Plasma cell myeloma
Conditions
Interventions
C group:QLS32015 for injection is combined with QL2109 injection (daratumumab) and pomalidomide
A group:Injectable QLS32015 combined with pomalidomide capsules
D group:Injectable QLS32015 combined with bortezomib and lenalidomide capsules for injection
B group:QLS32015 for injection in combination with QL2109 injection (daratumumab)
Sponsors
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Subjects voluntarily participate and sign written informed consent; 2. Age>=18 years old, gender is not limited; 3. Patients with multiple myeloma diagnosed according to the 2016 International Myeloma Working Group (IMWG) diagnostic criteria; 4. Relapse or progression or intolerance after receiving >=1 line of anti-myeloma therapy in the past. (See Appendix 2 for the definition of relapsed or refractory); 5. Measurable lesions in patients with multiple myeloma at screening, defined as meeting any of the following: (1) Serum M protein level >=1.0 g/dL (10 g/L); (2) Urine M protein level >=200 mg/24 h; (3) Serum immunoglobulin free light chain >=10 mg/dL (100 mg/L) and abnormal serum immunoglobulin ?/? free light chain ratio; 6. Hematology meets the following criteria: (1) Hemoglobin: >=8.0 g/dL (80 g/L, >=5 mmol/L) (red blood cells [RBCs] cannot be transfused within 7 days before laboratory examination; recombinant human erythropoietin is allowed); (2) Platelets (PLT): platelet count >=75×10^9 /L (no transfusion support or platelet-stimulating factor must have been received within 7 days before laboratory examination); (3) Absolute neutrophil count (ANC): >=1.0×10^9/L (previous use of growth factors is allowed, but no supportive treatment of growth factors within 7 days prior to laboratory examination); 7. Biochemical laboratory checks meet the following conditions: (1) Aspartate aminotransferase and alanine aminotransferase (ALT/AST): =40 mL/min/1.73m^2, calculated according to the Cockcroft-Gault formula; (3) Total bilirubin (TBIL): =3 months; 10. Patients of childbearing potential (male and female) must agree to use at least 2 reliable methods of contraception (hormonal or barrier method or abstinence) with their partner during the trial and for at least 100 days after the last dose; Female patients of childbearing age must have a negative blood pregnancy test within 10-14 days before the first dose; 11. Male subjects must agree not to donate sperm for reproductive purposes during the study and for 100 days after the last dose of the investigational drug; 12. Subjects must agree not to donate eggs (oocytes, oocytes) or freeze eggs for future use for assisted reproduction during the study and for at least 100 days after the last dose of investigational medicinal product. Because anti-cancer treatment may impair fertility, subjects should consider saving eggs before starting study treatment; 13. Willing and able to follow the contraindications and restrictions set forth in this program.
Exclusion criteria
Exclusion criteria: 1. Previous Grade 3 or higher cytokine release syndrome associated with any T cell redirecting therapy (e.g., CD-3 redirection technique or CAR-T cell therapy); 2. The patient has received the following prior anti-tumor therapy before the first dose of the investigational drug: (1) Previous GPRC5D targeted therapy; (2) Received genetically modified adoptive cell therapy (e.g., chimeric antigen receptor-modified T cells [CAR-T], natural killer [NK] cells) within 3 months; (3) Received targeted therapy, investigational drug therapy, or invasive investigational medical device within 21 days or at least 5 half-lives (whichever is longer, or 21 days washout if the half-life is not known); (4) Treatment of multiple myeloma with monoclonal antibodies or bispecific antibodies within 21 days or at least 5 half-lives (whichever is longer, or 21 days of eluting if the half-life is not known); (5) Received cytotoxic drug therapy within 21 days; (6) Received proteasome inhibitor therapy within 14 days; (7) Received immunomodulatory therapy within 7 days; (8) Received radiotherapy within 14 days (except low-dose radiotherapy [10~30Gy] as palliative care); 3. Previous intolerance to pomalidomide (applicable to the pomalidomide-containing treatment cohort); 4. Previous intolerance to bortezomib (for bortezomib-containing treatment cohort); 5. Previous intolerance to lenalidomide (for lenalidomide-containing treatment cohort); 6. Previous intolerance to daratumumab (applicable to daratumumab treatment cohort); 7. Vaccination with live attenuated vaccine within 4 weeks prior to the first dose of the investigational drug, or anticipation of need for vaccination with live attenuated vaccine during the study; 8. Except for alopecia (any grade) or peripheral neuropathy (grade =2 peripheral neuropathy or =grade 1 peripheral neuropathy with pain), the toxicity of previous anti-tumor therapy has not recovered to grade =1 (hematology and biochemistry meet the inclusion criteria 6 and 7); 9. Cumulative equivalent dose of corticosteroids equivalent to =140 mg of prednisone (excluding pre-treatment) within 14 days prior to the first dose of investigational drug; 10. Received any of the following treatments: (1) Received allogeneic stem cell transplantation within 6 months before the first dose of the investigational drug. Patients who have undergone allogeneic transplantation must have been off all immunosuppressive agents for 6 weeks and have no signs or symptoms of graft-versus-host disease (GVHD); (2) Autologous stem cell transplantation within 12 weeks before the first dose of the investigational drug; 11. Central nervous system (CNS) involvement or clinical signs and symptoms of multiple myeloma involvement of the meninges. If either of the two is suspected, a negative whole brain magnetic resonance imaging (MRI) and lumbar puncture cytology are required; 12. Confirmed plasma cell leukemia (per standard classification, peripheral circulating plasma cells =5%), Waldenstrom macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M protein], and skin lesions), or primary light chain amyloidosis; 13. Patients with a history of other malignant tumors within 5 years before signing informed consent (except for cured basal cell skin cancer, cervical carcinoma in situ, and papillary thyroid carcinoma); 14. Known allergic reaction, hypersensitivity reaction or intolerance to the investigational drug or its excipients; 15. Lun
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Minimal Residual Disease (MRD);ORR; | — |
Countries
China
Contacts
Public ContactAn Gang
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.
Outcome results
None listed