Evaluate CART-BCMA in Patients With Relapsed and/or Refractory Multiple Myeloma

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: CART-BCMA

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.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hangzhou, China
    • Hematology Department of the First Affiliated Hospital of Zhejiang University
  • Wuhan, China
    • Hematology Department of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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;
• The subject agrees to use reliable contraceptive methods for contraception within 1 year after signing the informed consent form to the infusion. Including but not limited to: abstinence, men undergoing vasectomy, implantable progesterone contraceptives that can inhibit ovulation; intrauterine contraceptive devices; hormone-releasing intrauterine devices; sexual partner sterilization methods; copper intrauterine devices, Correct use of proven compound hormonal contraceptives that can inhibit ovulation; progesterone contraceptives that can inhibit ovulation. At the same time, female subjects should promise not to donate eggs (egg cells, oocytes) for assisted reproduction within 1 year after the infusion;
• Volunteer to participate in clinical trials and sign Informed Consent Form;

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;
• MM is suspected to be involved in the central nervous system or meninges and confirmed by MRI or CT, or to have other active central nervous system diseases;
• Patients with plasma cell leukemia or Waldenstrom macroglobulinemia or POEMS syndrome (polyneuropathy, organ enlargement, endocrine disorder, monoclonal protein, and cutaneous disease) or amyloidosis at the time of screening;
• Heart disease: Existing heart failure (NYHA classification ≥II, Appendix 2), unstable angina pectoris, or severe heart disease as determined by the investigator; Myocardial infarction had occurred no more than 6 months before single arthroplasty. Had an episode of unstable angina pectoris, severe arrhythmia as determined by the researchers, or had undergone coronary artery bypass grafting (CABG) no more than 3 months before the single harvest;
• Poor control of hypertension (systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg) or with hypertensive crisis or hypertensive encephalopathy;
• Patients who had undergone major surgery or plasma separation other than diagnosis or biopsy within 4 weeks prior to the study alone, or who were expected to undergo major surgery during the study period; Note: Patients who plan to undergo surgery under local anesthesia may participate in the study. Kyphoplasty or vertebra osteoplasty are not considered major surgery;
• Receiving thrombolytic, anticoagulant or antiplatelet therapy;
• Infections require intravenous antibiotics or hospitalization;
• Patients with active hepatitis B; Hepatitis C virus (HCV) antibody positive; HIV-positive persons; Syphilis primary screening antibody positive; A) Inactive/asymptomatic patients with carryable, chronic, or active HBV who meet the following criteria are eligible for inclusion: HBV DNA <500 IU/mL (or 2500 copies /mL) at the time of screening.
• Women who are pregnant or lactating;
• The investigator considers that the subject is unsuitable to participate in this clinical study due to any abnormal clinical or laboratory examination or other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: CART-BCMA; The CART-BCMA (study drug) used in this study are chimeric antigen receptor specifically expressing T cells targeting BCMA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of all adverse events and serious adverse events	The safety and tolerability of CART-BCMA were evaluated according to the the incidence of all adverse events and serious adverse events	Day 1 through Month 24
BCMA-CART Maximum Tolerable Dose (MTD) and/or Recommends Dose (RD)	BCMA-CART Maximum Tolerable Dose (MTD) and/or Recommends Dose (RD)	Day 1 through Month 24

Collaborators and Investigators

• Sponsor: Shanghai Simnova Biotechnology Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2021
• Primary Completion (Actual): July 31, 2022
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: April 19, 2022
• First Submitted That Met QC Criteria: April 23, 2022
• First Posted (Actual): April 26, 2022

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: B03B00301-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No