Evaluating CAR-T therapy for newly diagnosed multiple myeloma patients

CAR-T Injection in Transplant In-Eligible Newly Diagnosed Multiple Myeloma Patients

This study is testing a new CAR-T therapy to see if it can help people who have just been diagnosed with multiple myeloma feel better and improve their treatment outcomes.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai Changzheng Hospital (Academic / other)
• Drugs / interventions: CAR-T, radiation
• Locations: 1 site (Shanghai, Shanghai)
• Trial ID: NCT05840107 on ClinicalTrials.gov

What this trial studies

This clinical trial is a single-arm, open-label study designed to assess the safety and efficacy of the CAR-T therapy GC012F in patients with newly diagnosed multiple myeloma (NDMM). A total of 9-18 participants will undergo apheresis and receive two cycles of induction therapy before or after the apheresis, followed by a single infusion of CAR-T. Efficacy will be evaluated through various assessments at 1, 3, and every 3 months thereafter for up to 2 years, with a focus on monitoring adverse events and treatment responses. The study aims to provide insights into the potential benefits of CAR-T therapy in this patient population.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with documented evidence of multiple myeloma meeting specific diagnostic criteria.

Not a fit: Patients with smoldering myeloma or those who do not meet the defined criteria for multiple myeloma may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could offer a new treatment option that significantly improves outcomes for patients with newly diagnosed multiple myeloma.

How similar studies have performed: Other studies have shown promising results with CAR-T therapies in hematological malignancies, suggesting potential success for this approach in treating multiple myeloma.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 when signing informed consent form（ICF）
2. Documented evidence of multiple myeloma at diagnosis as defined by IMWG guidelines ,monoclonal plasma cells in the bone marrow ≥10% and/or serum M protein ≥ 3 g/dL and/or 24h urine light chain ≥ 500 mg and/or presence of a biopsy proven plasmacytomas, not meet evidence of Smoldering Myeloma with SLiM/CRAB syptoms, and meet at least 2 of a-c or meet d of the following criteria at screening:

   1. Serum M protein ≥ 2 g/dL;
   2. Serum involved / uninvolved free light chain ratio ≥ 20;
   3. Bone marrow involved with monoclonal plasma cells ≥20% ;
   4. With Cytogenetic high-risk markers.
3. Or documented evidence of multiple myeloma at diagnosis as defined by IMWG guidelines CRAB (calcium elevation, renal insufficiency, anemia, and bone abnormalities)/SLiM criteria, monoclonal plasma cells in the bone marrow ≥10% or presence of a biopsy proven plasmacytomas, and measurable secretory disease according to IMWG criteria meet one or more of the following criteria at screening:

   1. Serum M protein ≥ 1 g/dL;
   2. Urine M protein ≥ 200 mg/24h;
   3. Serum free light chain sFLC ≥ 10 mg/dL with abnormal serum immunoglobulin κ/λ free light chain ratio.
4. ECOG score was 0-3 at screen;
5. Estimated life expectancy ≥3 months;
6. Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L without use of growth factors;
7. Platelet count ≥ 50×10\^9/L without transfusion support within 7 days before the screen;
8. Hemoglobin≥ 60 g/L;
9. Adequate functional reserve of organs:

   1. ALT/AST ≤ 2.5× ULN(Upper Limit of Normal);
   2. Creatinine clearance ≥ 15mL/min;
   3. Serum total bilirubin ≤ 1.5×ULN, except in subjects with congenital bilirubinemia,then direct bilirubin ≤ 1.5×ULN;
   4. The left ventricular ejection fraction (LVEF)≥50%, and no clinically significant ECG abnormalities were found;
   5. Basic oxygen saturation in natural indoor air: SPO2\>92%.
10. Adequate venous access for apheresis collection, and no other contraindications to apheresis;
11. Subjects and sexual partner with fertility are willing to use effective and reliable method of contraception for at least 1 year after CAR-T cell infusion, serum HCG should be negative in females with fertility both at screening and baseline;
12. Subjects must sign a written informed consent.

Exclusion Criteria:

1. Patients who are transplant eligible high-risk patients and plan to adopt auto/allo-transplantation
2. Subject has had radiation therapy within 14 days of screening;
3. Subjects has plasma cell leukemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes);
4. Subjects has a diagnosis of primary amyloidosis, Waldenstroem's disease, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma;
5. Having other tumors (excluding non-melanoma skin cancer and cervical cancer in situ bladder cancer and breast cancer that have been disease-free for more than 5 years);
6. Evidence of serious mental disorders or changes in mental status, or the presence of central nervous system or diseases, such as seizures, cerebrovascular ischemia/hemorrhage, dementia, cerebellar diseases, or autoimmune diseases involving CNS;
7. History of hereditary diseases such as Fanconi anemia, Schrader syndrome, Costerman syndrome, or any other known bone marrow failure syndrome;
8. Clinically significant cardiac disease including: uncontrolled cardiac arrhythmia or clinically significant ECG abnormalities, grade III-IV heart failure or myocardial infarction cardiac angioplasty or stenting unstable angina or other clinically significant cardiac conditions within one year prior to enrollment;
9. Presence of any indwelling catheter or drainage tube (e.g., percutaneous nephrostomy catheter indwelling catheter bile drainage tube or pleural/peritoneal/pericardial catheter) The use of a dedicated central venous catheter is permitted;
10. Confirmed or suspected CNS involved;
11. A positive virological result for any of the following: HIV, HCV, HBsAg（If HBcAg positive, DNA copies must below the LOQ）, TPPA;
12. Other severe viral or bacterial infections or uncontrolled systemic fungal infections are present;
13. Severe allergic history or allergic constitution;
14. There is a history of an autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) that has resulted in terminal organ damage or requires systemic immunosuppressive/disease modulating drugs in the past 2 years;
15. Presence of lung disease (such as pulmonary fibrosis);
16. Subjects has had major surgery within 2 weeks before screen or has not fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study;
17. Poor compliance due to physiological, family, social, and geographical factors, etc., and inability to comply with the research program and follow-up plan;
18. Pregnant or lactating women;
19. Investigator assessment deemed to be ineligible.

Where this trial is running

Shanghai, Shanghai

• Shanghai Changzheng Hospital — Shanghai, Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Juan Du, MD — Shanghai Changzheng Hospital
• Study coordinator: Juan Du, MD

Conditions Multiple Myeloma