A Multicenter, Open-Label Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile, and Preliminary Efficacy of BL-M11D1 in Patients With Relapsed/Refractory Acute Myeloid Leukemia.
Overview
- Phase
- Phase 1
- Intervention
- BL-M11D1
- Conditions
- Relapsed/Refractory Acute Myeloid Leukemia
- Sponsor
- SystImmune Inc.
- Enrollment
- 120
- Locations
- 14
- Primary Endpoint
- Participants with dose-limiting toxicities
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
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 A will be dosed on Days 1, 8,15 of a continuous 28-day treatment cycle. The cohort has different dose groups. Cohort B will be dosed on Days 1, 4, 7 or 8 of a continuous 28-day treatment cycle. The cohorts have different dose groups.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed the informed consent
- •Age ≥18 years
- •Has a life expectancy of ≥3 months
- •Relapsed and/or refractory CD33-positive AML as determined by local pathology review 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
- •Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2
- •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
- •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)
- •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
- •Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and must be nonlactating
Exclusion Criteria
- •Subjects with acute promyelocytic leukemia (APL) or chronic myelogenous leukemia in blast crisis (CML)
- •Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other anticancer therapy within 2 weeks) 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
- •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 within 6 months before screening
- •Subjects with prolonged QT interval (QTcF \>470 msec), complete left bundle branch block, Grade 3 atrioventricular block or a history of additional risk factors for Torsades de Pointes (TdP; eg, heart failure as defined in Exclusion Criterion 3, chronic or recurrent hypokalemia that requires medical intervention, congenital long QT syndrome, family history of long QT syndrome) or any current concomitant medication known to prolong the QT/QTc interval or cause TdP
- •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)
- •Subjects with other prior or concurrent malignancies except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after adequate resection, or other malignancy treated with curative intent with as disease-free interval of at least 1 year
- •Subjects with poorly controlled hypertension or uncontrolled hypertension by two or more antihypertensive drugs (systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg)
- •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
- •Subjects currently receiving immunosuppressive therapy should be excluded from this study.
- •Clinical evidence of disseminated intravascular coagulation (DIC). Smoldering low grade DIC is allowed after discussion with the sponsor
Arms & Interventions
Experimental: Cohort A BL-M11D1 administered Days 1, 8 and 15 in 28-day cycle
Cohort A: BL-M11D1 will be administered on Days 1, 8 and 15 by intravenous infusion every 28 days.
Intervention: BL-M11D1
Experimental: Cohort B BL-M11D1 administered Days 1, 4 7 or 8 in 28-day cycle
Cohort B: BL-M11D1 will be administered on Days 1,4, 7 or 8 by intravenous infusion every 28 days.
Intervention: BL-M11D1
Outcomes
Primary Outcomes
Participants with dose-limiting toxicities
Time Frame: 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)
Time Frame: 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
Time Frame: 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 Outcomes
- Cmax of BL-M11D1(1 Year)
- Tmax of BL-M11D1(1 Year)
- Tmax of free payload ED-04(1 Year)
- Cmax of free payload ED-04(1 Year)
- AUC(0-8) of BL-M11D1(1 Year)
- AUC(0-8) of free payload ED-04(1 Year)
- AUC(last) of BL-BM11D1(1 Year)
- AUC(last) of free payload ED-04(1 Year)
- Tmax of anti-CD33 antibody(1 Year)
- AUC (0-8) of anti-CD33 antibodies(1 Year)
- AUC (last) anti-CD33 antibodies(1 Year)
- Overall Response Rate (ORR)(1 Year)
- Duration of response (DOR)(1 Year)
- Complete Remission (CR)(1 Year)
- CR with partial hematologic recovery (CRh)(1 Year)
- CR with incomplete hematologic recovery (CRi)(1 Year)
- CR/CRi, CRs with or without measurable residual disease (MRD)(1 Year)
- morphologic leukemia-free state (MLFS)(1 Year)
- partial remission (PR)(1 Year)