A Phase I Clinical Trial to Evaluate CART-BCMA in Patients With Relapsed and/or Refractory Multiple Myeloma

Shanghai Simnova Biotechnology Co.,Ltd.2 sites in 1 country15 target enrollmentMarch 12, 2021

ConditionsMultiple Myeloma

InterventionsCART-BCMA

DrugsCART-BCMA

Overview

Phase: Phase 1
Intervention: CART-BCMA
Conditions: Multiple Myeloma
Sponsor: Shanghai Simnova Biotechnology Co.,Ltd.
Enrollment: 15
Locations: 2
Primary Endpoint: BCMA-CART Maximum Tolerable Dose (MTD) and/or Recommends Dose (RD)
Status: Active, not recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a Phase 1, multicenter, open-label study o evaluate the safety and efficacy of CART-BCMA in subjects with relapsed/refractory multiple myeloma.

Detailed Description

The study will consist of 2 parts: dose-escalation (Part A) and dose-expansion (Part B). The dose-escalation part (Part A) of the study is to evaluate the safety and tolerability of increasing dose levels of CART-BCMA to establish a recommended dose (RD); and the dose-expansion part (Part B) of the study is to further evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of CART-BCMA at the RD.

Registry

clinicaltrials.gov

Start Date

March 12, 2021

End Date

December 31, 2024

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shanghai Simnova Biotechnology Co.,Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•At least 18 years old (inclusive), gender is not limited;
•Multiple myeloma patients who have received at least 3-line previous multiple myeloma therapy and have failed at least through proteasome inhibitors and immunomodulators; Each line of treatment has at least 1 complete treatment cycle, unless the best remission for the treatment is recorded as disease progression (PD) (according to the IMWG Efficacy Evaluation Criterialpublished in 2016, Appendix 4); PD must be recorded during or within 12 months after the last treatment;
•Bone marrow specimens were confirmed by immunohistochemistry or flow cytometry as positive BCMA expression in plasma cells and myeloma cells (\>5%);
•The presence of measurable lesions during screening was defined as any of the following:
•Serum M protein ≥1 g/dL (≥10 g/L); Urinary M protein level ≥200 mg/24 h; Serum light chain (FLC) : abnormal serum FLC ratio (\< 0.26 or \> 1.65), and affected FLC≥10 mg/dL (100mg/L);
•ECOG score (Appendix 1) 0\~1;
•Expected survival time ≥3 months;
•The mononuclear cells meet the following standards within 3 days before collection:
•Hematology:≥0.5×109/L\[The use of past granulocyte colony stimulating factor (G-CSF) is allowed, but patients shall not receive this supportive treatment within 7 days prior to the screening phase of laboratory examination\];≥1.0 ×109 /L\[Ex-granulocyte colony-stimulating factor (G-CSF) is allowed, but subjects shall not receive this supportive treatment within 7 days prior to the screening laboratory examination\];Subjects' platelet count ≥50×109/L (Subjects shall not receive blood transfusion support within 7 days before the screening laboratory examination);≥8.0 g/dL (Recombinant Human Erythropoietin is allowed) \[Subjects have not received a red blood cell infusion (RBC) within 7 days prior to the screening phase laboratory examination\]; Heart:Left ventricular ejection fraction (LVEF) ≥ 50%; Lung:Blood oxygen saturation ≥91% under non-inhaled oxygen condition; Kidney:Creatinine clearance (CRCL) or glomerular filtration rate (GFR) (Cockcroft-Gault formula) ≥30 mL/min; Liver:Total bilirubin (serum) ≤1.5 × ULN;Gilbert's disease patients with \>1.5 × ULN could be enrolled with the consent of the Sponsor; Blood coagulation:Plasma prothrombin time (PT) ≤1.5 × ULN, international standardized ratio (INR) ≤1.5 × ULN, partial prothrombin time (APTT) ≤1.5 × ULN;
•Peripheral venous access can meet the needs of single collection and intravenous drip;

Exclusion Criteria

•Subjects who are known to have allergic reactions, hypersensitivity, intolerance, or contraindications to any component of CART-BCMA or any drugs that may be used in the study (including fludarabine, cyclophosphaamide, or tozumab), or who are allergic to β-lactam antibiotics, or who have had severe allergic reactions in the past;
•Prior to any CAR-T therapy or BCMA-targeted therapy;
•Have received the following anti-MM treatment within the prescribed time range before single calyzer:
•Has received small molecule targeted therapy within 4 weeks or 5 half-lives, whichever is longer; treatment with a large molecule within 4 weeks or 2 half-lives, whichever is longer; received cytotoxic therapy, proteasome inhibitor, or modern Chinese medicine preparation with anti-tumor effect within 2 weeks; received immunomodulatory drug therapy within 1 week; received radiotherapy within 1 week
•Participated in a clinical trial within 4 weeks before the single collection;
•Patients who received autologous hematopoietic stem cell transplantation (ASCT) or previous allogeneic stem cell transplantation within 12 weeks before a single collection (no time limit);
•People who received live vaccine or attenuated vaccine within 4 weeks before the CART-BCMA harvest; Note: Inactivated viral vaccines for seasonal influenza are allowed for injection; Intranasally administered live attenuated influenza vaccines are not allowed;
•Received any of the following treatments within 7 days prior to the single collection or as determined by the investigator to require long-term treatment during the study period:
•Systemic steroid therapy (except inhalation or topical use), Immunosuppressive therapy, Graft versus host therapy, Preventive treatment of central nervous system
•Incomplete recovery or stabilization to grade 1 (NCI-CTCAE v5.0) of toxicity (including peripheral neuropathy) caused by previous treatment;

Arms & Interventions

Subjects will receive CART-BCMA

Biological: CART-BCMA Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) to produce CART-BCMA. During CART-BCMA production, subjects may receive bridging chemotherapy for disease control. Upon successful generation of CART-BCMA product, subjects will receive treatment with CART-BCMA therapy. Study treatment will include lymphodepleting chemotherapy followed by one dose of CART-BCMA administered by intravenous (IV) injection.

Intervention: CART-BCMA