Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile, Efficacy of BL-M11D1 in Patients With Relapsed/Refractory Acute Myeloid Leukemia

Phase 1

Recruiting

• Conditions: Relapsed/Refractory Acute Myeloid Leukemia
• Interventions: Drug: BL-M11D1

• Registration Number: NCT06714591
• Lead Sponsor: SystImmune Inc.

Brief Summary

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.

Detailed Description

BL-M11D1-HM-101 is a multi-center, Phase 1 study to evaluate the safety, tolerability, pharmacokinetic profile, and preliminary efficacy of BL-M11D1 in patients with relapsed/refractory acute myeloid leukemia.

This study will be conducted in two parts (dose escalation, and dose finding). Cohort will be dosed on Day 1 of a continuous 28-day treatment cycle. The cohort has different dose groups.

Study Timeline

• Study First Submitted: 2024-11-27
• Study First Submitted QC: 2024-11-27
• Study First Posted: 2024-12-03
• Study Start: 2024-12-19
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-24
• Last Update Posted: 2025-04-29
• Primary Completion: 2026-12-31
• Study Completion: 2027-03-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Signed the informed consent
2. Age ≥18 years
3. Has a life expectancy of ≥3 months
4. Relapsed and/or refractory CD33-positive AML as determined by pathology review at the treating institution that has failed initial standard of care therapy. Diagnosis of primary AML or AML secondary to myelodysplastic syndromes. Relapsed or refractory status. CD33-positive as confirmed by local flow cytometry or cytology.
5. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2
6. Toxicity of previous anticancer therapy has returned to Grade ≤1 as defined by NCI CTCAE V5.0, except for alopecia and endocrinopathies controlled by replacement therapy that must be Grade ≤2
7. Has adequate liver and renal function before registration, defined as: a. Hepatic function: Total bilirubin (TBIL) ≤1.5×ULN (≤3×ULN for subjects with Gilbert's syndrome), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN b. Renal function: Creatinine clearance ≥50 mL/min (Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration [CKD-Epi], or Modification of Diet in Renal Disease Study [MDRD] equations)
8. Sexually active fertile subjects and their partners must agree to use highly effective methods of contraception during the course of the study and for 7 months after the last dose of study treatment. An additional contraceptive method, such as a barrier method (eg, condom), is recommended
9. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and must be nonlactating.

Exclusion Criteria

1. Subjects with acute promyelocytic leukemia (APL) or chronic myelogenous leukemia in blast crisis (CML)
2. Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other anticancer therapy within 2 weeks or 5 half-lives (3 half-lives for antibodies) (whichever is longer) prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration, or palliative radiotherapy within 2 weeks prior to the first administration
3. Subjects with history of severe heart disease, such as: symptomatic congestive heart failure (CHF) ≥ Grade 2 (CTCAE 5.0), New York Heart Association (NYHA) ≥ Grade 2 heart failure, history of transmural myocardial infarction, unstable cardiac arrhythmias or angina pectoris, etc.
4. Subjects with prolonged QT interval (QTcF >470 msec), complete left bundle branch block, Grade 3 atrioventricular block
5. Active autoimmune diseases and inflammatory diseases, such as: systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease and Hashimoto's thyroiditis, etc., except for Type I diabetes, hypothyroidism that can be controlled only by standard of care treatment, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis)
6. Subjects with other prior or concurrent malignant tumors were diagnosed within 5 years prior to the first administration with the following exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after radical resection, or other malignancy in which treatment does not interfere with the safety or efficacy assessment of the investigational product
7. Subjects with resistant and refractory hypertension or uncontrolled hypertension despite ≥3 different types of antihypertensive drugs (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg)
8. Subjects with active acute or chronic graft vs. host disease (aGVHD or cGVHD) should be excluded from this study. Subjects with GVHD who are receiving treatment with systemic glucocorticoids >10 mg/day equivalent of prednisone should also be excluded from the study; however, treatment with low-dose glucocorticoids (≤10 mg/day equivalent of prednisone) is permitted
9. Subjects currently receiving immunosuppressive therapy should be excluded from this study.
10. Clinical evidence of disseminated intravascular coagulation (DIC). Smoldering low grade DIC is allowed after discussion with the sponsor
11. Subjects with stroke (including transient ischemic attack [TIA]), myocardial infarction, or other ischemic event or thromboembolic event (eg, deep vein thrombosis [DVT] or pulmonary embolism [PE]) within 6 months before randomization except for those with a diagnosis of DVT who are stable and receiving treatment with adequate anticoagulant therapy for at least 3 weeks before randomization. Infusion set-related thrombosis is excluded
12. Subjects with active central nervous system (CNS) AML will be excluded. A lumbar puncture does not need to be performed unless there is clinical suspicion of CNS involvement per investigator judgment. Concurrent therapy for CNS prophylaxis or continuation of therapy for controlled CNS AML is allowed with the approval of the sponsor
13. Subjects with pre-existing ≥Grade 2 peripheral neuropathy
14. Subjects with Grade ≥3 lung disease defined by CTCAE v5.0
15. Subjects who have a history of noninfectious interstitial lung disease (ILD)/ pneumonitis that required treatment with steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
16. Subjects who have a history of allergies to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of BL-M11D1
17. Known human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number> the lower limit of detection) or active hepatitis C virus infection (HCV antibody positive and HCV-RNA > the lower limit of detection), active cytomegalovirus (CMV) infection
18. Subjects with active, uncontrolled infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc., that require use of intravenous antibiotics, antiviral drugs, or antifungal drugs within 2 weeks prior to start of treatment
19. Received an investigational drug within 4 weeks, or two half-lives (whichever is longer) prior to first dose of study treatment
20. Subjects who are pregnant or breastfeeding
21. Other conditions that the investigator or sponsor believes are not suitable for participating in this clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Experimental: BL-M11D1 administered Day 1 per cycle	BL-M11D1	BL-M11D1 will be administered on Day 1 by intravenous infusion every 28 days.

Primary Outcome Measures

Name	Time	Method
Participants with dose-limiting toxicities	1 Year	DLTs are defined as any of the following events that are not clearly due to the underlying disease, disease progression, or extraneous causes: * Any treatment-emergent adverse event (TEAE) of ≥ Grade 3 except those due to disease progression or extraneous cause; * Any TEAE that leads to dose reduction or withdrawal Nonhematologic toxicities; * Death; * Hy's law cases; * Grade ≥3 nonhematologic toxicities (with exceptions) Hematologic toxicity; * Grade 4 thrombocytopenia or neutropenia lasting \>42 days in the absence of persistent leukemia; * Grade ≥3 platelet count decreased with clinically significant hemorrhage
Participants with Serious Adverse Events (SAEs) and treatment-emergent adverse events (TEAEs)	1 Year	Measuring the number of patients with serious adverse events (SAEs) and treatment-emergent adverse events (TEAEs)
To determine the minimum safe and effective dose (MSED), maximum tolerated dose (MTD) if reached, and maximum administered dose (MAD) of BL-M11D1 in AML	1 Year	Determine the highest BL-M11D1 dose level at which ≤33% subjects experience a DLT during the DLT evaluation period and highest BL-M11D1 dose administered in the event and MTD cannot be defined.

Secondary Outcome Measures

Name	Time	Method
Cmax of BL-M11D1	1 Year	Calculate maximum (peak) observed concentration of BL-M11D1
Tmax of BL-M11D1	1 Year	Calculate time of maximum observed concentration of BL-M1D1
Tmax of free payload ED-04	1 Year	Calculate time of maximum observed concentration of free payload ED-04
Cmax of free payload ED-04	1 Year	Calculate maximum (peak) observed concentration of free payload ED-04
AUC(0-8) of BL-M11D1	1 Year	Calculate area under the serum concentration-time curve of BL-M11D1 from time 0 to 8 hours
AUC(0-8) of free payload ED-04	1 Year	Calculate area under the serum concentration-time curve of free payload ED-04 from time 0 to 8 hours
AUC(last) of BL-BM11D1	1 Year	Calculate area under the serum concentration-time curve up of BL-M11D1 to the last quantifiable time
AUC(last) of free payload ED-04	1 Year	Calculate area under the serum concentration-time curve up of free payload ED-04 to the last quantifiable time
Tmax of anti-CD33 antibody	1 Year	Calculate time of maximum observed concentration of anti-CD33 antibody
AUC (0-8) of anti-CD33 antibodies	1 Year	Calculate area under the serum concentration-time curve of anti-CD33 antibodies from time 0 to 8 hours
AUC (last) anti-CD33 antibodies	1 Year	Calculate area under the serum concentration-time curve up of anti-CD33 antibodies to the last quantifiable time
Overall Response Rate (ORR)	1 Year	To assess the clinical efficacy of BL-M11D1 as measured by ORR using RECIST criteria v 1.1
Duration of response (DOR)	1 Year	To access the clinical efficacy of BL-M11D1 as measured by DOR using RECIST criteria 1.1
Complete Remission (CR)	1 Year	To assess the anti-cancer activity of BL-M11D1 as measured by CR using the European LeukemiaNet (ELN) 2022 AML criteria.
CR with partial hematologic recovery (CRh)	1 Year	To assess the anti-cancer activity of BL-M11D1 as measured by CR using the European LeukemiaNet (ELN) 2022 AML criteria.
CR with incomplete hematologic recovery (CRi)	1 Year	To assess the anti-cancer activity of BL-M11D1 as measured by CR using the European LeukemiaNet (ELN) 2022 AML criteria.
CR/CRi, CRs with or without measurable residual disease (MRD)	1 Year	To assess the anti-cancer activity of BL-M11D1 as measured by CR using the European LeukemiaNet (ELN) 2022 AML criteria.
morphologic leukemia-free state (MLFS)	1 Year	To assess the anti-cancer activity of BL-M11D1 as measured by CR using the European LeukemiaNet (ELN) 2022 AML criteria.
partial remission (PR)	1 Year	To assess the anti-cancer activity of BL-M11D1 as measured by CR using the European LeukemiaNet (ELN) 2022 AML criteria.

Trial Locations

Locations (9)

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

START Midwest/The Cancer and Hematology Center; 🇺🇸 Grand Rapids, Michigan, United States

Oncology Hematology Care Clinical Trials, LLC; 🇺🇸 Cincinnati, Ohio, United States

WVCI Oncology Associates of Oregon; 🇺🇸 Eugene, Oregon, United States

SCRI -TriStar BMT; 🇺🇸 Nashville, Tennessee, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Texas Oncology, P.A.; 🇺🇸 San Antonio, Texas, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States

Oncology & Hematology Associates of Southwest Virginia, Inc.; 🇺🇸 Roanoke, Virginia, United States