BTM-3566 for B-Cell Lymphoma

Overseen By Meghan Reynolds

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Bantam Pharmaceuticals

Disqualifiers: Primary CNS lymphoma, Neurologic disease, Second malignancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 24 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, BTM-3566, to determine its effectiveness in treating mature B-cell lymphoma that has returned or resisted previous treatments. Researchers aim to identify the optimal dose, assess side effects, and evaluate the drug's ability to slow or halt cancer progression. Participants will take the drug in 14-day cycles and attend regular clinic visits to monitor progress. This trial may suit adults with relapsed or resistant mature B-cell lymphoma who meet specific health criteria. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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

The trial information does not specify if you need to stop taking your current medications. However, it does mention that you cannot have received any anti-cancer therapy within 28 days before starting the trial.

Is there any evidence suggesting that BTM-3566 is likely to be safe for humans?

Research has shown that BTM-3566 is being tested for safety in individuals with certain types of B-cell lymphoma. Earlier lab tests found that BTM-3566 kills cancer cells quickly, suggesting potential effectiveness. However, the current focus remains on ensuring its safety.

As BTM-3566 is in early testing stages, limited information exists on human reactions. The current trial aims to identify potential side effects and understand how the body processes the drug over time. The goal is to determine the safest dose by closely monitoring participants for any adverse reactions.

No information is available yet on BTM-3566's effects outside clinical trials, but the research is carefully controlled to ensure safety. Participants will undergo regular checkups and tests to confirm the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

BTM-3566 is unique because it offers a new approach to treating B-cell lymphoma by being administered as an oral solution, which is different from the more common intravenous treatments like rituximab or chemotherapy. This oral delivery method could make treatment more convenient and less invasive for patients. Researchers are also intrigued by BTM-3566's potential new mechanism of action, which may target cancer cells more precisely, potentially leading to better outcomes and fewer side effects.

What evidence suggests that BTM-3566 might be an effective treatment for B-cell lymphoma?

Research has shown that BTM-3566, the investigational treatment in this trial, may help treat B-cell lymphomas. In earlier studies, this treatment successfully killed cancer cells in the lab, particularly in diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). BTM-3566 works by rapidly inducing cancer cell death, with noticeable effects within 24 hours in lab tests. The compound is especially effective against high-risk lymphoma types, which are often more challenging to treat. These findings suggest that BTM-3566 could be a strong option for patients with relapsed or hard-to-treat B-cell lymphomas. ^{2 3 6 7 8}

Who Is on the Research Team?

Zahid Bashir, MBBS

Principal Investigator

Bantam Pharmaceuticals

Are You a Good Fit for This Trial?

Adults over 18 with relapsed or refractory mature B cell lymphoma can join this trial. They should have measurable disease, be able to perform daily activities (ECOG PS 0-2), and likely live at least another 3 months. Participants must use birth control during the study and for 90 days after.

Inclusion Criteria

Must have measurable disease per response evaluation criteria in lymphoma (Lugano classification)

Must have a predicted life expectancy of ≥3 months

Must agree to use adequate birth control throughout their participation and for 90 days following the last dose of BTM-3566

Exclusion Criteria

Is pregnant or breastfeeding

I have been diagnosed with lymphoma in my brain or spinal cord.

I have side effects from cancer treatment that are mild or worse.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-3 weeks

Treatment

Participants receive BTM-3566 in 14-day cycles with 7 days of dosing followed by 7 days off

24 months

Regular clinic visits for checkups and tests

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Imaging every 3 months, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• BTM-3566

Trial Overview The trial is testing BTM-3566's safety and effectiveness in treating mature B cell lymphomas that have come back or didn't respond to treatment. It involves taking the drug for a week, then pausing for a week, while attending regular clinic visits and tracking dosing.

How Is the Trial Designed?

Group I: BTM-3566 Treatment Experimental Treatment 1 Intervention

BTM-3566 Oral Solution

Who Is Running the Clinical Trial?

Bantam Pharmaceuticals

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

New-generation Bruton tyrosine kinase inhibitors (BTKi) show a high overall response rate of 92% in treating chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), particularly benefiting younger patients and those receiving combination therapy.

While BTKi-based therapies are generally well-tolerated, they can lead to significant adverse events like cytopenia and hypertension, and zanubrutinib may offer better efficacy than acalabrutinib as a monotherapy for CLL/SLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of new-generation Bruton tyrosine kinase inhibitors in chronic lymphocytic leukemia/small lymphocytic lymphoma: a systematic review and meta-analysis. Yin, S., Zheng, X., Zhang, W., et al.[2023]

A novel B-cell lymphoma cell line, YM, was established from a patient with diffuse large cell lymphoma, showing rearrangements of the BCL2 and BCL6 genes, which are implicated in the development of non-Hodgkin's lymphoma.

The YM cells exhibited both t(2;18) and t(3;16) translocations, leading to deregulated overexpression of BCL2 and BCL6, suggesting a potential collaboration between these genes in the pathogenesis of B-cell non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular features of a new human lymphoma cell line carrying both BCL2 and BCL6 gene rearrangements. Yonetani, N., Akasaka, T., Akasaka, H., et al.[2015]

A systematic review of 55 studies found that first-generation BTK inhibitors had a significantly higher incidence of cardiovascular adverse events (20.8%) compared to second-generation BTK inhibitors (6.3%).

While second-generation BTK inhibitors showed lower cardiovascular risks, they were associated with higher rates of hematologic/oncologic (62.3% vs. 39.2%) and gastrointestinal side effects (36.9% vs. 28.9%) compared to first-generation inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of Bruton's tyrosine kinase inhibitors in B-cell malignancies: A systematic review. Arustamyan, M., Kibrik, P., Hatipoglu, D., et al.[2022]

The BCH-LBL-2003 treatment regimen, modified from the BFM-90 protocol, showed high efficacy in treating childhood lymphoblastic lymphoma, achieving a 100% overall response rate and a 5-year overall survival rate of 87% among 112 patients studied over a median follow-up of 29 months.

Despite the high effectiveness, all patients experienced significant hematological toxicity (grade 3-4), and certain factors such as lack of complete remission at the end of induction therapy and T-cell immunophenotype were identified as poor prognostic indicators.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical features and prognosis of children with lymphoblastic lymphoma]. Jin, L., Zhang, R., Huang, S., et al.[2018]

In a phase I trial involving 18 patients with advanced B-cell malignancies, the BTK inhibitor M7583 showed a 50% objective response rate and a 78% disease control rate, indicating promising efficacy for patients who had failed prior treatments.

The drug was well tolerated, with no dose-limiting toxicities reported, although 89% of patients experienced treatment-emergent adverse events, primarily diarrhea, fatigue, and vomiting, suggesting a favorable safety profile for further testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I, first-in-human trial of Bruton's tyrosine kinase inhibitor M7583 in patients with B-cell malignancies. Jurczak, W., Rule, S., Townsend, W., et al.[2021]

The modified B-NHL-BFM-90 protocol resulted in an 83% complete remission rate among 55 Chinese children and adolescents with Burkitt's lymphoma and large cell lymphoma, indicating high efficacy in treating these conditions.

The event-free survival rate was 85% at a median follow-up of 24 months, with manageable side effects like myelosuppression and mucositis, suggesting the treatment is both effective and tolerable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved treatment outcome in Chinese children and adolescents with Burkitt's lymphoma and large cell lymphoma by using the modified B-non-Hodgkin's lymphoma-Berlin-Frankfurt-Münster-90 protocol. Sun, XF., Zhen, ZJ., Lui, DG., et al.[2015]

BCL6 is a key protein involved in the development of germinal centers and is often mutated in B cell non-Hodgkin lymphomas (B-NHL), making it a promising target for therapy.

Several agents that inhibit BCL6 have shown anti-lymphoma activity in preclinical models, and future clinical trials will be crucial to assess their efficacy in treating B-NHL, especially when used alongside other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCL6 as a therapeutic target for lymphoma. Leeman-Neill, RJ., Bhagat, G.[2018]

BCL6 is a crucial transcription factor in B-cell and T-cell functions, playing a significant role in various lymphomas, including diffuse large B-cell lymphoma (DLBCL), where it is linked to better treatment responses.

Recent development of BCL6 antagonists shows promise, as they can inhibit the survival of DLBCL cells that rely on BCL6, suggesting potential for new lymphoma treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of BCL6 in lymphomas and routes to therapy. Wagner, SD., Ahearne, M., Ko Ferrigno, P.[2016]

BCL6 rearrangements were identified in 35.5% of diffuse large cell lymphomas (DLLC), indicating a significant genetic alteration associated with this type of cancer.

This genetic change was most common in diffuse large cell lymphoma (45%) compared to other types of non-Hodgkin's lymphoma, suggesting that BCL6 could be a key factor in understanding the development and monitoring of DLLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rearrangements of the BCL6 gene in diffuse large cell non-Hodgkin's lymphoma. Lo Coco, F., Ye, BH., Lista, F., et al.[2021]

Disulfide (DSF), especially in combination with copper (Cu), significantly inhibits the growth of diffuse large B-cell lymphoma (DLBCL) cells by inducing apoptosis and causing cell cycle arrest, as demonstrated in four DLBCL cell lines and primary cells from eight patients.

The mechanism of action involves the inhibition of the NF-κB signaling pathway and a reduction in BCL6 levels, suggesting that DSF has therapeutic potential for treating DLBCL, which is typically resistant to conventional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DSF/Cu induces antitumor effect against diffuse large B-cell lymphoma through suppressing NF-κB/BCL6 pathways. Zhu, Y., Lei, C., Jiang, Q., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS7097

A phase 1 trial of BTM-3566 in relapsed/refractory mature B ... BTM-3566, a novel compound demonstrated efficacy against diverse B-cell malignancies, with the most pronounced impact observed in DLBCL and MCL.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06792734

Study Details | NCT06792734 | Phase 1 Trial of BTM-3566 ... It will also learn how well BTM-3566 works to treat relapsed or refractory mature b cell lymphomas. The main questions it aims to answer are:

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10723637/

Targeting Aggressive B-cell Lymphomas through ... BTM-3566 induced rapid apoptosis in lymphoma lines, with nearly complete killing at 24 hours (Fig. 1D; Supplementary Fig. S1A), whereas the inactive compound ...

4. synapse.patsnap.com synapse.patsnap.com/article/unlocking-the-potential-of-btm-3566-a-breakthrough-in-mitochondrial-stress-response-for-diffuse-large-b-cell-lymphoma-therapy

Unlocking the Potential of BTM-3566: A Breakthrough in ... It induces apoptosis and cell death in DLBCL lines with an IC50 of ~200 - 500 nM, affecting ABC, GCB, and high-risk lymphoma lines.

5. nature.com nature.com/articles/d43747-023-00075-3

The good kind of stress In humans, mantle cell lymphoma and diffuse large B cell lymphoma (DLBCL) are very likely to respond to BTM-3566, especially double- and triple-hit DLBCL. ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06792734

Study Details | NCT06792734 | Phase 1 Trial of BTM-3566 ... The goal of this clinical trial is to learn if BMT-3566 can safety be given to adult patients with relapsed or refractory mature b cell lymphomas. It will ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121026744

Btm-3566, a Novel Activator of the Mitochondrial Stress ... BTM-3566 is an oral small molecule based on a pyrazolothiazol-backbone, developed for treatment of diffuse large B-cell lymphoma (DLBCL).

8. isrctn.com isrctn.com/pdf/15438979

An early phase trial to test the safety and determine the ... ... BTM-3566 in Relapsed/Refractory Mature B Cell Lymphomas. Study objectives. To determine the dose-limiting toxicity and safety of BTM-3566.