BXCL701 for AML or MDS

Overseen By Eric S Winter, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Eric Stephen Winer, MD

Must not be taking: Gliptins, TKIs, others

Disqualifiers: Acute promyelocytic leukemia, active CNS involvement, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 months

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this research study is to find the safest and most effective dose of the study drug, BXCL701, for the treatment of Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS). The names of the study drugs involved in this study are/is: * BXCL701

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but it strongly encourages changing drugs that strongly affect CYP3A4 enzymes if possible. You cannot take certain diabetes medications (gliptins) during the trial.

How is the drug BXCL701 different from other treatments for AML or MDS?

BXCL701 is unique because it targets the multidrug resistance gene (MDR1), which is often overexpressed in AML and MDS, making these cancers resistant to standard treatments. By inhibiting MDR1, BXCL701 may help overcome this resistance and improve treatment effectiveness. ^{1 2 3 4 5}

Who Is on the Research Team?

Eric S Winter, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS), who have specific blood and organ function levels, can join. Those with HIV or hepatitis must be on effective treatment with an undetectable viral load. Participants should not have other active cancers, CNS leukemia involvement, or recent treatments that could interfere.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

My organs are functioning well, and I understand the risks and consent.

My condition is either relapsed or refractory AML, or I have a type of MDS with excess blasts-2.

Exclusion Criteria

I have been diagnosed with Acute Promyelocytic Leukemia.

My acute myeloid leukemia has spread to my brain or spinal cord.

I am eligible for this trial regardless of my gender or ethnicity.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BXCL701 in a dose escalation approach, taking the drug 2x daily during each 28-day cycle for up to 12 cycles

12 months

Disease assessment at baseline, cycle 1, 3, 8, 15, 22, and day 1 of every cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• BXCL701

Trial Overview The trial is testing the safety and effectiveness of a drug called BXCL701 for AML/MDS patients. It aims to determine the best dose by monitoring participants' reactions over time.

How Is the Trial Designed?

Group I: Dose Escalation BXCL701 Experimental Treatment 1 Intervention

Dose escalation will occur using a 3+3 dose escalation approach, evaluating 4 different dose levels of BXCL701. During each 28 day study cycle participants will take BXCL701 2x daily for up to 12 cycles.

BXCL701 is already approved in United States for the following indications:

Approved in United States as BXCL701 for:

• Acute Myeloid Leukemia (AML)
• Myelodysplastic Syndrome (MDS)
• Small Cell Neuroendocrine Prostate Cancer (SCNC)
• Pancreatic Cancer
• Stage IIb to IV Melanoma
• Soft Tissue Sarcoma

Who Is Running the Clinical Trial?

Eric Stephen Winer, MD

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

The combination of the MDR1 blocker SDZ PSC-833 with mitoxantrone and etoposide showed tolerable antileukemic activity in patients with relapsed acute myelogenous leukemia, although it required a significant dose reduction of these drugs due to toxicity.

Despite the treatment leading to some clearance of leukemia cells in the blood and bone marrow, no patients achieved complete remission, highlighting the need for further research to improve outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia. Kornblau, SM., Estey, E., Madden, T., et al.[2017]

The study evaluated various methods for detecting the MDR1 gene in acute myelogenous leukemia (AML), finding that RT-PCR was more sensitive than Northern blot analysis, but also more prone to contamination from normal cells.

A modified method for estimating total MDR1 mRNA in leukemic cell populations was developed, which could be useful for large clinical trials and revealed that certain leukemia subtypes, like FAB M3, were mostly MDR1 negative.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Methods for detection of MDR1 mRNA expression on acute myelogenous leukemia cells. Sato, H., Oonishi, T., Wada, C.[2018]

In a study of 74 patients with acute myelogenous leukaemia (AML), high levels of MDR1 gene expression were associated with difficulty in achieving remission and shorter remission durations after treatment.

The findings suggest that elevated MDR1 expression may contribute to the ineffectiveness of anthracycline-based treatments in some AML patients, indicating a potential mechanism for treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MDR1 transcript levels as an indication of resistant disease in acute myelogenous leukaemia. Sato, H., Preisler, H., Day, R., et al.[2019]

Younger acute myeloid leukemia (AML) patients with the multidrug resistance gene-1 (MDR1) expression have a poor prognosis, indicating that MDR1 is a significant factor in predicting treatment response.

Elderly AML patients who are MDR1-negative can achieve high complete response rates (around 75%) with induction chemotherapy, suggesting they may have favorable outcomes despite their age, while MDR1-positive elderly patients are less likely to respond well to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunophenotyping and cytogenetics in older adults with acute myeloid leukemia: significance of expression of the multidrug resistance gene-1 (MDR1). Willman, CL.[2013]

In a study of 73 leukemia patients, 31 showed positive expression of the multidrug resistance gene MDR1, indicating a significant correlation between high MDR1 levels and chemotherapy resistance, particularly in relapsed acute leukemia and chronic myeloid leukemia (CML) in blast crisis.

Patients with MDR1+ expression had a much higher refractory rate to chemotherapy (75%) compared to those who were MDR1- (15%), suggesting that measuring MDR1 expression can help tailor more effective treatment plans for individual leukemia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Analysis of the multidrug resistance MDR1 gene expression in clinical leukemia with RT-PCR]. Zhang, H., Shi, G., Wang, J.[2018]

Citations

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

Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia. [2017]

2. Japan pubmed.ncbi.nlm.nih.gov

Methods for detection of MDR1 mRNA expression on acute myelogenous leukemia cells. [2018]

3. England pubmed.ncbi.nlm.nih.gov

MDR1 transcript levels as an indication of resistant disease in acute myelogenous leukaemia. [2019]

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

Immunophenotyping and cytogenetics in older adults with acute myeloid leukemia: significance of expression of the multidrug resistance gene-1 (MDR1). [2013]

5. China pubmed.ncbi.nlm.nih.gov

[Analysis of the multidrug resistance MDR1 gene expression in clinical leukemia with RT-PCR]. [2018]