BMF-500 for Leukemia

Not currently recruiting at 27 trial locations

Overseen By Steve Morris, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Biomea Fusion Inc.

Must be taking: Azole antifungals

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Cardiovascular disease, High WBC, Pregnancy, others

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

Compensation: Varies

Number of Visits: 56

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BMF-500 for adults with acute leukemia, a type of blood cancer. Researchers aim to determine the best dose and assess its effectiveness in individuals with specific gene mutations, particularly the FLT3 mutation. The trial includes different groups based on the medications participants take alongside BMF-500. Eligible participants should have relapsed or hard-to-treat acute leukemia and meet certain health criteria, such as good liver and kidney function. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that participants in Arm A stop taking moderate or strong CYP3A4 inhibitors at least 7 days before joining and avoid them for at least 4 weeks. Participants in Arm B must continue taking a necessary azole antifungal that is a moderate or strong CYP3A4 inhibitor for at least 4 weeks.

Is there any evidence suggesting that BMF-500 is likely to be safe for humans?

Research has shown that BMF-500, a treatment being tested for leukemia, has been safe so far. In studies with previous patients, researchers found no serious side effects that would prevent dose escalation. This indicates that patients tolerated the treatment well at various dose levels.

As the treatment remains in the early stages, researchers are primarily focused on determining the right dose. However, the lack of severe side effects in early testing is a positive indicator of its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for leukemia, like chemotherapy and targeted therapies, work by killing rapidly dividing cells or targeting specific genetic mutations. But BMF-500 works differently, as it is designed to be effective even when used alongside drugs that affect CYP3A4 enzyme activity. Researchers are excited about BMF-500 because it offers flexibility in dosing for patients who are on other medications that can interfere with treatment. This could mean more personalized therapy options and improved outcomes for patients with leukemia.

What evidence suggests that BMF-500 might be an effective treatment for leukemia?

Research shows that BMF-500, a pill targeting a specific protein, may help treat acute leukemia. Studies have found that BMF-500 significantly improves the bone marrow of patients with a certain type of acute myeloid leukemia (AML), a blood cancer. It continues to kill cancer cells even after the drug leaves the body. Additionally, patients taking BMF-500 have lived longer than average compared to past data. These early findings suggest that BMF-500 could effectively treat certain types of acute leukemia. Participants in this trial will receive BMF-500 in different contexts, depending on their use of azole antifungals, to evaluate its effectiveness and safety. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

Adults over 18 with acute leukemia (AML, ALL, or MPAL) that has come back or didn't respond to treatment. They must have a FLT3 mutation and be able to follow rules about using certain other drugs. People can't join if they have very high white blood cell counts, serious heart problems, recent strokes, or are pregnant.

Inclusion Criteria

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

My liver and kidneys are working well.

My leukemia has returned or is not responding to treatment, and I have a FLT3 mutation.

Exclusion Criteria

My white blood cell count is over 50,000 and cannot be controlled with treatment.

I haven't had major heart problems or strokes in the last 6 months.

I am not pregnant, breastfeeding, nor planning to become pregnant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation

Participants receive BMF-500 in a dose-escalation format to determine the recommended Phase 2 Dose (RP2D)

28 days per cycle, up to 32 cycles

Visits at the end of each 28-day cycle

Dose-expansion

Participants receive BMF-500 in a dose-expansion format to further evaluate safety and efficacy

28 days per cycle, up to 32 cycles

Visits at the end of each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BMF-500

Trial Overview The trial is testing BMF-500, an oral drug for acute leukemia targeting the FLT3 gene mutation. It's a first-in-human study where doses will gradually increase to find safe levels before expanding to more patients.

How Is the Trial Designed?

Group I: Arm C: Escalation Phase Experimental Treatment 1 Intervention

BMF-500 taken twice daily by participants who are receiving necessary azole antifungals that are moderate CYP3A4 inhibitors.

Group II: Arm B: Escalation Phase Experimental Treatment 1 Intervention

BMF-500 taken twice daily by participants who are receiving necessary azole antifungals that are Strong CYP3A4 inhibitors.

Group III: Arm A: Escalation Phase Experimental Treatment 1 Intervention

BMF-500 taken twice daily by participants who are not receiving drugs that inhibit CYP3A4 activity.

Who Is Running the Clinical Trial?

Biomea Fusion Inc.

Lead Sponsor

Trials

5

Recruited

780+

Published Research Related to This Trial

The addition of granulocyte colony-stimulating factor (G-CSF) to chemotherapy significantly improves overall survival (OS) and disease-free survival (DFS) in patients with acute myeloid leukemia (AML), particularly in those who have not received prior treatment.

For patients with relapsed or refractory AML, G-CSF did not show a significant benefit in survival or remission rates compared to those not receiving G-CSF, indicating its effectiveness may be limited to earlier stages of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact on acute myeloid leukemia relapse in granulocyte colony-stimulating factor application: a meta-analysis. Feng, X., Lan, H., Ruan, Y., et al.[2018]

Myeloid growth factors, such as granulocyte-colony stimulating factors, are safe and well-tolerated in patients with acute leukemias, effectively reducing the duration of neutropenia during chemotherapy.

While these growth factors help shorten neutropenia and improve disease-free survival in some patients, they do not significantly impact overall survival or complete remission rates in acute myeloid and lymphoblastic leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of myeloid growth factors in acute leukemia. Wadleigh, M., Stone, RM.[2019]

Bone marrow fibroblasts (BMF) from leukemia patients can inhibit the proliferation of leukemic cells, showing both direct effects and those mediated by autocrine signaling.

The effectiveness of BMF in inhibiting leukemic cell growth varies based on the specific type of leukemia and the cell line tested, indicating that the disease context and cellular interactions play significant roles in this process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of media conditioned with bone marrow fibroblasts on proliferation of leukemic blast cell lines]. Maliulaĭtene, ER., Blagosklonnyĭ, MV.[2020]

Bone marrow fibroblasts (BMF) from normal adults and patients in complete remission (CR) enhanced the growth of colony-forming units in culture (CFU-C), while BMF from patients with acute leukemia (AL) at diagnosis did not support this growth, indicating a potential impairment in the bone marrow microenvironment during active disease.

BMF from patients with AL at diagnosis exhibited a significantly higher inhibitory effect on CFU-C growth compared to BMF from normal subjects, suggesting that the disease state alters the supportive role of bone marrow fibroblasts in hematopoiesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abnormal regulation of granulopoiesis by bone marrow fibroblasts in leukemia. Shimizu, M., Nagao, T., Arimori, S.[2004]

B-lineage acute lymphoblastic leukemia (ALL) cells, both Philadelphia chromosome-positive and negative, universally express the BAFF-R receptor, which is crucial for their survival and growth, indicating a potential target for therapy.

Stimulation of BAFF-R not only activates survival pathways in ALL cells but also protects them from apoptosis induced by nilotinib, suggesting that blocking BAFF-R could enhance treatment effectiveness in ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A functional receptor for B-cell-activating factor is expressed on human acute lymphoblastic leukemias. Parameswaran, R., Müschen, M., Kim, YM., et al.[2021]

In a study of 473 children with acute myeloid leukemia (AML), 88% achieved remission, and the 5-year overall survival rate improved from 58% to 62% compared to previous trials, indicating better outcomes with the new treatment approach.

While two short consolidation cycles were easier to administer and had lower treatment-related mortality, they did not significantly improve event-free survival compared to the standard BFM-type consolidation, and the use of G-CSF shortened neutropenia but did not reduce severe infection rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Less toxicity by optimizing chemotherapy, but not by addition of granulocyte colony-stimulating factor in children and adolescents with acute myeloid leukemia: results of AML-BFM 98. Creutzig, U., Zimmermann, M., Lehrnbecher, T., et al.[2019]

In a study involving 271 children with acute myeloid leukemia (AML), 80% achieved complete remission, but there were significant early deaths (7%) due to hemorrhage and leukostasis, highlighting the need for improved initial treatment strategies.

Both studies (BFM-78 and BFM-83) showed similar long-term outcomes, with event-free survival rates around 37-40%, but initial hyperleukocytosis was identified as a high-risk factor for complications and relapses, indicating that targeted interventions for these patients are necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current results of cooperative AML therapy studies in children: BFM-78 and 83]. Creutzig, U., Ritter, J., Budde, M., et al.[2013]

In a phase II trial involving 26 patients with relapsed/refractory AML treated with sargramostim (GM-CSF) and bexarotene, 31% showed hematologic improvement in neutrophils, although no complete or partial remissions were achieved.

Another trial with 10 patients using GM-CSF and entinostat resulted in 10% achieving partial remission and 20% showing hematologic improvement, indicating that while the treatments were well tolerated, their clinical efficacy was modest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differentiation therapy in poor risk myeloid malignancies: Results of companion phase II studies. Norsworthy, KJ., Cho, E., Arora, J., et al.[2022]

Normal human bone marrow fibroblast-conditioned medium (BMF-CM) can suppress the growth of certain leukemic cells, specifically K562 cells and undifferentiated acute myelocytic leukemia cells, indicating a potential therapeutic role in these types of leukemia.

Conversely, BMF-CM appears to stimulate the proliferation of differentiated leukemic cells and those from patients with chronic myelogenous leukemia, suggesting that its effects vary based on the differentiation stage of the leukemia cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone marrow fibroblasts-conditioned medium regulates the proliferation of leukemic cells. Kubota, T., Nagao, T., Arimori, S.[2007]

This study found that both high-molecular-weight (HMW) and low-molecular-weight (LMW) B cell growth factors (BCGF) bind to B cell precursor cells in acute lymphoblastic leukemia (ALL), with LMW-BCGF showing a stronger stimulatory effect in 75% of cases compared to 33% for HMW-BCGF.

The research indicates that patients with specific chromosomal abnormalities, such as those involving 12p11-13 or the Philadelphia chromosome, have a greater response to HMW-BCGF, suggesting that these genetic factors may influence the effectiveness of BCGF in promoting B cell proliferation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B-cell growth factor receptor expression and B-cell growth factor response of leukemic B cell precursors and B lineage lymphoid progenitor cells. Uckun, FM., Fauci, AS., Heerema, NA., et al.[2021]

Citations

1. investors.biomeafusion.com investors.biomeafusion.com/news-releases/news-release-details/biomea-fusion-presents-updated-preliminary-clinical-data

Biomea Fusion Presents Updated Preliminary Clinical Data for ... New clinical results show sustained CRi, deep bone marrow responses, and encouraging survival in FLT3-mutant AML patients, including those previously treated ...

2. library.ehaweb.org library.ehaweb.org/eha/2025/eha2025-congress/4160595/farhad.ravandi-kashani.covalent.flt3.inhibitor.bmf-500.in.relapsed.or.html

COVALENT FLT3 INHIBITOR BMF-500 IN RELAPSED OR ... BMF-500 lacks cKIT inhibition, exhibits cytotoxicity even after washout, and elicits improved survival in FLT3m AML xenografts. Aims: Here we ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05918692

A Phase 1 Study of BMF-500 in Adults With Acute Leukemia A Phase 1 first-in-human dose-escalation and dose-expansion study of BMF-500, an oral covalent FLT3 inhibitor, in adult patients with acute myeloid leukemia ...

4. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1546/503468/Covalent-103-A-Phase-1-Open-Label-Dose-Escalation

Covalent-103: A Phase 1, Open-Label, Dose-Escalation, and ... BMF-500 has demonstrated high affinity for FLT3, lack of cKIT inhibition, and sustained cell-killing capacity despite drug washout (Law et al., ...

5. nasdaq.com nasdaq.com/articles/biomea-fusion-reports-preliminary-phase-i-clinical-data-bmf-500-relapsed-or-refractory

Biomea Fusion Reports Preliminary Phase I Clinical Data ... The median overall survival for patients was reported to be better than historical averages. BMF-500 was generally well-tolerated with no severe ...

6. investors.biomeafusion.com investors.biomeafusion.com/news-releases/news-release-details/biomea-fusion-announces-preliminary-data-ongoing-covalent-103

Biomea Fusion Announces Preliminary Data from Ongoing ... ... leukemia BMF-500 showed a favorable safety and tolerability profile, with no dose-limiting toxicities observed across all dose levels ...