BL-M11D1 for Acute Myeloid Leukemia

Recruiting at 8 trial locations

Overseen By Whitney Eakins

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: SystImmune Inc.

Must not be taking: Immunosuppressants, Antihypertensives, Anticancer, others

Disqualifiers: Heart disease, Autoimmune diseases, Infections, others

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

Compensation: Varies

Number of Visits: 2

120 Participants Needed

Trial Summary

What is the purpose of this trial?

The objective of this study to evaluate the safety, tolerability, pharmacokinetic profile, and preliminary efficacy of BL-M11D1 in patients with relapsed/refractory acute myeloid leukemia.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain anticancer therapies and other treatments like chemotherapy, biological therapy, and immunotherapy at least 2 weeks before starting the study. If you're on mitomycin or nitrosoureas, you need to stop them 6 weeks before. It's best to discuss your specific medications with the trial team to see if they need to be paused.

What data supports the effectiveness of the drug BL-M11D1 for treating Acute Myeloid Leukemia?

Research suggests that targeting the protein MCL-1, which is involved in preventing cell death, can be effective in treating Acute Myeloid Leukemia (AML). Inhibiting MCL-1 has been shown to work well with other chemotherapy drugs to kill cancer cells in AML, indicating that treatments targeting MCL-1 could be promising for AML patients. ^{1 2 3 4 5}

What safety data exists for the treatment BL-M11D1 in humans?

There is no specific safety data available for BL-M11D1, but selinexor, a similar treatment, has been studied in patients with acute myeloid leukemia. In these studies, common side effects included fatigue, gastrointestinal issues, and low sodium levels, but they were generally manageable with care. ^{5 6 7 8 9}

What makes the drug BL-M11D1 unique for treating acute myeloid leukemia?

BL-M11D1 may target the MCL-1 protein, which is crucial for the survival of acute myeloid leukemia cells. This approach is different from traditional treatments as it focuses on inhibiting a specific protein that helps cancer cells avoid death, potentially improving treatment outcomes. ^{1 3 5 10 11}

Eligibility Criteria

This trial is for people with Acute Myeloid Leukemia (AML) who have tried other treatments that didn't work. Participants should be in a condition where they can handle the study procedures and follow-up visits.

Inclusion Criteria

My AML has returned or didn't respond to first treatment and tests positive for CD33.

Has a life expectancy of ≥3 months

Signed the informed consent

Exclusion Criteria

I have recently used cancer treatments.

Recent use of investigational drugs

I have been diagnosed with APL or CML in blast crisis.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive BL-M11D1 in a dose-escalation format to determine the maximum tolerated dose

28 days per cycle

1 visit (in-person) per cycle

Dose Finding

Participants receive BL-M11D1 to determine the minimum safe and effective dose

28 days per cycle

1 visit (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• BL-M11D1

Trial Overview The trial is testing BL-M11D1, a new potential treatment for AML. It's an open-label study, meaning both doctors and patients know what's being given. They're looking at how safe it is, how the body processes it, and if it helps against AML.

Participant Groups

Group I: Experimental: BL-M11D1 administered Day 1 per cycle Experimental Treatment 1 Intervention

BL-M11D1 will be administered on Day 1 by intravenous infusion every 28 days.

Who Is Running the Clinical Trial?

SystImmune Inc.

Lead Sponsor

Trials

23

Recruited

1,800+

Findings from Research

In a study of 46 newly diagnosed acute myeloid leukemia (AML) patients, GLI-1 was found to be overexpressed in bone marrow samples, particularly in patients with poor risk categories, indicating its potential role as a prognostic marker.

Higher levels of GLI-1 mRNA were associated with a lack of complete remission after chemotherapy, suggesting that GLI-1 overexpression could be a novel therapeutic target for improving outcomes in AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High GLI-1 Expression is a Reliable Indicator of Bad Prognosis in Newly Diagnosed Acute Leukemia Patients. El Zaiat, RS., Nabil, R., Khalifa, KA., et al.[2023]

In a phase 1 study involving 23 patients with relapsed/refractory acute myeloid leukemia (AML), the combination of selinexor with mitoxantrone, etoposide, and cytarabine showed an overall response rate of 43%, with 26% of patients achieving complete remission.

The maximum tolerated dose of selinexor was determined to be 30 mg/m2 due to dose-limiting side effects, including hyponatremia, indicating that while the treatment is promising, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of selinexor in combination with salvage chemotherapy in Adults with relapsed or refractory Acute myeloid leukemia. Bhatnagar, B., Zhao, Q., Mims, AS., et al.[2023]

Selinexor, a selective inhibitor of nuclear export, was found to be safe and well-tolerated in a phase 1 study involving 95 patients with relapsed or refractory acute myeloid leukemia (AML), with manageable side effects primarily being mild gastrointestinal and constitutional toxicities.

The study showed that 14% of evaluable patients achieved an objective response, leading to significantly improved progression-free survival (5.1 months vs. 1.3 months) and overall survival (9.7 months vs. 2.7 months) compared to nonresponders, indicating its potential efficacy as a treatment for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 clinical trial of single-agent selinexor in acute myeloid leukemia. Garzon, R., Savona, M., Baz, R., et al.[2021]

Selinexor is a novel oral medication being investigated for treating acute myeloid leukemia (AML), which is particularly challenging to treat in older adults.

This meta-analysis aims to assess the efficacy and safety of selinexor in AML treatment by reviewing randomized controlled trials, providing valuable evidence to guide clinical decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of selinexor in the treatment of AML: A protocol for systematic review and meta-analysis. Yu, L., Yin, X., Si, Y., et al.[2023]

References

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

Mcl1 haploinsufficiency protects mice from Myc-induced acute myeloid leukemia. [2023]

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

Should patients with acute myeloid leukemia and measurable residual disease be transplanted in first complete remission? [2018]

3. China pubmed.ncbi.nlm.nih.gov

[Expression of MCL-1 in Primary Acute Myeloid Leukemia Cells and Its Clinical Significance]. [2018]

4. India pubmed.ncbi.nlm.nih.gov

High GLI-1 Expression is a Reliable Indicator of Bad Prognosis in Newly Diagnosed Acute Leukemia Patients. [2023]

5. Slovakia pubmed.ncbi.nlm.nih.gov

Synergistic activity and mechanism of cytarabine and MCL-1 inhibitor AZD5991 against acute myeloid leukemia. [2023]

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

Phase 1 study of selinexor in combination with salvage chemotherapy in Adults with relapsed or refractory Acute myeloid leukemia. [2023]

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

A phase 1 clinical trial of single-agent selinexor in acute myeloid leukemia. [2021]

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

Efficacy and safety of thalidomide in patients with acute myeloid leukemia. [2021]

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

Efficacy and safety of selinexor in the treatment of AML: A protocol for systematic review and meta-analysis. [2023]

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

Anti-apoptotic Mcl-1 is essential for the development and sustained growth of acute myeloid leukemia. [2022]

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

BCL2L10 positive cells in bone marrow are an independent prognostic factor of azacitidine outcome in myelodysplastic syndrome and acute myeloid leukemia. [2018]