Study of FasT CAR-T GC012F Injection NDMM Patients

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05840107
• Other study ID #: GC012F-322
• Status: Recruiting
• Phase: Early Phase 1
• Start date: May 4, 2023
• Est. completion date: September 30, 2025

Study information

• Verified date: February 2024
• Source: Shanghai Changzheng Hospital
• Contact: Juan Du, MD
• Phone: +86-21 -81885423
• Email: changzheng_pg[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a single-arm, single-center, open-label clinical study to evaluate the safety and efficacy of CAR-T in patients with NDMM.

Description:

9-18 evaluable subjects are planned to be enrolled in this study. Apheresis will be carried out in subjects who meet eligible criteria, and total 2 cycles of induction therapy (three-drug combination regimen based on bortezomib with details determined by the investigator according to the patient's condition) will be selectively given to subjects before or after apheresis. Next, subjects will receive a single infusion of CAR-T, and the efficacy assessments will be performed at 1st month, 3rd months, and every 3 months within 2 years until the end of the trial (MRD testing is required for each efficacy assessment) 1.Efficacy assessments performed at the 1st month after infusion: 1.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ?/? 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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• GC012F injection
GC012F injection is an autologous dual CAR-T targeted BCMA and CD19. A single infusion of CAR-T cells will be administered intravenously

Locations

Country	Name	City	State
China	Shanghai Changzheng Hospital	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Changzheng Hospital	Gracell Biotechnology Shanghai Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events (AE) after CAR-T infusion	An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cellassociated neurotoxicity syndrome (ICANS). CRS and ICANS should be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading	Up to 1 year after patients infused with CAR-T injection
Primary	Percentage of patients with complete response (CR) and stringent complete response (sCR) after infusion		Up to 2 years after patients infused with CAR-T injection
Primary	overall response rate (ORR)	ORR defined as proportion of patients achieving PR or better based on IMWG defined response criteria	Up to 2 years after patients infused with CAR-T injection
Primary	Percentage of patients with minimal residual disease (MRD) negative in CR/sCR patients at landmark analysis	MRD negative rate	Up to 2 years after patients infused with CAR-T injection
Primary	Progress free survival (PFS)	PFS is defined as the time interval from the initiation of induction therapy until disease progression or death (for any reason).	Up to 2 years after patients infused with GC01 2F injection
Primary	Duration of response (DOR) after CAR-T infusion	DOR is defined as the time interval from the first assessment of sCR, CR, VGPR or PR to the first assessment of PD or death from any cause after CAR T infusion.	Up to 2 years after patients infused with GC01 2F injection