blood cancer. The results indicated that it slowed tumor growth, suggesting it might have a similar effect in humans, although more research is needed.

As this is an early-phase study, the main focus is on safety and understanding how the body processes the treatment. Consequently, there is limited information on tolerance or potential side effects. Safety data from this phase will be crucial for understanding its effects in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Most treatments for lymphoma, like chemotherapy and targeted therapy, work by attacking cancer cells directly or disrupting their growth signals. But BP1002 introduces a novel approach by using an L-Bcl-2 antisense oligonucleotide to specifically block the Bcl-2 protein, which helps cancer cells survive. This unique mechanism of action could potentially make BP1002 more effective in targeting cancer cell survival pathways, offering hope for a new option in the fight against lymphoma.

What evidence suggests that BP1002 might be an effective treatment for lymphoma?

Research has shown that L-Bcl-2, a type of genetic material, can slow the growth of lymphoma cells, a kind of cancer. Lab studies demonstrated that it reduced the spread of these cancer cells, indicating potential as a treatment. This trial will evaluate L-Bcl-2 as a monotherapy. Earlier studies on similar therapies showed improvements in symptoms and tumor responses in patients. These findings suggest that L-Bcl-2 could be a promising option for treating advanced lymphoid cancers. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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, 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04072458

NCT04072458 | A Clinical Trial of BP1002 in Patients With ... This study evaluates the safety, pharmacokinetics, and efficacy of BP1002 (L-Bcl-2) antisense oligonucleotide in patients with advanced lymphoid ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8778715/

Making Sense of Antisense Oligonucleotide Therapeutics ... Similarly, L-Bcl-2 decreased proliferation of lymphoma cells lines [104]. Combination treatments of L-Bcl-2 with ara-C also proficiently induced ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04072458/a-clinical-trial-of-bp1002-in-patients-with-advanced-lymphoid-malignancies

A Clinical Trial of BP1002 in Patients With Advanced ... This study evaluates the safety, pharmacokinetics, and efficacy of BP1002 (L-Bcl-2) antisense oligonucleotide in patients with advanced lymphoid malignancies.

4. aacrjournals.org aacrjournals.org/clincancerres/article/7/2/400/288422/Efficacy-of-Treatment-with-Antisense

Efficacy of Treatment with Antisense Oligonucleotides ... Quantitation confirms the Western blot data that AS cμ oligonucleotide treatment of mice leads to reduced bcl-2 protein levels in lymphoma cells in the spleen ( ...

5. thelancet.com thelancet.com/journals/lancet/article/PIIS014067369611103X/abstract

BCL-2 antisense therapy in patients with non-Hodgkin ... BCL-2 antisense therapy led to an improvement in symptoms, objective biochemical and radiological evidence of tumour response, and down-regulation of the BCL-2 ...

6. aacrjournals.org aacrjournals.org/cancerres/article/80/16_Supplement/CT240/645060/Abstract-CT240-A-phase-I-clinical-trial-to-study

Abstract CT240: A phase I clinical trial to study the safety ... Preclinical studies showed that L-Bcl-2 inhibited Bcl-2 protein expression and in vivo tumor growth. Bcl-2 expression is frequently altered in ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-08724

A Clinical Trial of BP1002 in Patients With Advanced ... This study evaluates the safety, pharmacokinetics, and efficacy of BP1002 (L-Bcl-2) antisense oligonucleotide in patients with advanced lymphoid malignancies.

8. clin.larvol.com clin.larvol.com/trial-detail/NCT04072458

A Clinical Trial of BP1002 in Patients With Advanced ... Title: The combination of liposomal Bcl-2 antisense oligonucleotide (BP1002) with decitabine is efficacious in venetoclax-resistant cells.” GlobeNewswire 2020 - ...