Hematologic Malignancies, Multiple Myeloma
Conditions
Brief summary
This study is an open, multicenter, non-randomized phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics characteristics and preliminary efficacy of BL-M24D1 in patients with relapsed or refractory multiple myeloma and other hematologic malignancies.
Detailed description
The study is divided into two phases: a dose escalation phase (Phase Ia) and an expansion cohort phase (Phase Ib).
Interventions
DRUGBL-M24D1
Administration by intravenous infusion for a cycle of 2 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 No maximum
Healthy volunteers
No
Inclusion criteria
1. Voluntarily sign the informed consent form and comply with the protocol requirements; 2. Gender is not restricted; 3. Age: ≥18 years and ≤75 years (Phase Ia); ≥18 years (Phase Ib); 4. Expected survival time ≥3 months; 5. Histologically and/or cytologically confirmed multiple myeloma or other hematologic malignancies that have failed standard treatment or for which no standard treatment currently exists; 6. Must have measurable indicators as defined by the protocol; 7. Physical condition score ECOG 0 or 1; 8. Toxicity from previous antitumor treatments has recovered to ≤ Grade 1 as defined by NCI-CTCAE v5.0; 9. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%; 10. Organ function levels must meet the requirements; 11. Coagulation function: International Normalized Ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5 × ULN; 12. For premenopausal women with childbearing potential, a pregnancy test must be conducted within 7 days before starting treatment, the serum pregnancy test must be negative, and they must not be breastfeeding; all enrolled patients (regardless of gender) should adopt adequate barrier contraception throughout the treatment cycle and for 6 months after the end of treatment.
Exclusion criteria
1. Subjects with central nervous system involvement, etc.; 2. Use of chemotherapy, biologics, immunotherapy, etc., within 4 weeks prior to the first dose or within 5 half-lives; 3. History of severe heart disease; 4. QT interval prolongation, complete left bundle branch block, third-degree atrioventricular block; 5. Active autoimmune diseases and inflammatory diseases; 6. Diagnosis of other malignancies within 5 years prior to the first dose; 7. Hypertension poorly controlled by two antihypertensive medications; 8. Patients with poorly controlled blood glucose; 9. Unstable thrombotic events requiring therapeutic intervention within 6 months prior to the first dose; 10. Lung diseases defined as ≥ Grade 3 according to CTCAE v5.0; history of interstitial lung disease requiring hormone treatment, etc.; 11. Patients with peripheral neuropathy ≥ Grade 3 or persistent ≥ Grade 2 peripheral neuropathy with pain; 12. Patients with a history of allergy to recombinant humanized antibodies or human-mouse chimeric antibodies, or allergy to any excipient component of BL-M24D1; 13. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT); 14. Human immunodeficiency virus antibody positivity, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection; 15. Active infection requiring systemic treatment within 4 weeks prior to the first study drug administration, etc.; 16. Pleural, abdominal, pelvic, or pericardial effusion requiring drainage and/or accompanied by symptoms within 4 weeks prior to the first study drug administration; 17. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks prior to the first study drug administration; 18. Participation in another clinical trial within 4 weeks prior to the first dose; 19. Pregnant or breastfeeding women; 20. Patients who received live vaccines within 30 days prior to the first dose; 21. Other conditions deemed by the investigator as unsuitable for participation in this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ia: Dose limiting toxicity (DLT) | Up to 28 days after the first dose | DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration. |
| Phase Ia: Maximum tolerated dose (MTD) | Up to 28 days after the first dose | MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle. |
| 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-M24D1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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-M24D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-M24D1. |
| Cmax | Up to approximately 24 months | Maximum serum concentration (Cmax) of BL-M24D1 will be investigated. |
| Tmax | Up to approximately 24 months | Time to maximum serum concentration (Tmax) of BL-M24D1 will be investigated. |
| T1/2 | Up to approximately 24 months | Half-life (T1/2) of BL-M24D1 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-M24D1 per unit of time will be investigated. |
| Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration of BL-M24D1 prior to the next dose will be administered. |
| ADA (anti-drug antibody) | Up to approximately 24 months | Frequency of anti-BL-M24D1 antibody (ADA) will be investigated. |
| Phase Ib: 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 Ib: 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. |
Countries
China
Contacts
CONTACTSa Xiao, PHD
Outcome results
None listed