Myelodysplastic Syndromes
Conditions
Brief summary
This study is an open-label, multicenter, non-randomized Phase Ib/II clinical study to evaluate the safety, tolerability, and pharmacokinetic characteristics of BL-M11D1 for injection in patients with relapsed/refractory myelodysplastic syndromes.
Detailed description
The study consists of two phases: a dose-exploration phase (Phase Ib) and a dose-expansion phase (Phase II).
Interventions
DRUGBL-M11D1
Administration by intravenous infusion for a cycle of 4 weeks.
Sponsors
Sichuan Baili Pharmaceutical Co., Ltd.
Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntarily sign the informed consent form and comply with the protocol requirements; 2. No gender restrictions; 3. Age: ≥18 years and ≤75 years; 4. Expected survival time ≥3 months; 5. Relapsed/refractory CD33+ MDS; 6. Morphological assessment showing blasts in bone marrow ≥5% and \<20%; 7. Eastern Cooperative Oncology Group (ECOG) performance status ≤2; 8. Toxicities from prior anti-tumor therapy must have recovered to ≤ Grade 1 as defined by NCI-CTCAE v6.0; 9. Meet the required organ function levels; 10. For premenopausal women of childbearing potential, a pregnancy test (serum/urine) must be negative within 7 days before starting treatment, and they must not be breastfeeding; all enrolled trial participants (regardless of gender) must practice adequate barrier contraception throughout the entire treatment period and for 6 months after treatment completion.
Exclusion criteria
1. Use of chemotherapy, biotherapy, immunotherapy, etc., within 4 weeks or 5 half-lives prior to the first dose; 2. Presence of uncorrected folate deficiency or vitamin B12 deficiency, etc.; 3. History of severe cardiovascular or cerebrovascular disease; 4. Thromboembolic events requiring therapeutic intervention within 6 months prior to screening; 5. Active autoimmune diseases and inflammatory diseases; 6. History of extensive bowel resection or presence of Crohn's disease, ulcerative colitis, chronic diarrhea, or intestinal obstruction; 7. Diagnosis of another malignancy within 5 years prior to the first dose; 8. Poorly controlled hypertension; 9. Poorly controlled hyperglycemia or diabetes mellitus; 10. Pulmonary diseases classified as Grade ≥3 according to CTCAE v6.0, etc.; 11. Trial participants with central nervous system involvement; 12. Trial participants with extramedullary involvement; 13. Trial participants with a history of allergy to recombinant humanized antibodies or chimeric human-mouse antibodies, or hypersensitivity to any excipient component of BL-M11D1; 14. Prior organ transplantation or hematopoietic stem cell transplantation; 15. Positive for human immunodeficiency virus antibody, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection; 16. Active fungal, bacterial, or viral infections; 17. History of severe neurological or psychiatric disorders; 18. Trial participants with clinically significant bleeding or obvious bleeding tendency within 4 weeks prior to signing informed consent; 19. Presence of clinically symptomatic pleural, peritoneal, or pericardial effusion requiring repeated drainage; 20. Participation in another clinical trial within 4 weeks or 5 half-lives prior to the first dose; 21. Pregnant or breastfeeding women; 22. Other conditions deemed by the investigator to make the participant unsuitable for participation in this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ib: Recommended Phase II Dose (RP2D) | Up to approximately 24 months | The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of BL-M11D1. |
| Phase Ib: Treatment-Emergent Adverse Event (TEAE) | Up to approximately 24 months | TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-M11D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-M11D1. |
| Phase II: Objective Response Rate (ORR) | Up to approximately 24 months | ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1. |
| Phase II: Complete Response (CR) | Up to approximately 24 months | Complete Response (CR) is defined as the disappearance of all target lesions, with any pathological lymph nodes (whether target or non-target) having a short axis diameter reduced to \<10 mm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | Up to approximately 24 months | Maximum serum concentration (Cmax) of BL-M11D1 will be investigated. |
| Tmax | Up to approximately 24 months | Time to maximum serum concentration (Tmax) of BL-M11D1 will be investigated. |
| T1/2 | Up to approximately 24 months | Half-life (T1/2) of BL-M11D1 will be investigated. |
| AUC0-t | Up to approximately 24 months | AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration. |
| CL (Clearance) | Up to approximately 24 months | CL in the serum of BL-M11D1 per unit of time will be investigated. |
| Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration of BL-M11D1 prior to the next dose will be administered. |
| ADA (anti-drug antibody) | Up to approximately 24 months | Frequency of anti-BL-M11D1 antibody (ADA) will be investigated. |
| Phase II: Duration of Response (DOR) | Up to approximately 24 months | The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first. |
| Phase II: Hematologic Improvement (HI) | Up to approximately 24 months | HI is defined as achieving a predefined threshold of improvement in the erythroid, platelet, or neutrophil lineages according to the IWG 2006 and IWG 2023 criteria, with a duration of no less than 8 weeks. |
| Phase II: AML Transformation Rate | Up to approximately 24 months | The AML transformation rate is defined as the first confirmed event of transformation to acute myeloid leukemia according to WHO criteria (bone marrow blasts ≥20% or presence of extramedullary infiltration). |
Countries
China
Contacts
CONTACTSa Xiao, PHD
Outcome results
None listed