Novel BCMA-targeted CAR-T Cell Therapy for Multiple Myeloma

This study evaluates the safety and efficacy of novel BCMA-targeted CAR-T cell therapy (CBG-002) for patients with relapsed or refractory multiple myeloma (r/r MM). CBG-002 is designed based on the fourth-generation of CAR-T techonology.

Study Overview

• Status: Recruiting
• Conditions: Relapsed or Refractory Multiple Myeloma
• Intervention / Treatment: Drug: Fludarabine; Biological: anti-BCMA CAR-T; Drug: Cyclophosphamid

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • Recruiting
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with relapsed/refractory multiple myeloma aged 18-75 years;
2. BCMA expression ≥50% in bone marrow samples confirmed by Flow Cytometry or IHC is positive for BCMA expression;

3. Relapsed/refractory patients who meet the following conditions:

   1. Ineffective or disease progression after receiving bortezomib (proteasome inhibitor) and lenalidomide for 3 courses;
   2. Ineffective or disease progression after receiving the original treatment plan for 3 courses;
   3. The interval between the last treatment and disease progression is more than 30 days;
   4. There is currently no indication for hematopoietic stem cell transplantation, or the patient refuses to do hematopoietic stem cell transplantation;
   5. The definition of disease progression refers to the "2014 IMWG Standards", and at least meets the following 1 items:

   e.1 Serum M protein ≥ 0.5 g/dL;

   e.2 Urine M protein ≥ 200 mg/24 h;

   e.3 If the serum FLC ratio is abnormal, the patient's FLC level ≥ 10 mg/dL (100 mg/L);

   e.4 Evaluable plasmacytoma confirmed by biopsy;

   e.5 Increase in the proportion of bone marrow plasma cells ≥25% (absolute increase ≥10%);

   e.6 Bone marrow plasma cells account for 30% of the total bone marrow cells;

4. Estimated survival time> 12 weeks;

5. The disease status can be assessed and meet at least one of the following:

   1. Serum M-protein ≥10 g/L;
   2. 24h urine M-protein ≥200mg;
   3. Serum FLC≥5mg/dL;
   4. Plasma cell tumors that can be assessed by testing or images;
   5. The proportion of bone marrow plasma cells ≥ 30%;
6. ECOG physical status score 0-1;
7. Have enough venous access for apheresis or venous blood collection, and there are no other contraindications for blood cell separation;
8. WBC ≥ 1.5×109/L; PLT ≥ 45×109/L;
9. Serum creatinine ≤ 1.5 upper limit of normal (ULN) ;
10. ALT ≤ 2.5 ULN, AST ≤ 2.5 ULN.

All laboratory test results within the above range should have no ongoing continuous supportive treatment.

Exclusion Criteria:

-

Subjects who meet any of the following criteria cannot be selected for this study:

1. Systemic treatment such as lymphatic depletion with cyclophosphamide and fludarabine within 2 weeks before enrollment or single cell collection, or cell therapy within 8 weeks before treatment;
2. HCV or HIV positive; any uncontrollable active infection, including active tuberculosis, HBV DNA level ≥1×103 copies/mL;
3. Active infections occurred within 72 hours before cleansing; as long as there is no evidence of active infection and antibiotics are not in the list of prohibited drugs, subjects who continue to use preventive antibiotics, antifungal drugs or antiviral drugs are not excluded;
4. The current systemic use of cyclosporine or steroid drugs such as dexamethasone, recent or current use of inhaled steroids is not excluded;
5. Renal insufficiency, serum creatinine>1.5 upper limit of normal (ULN);
6. Liver insufficiency, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT)>2.5 times ULN and direct bilirubin>1.5 times ULN;
7. Hyponatremia, blood sodium <125 mmol/L;
8. Baseline serum potassium <3.5 mmol/L (potassium supplementation can be given before participating in the study, and serum potassium recovery above this standard is not excluded);
9. Pregnant or lactating women;
10. Other serious diseases that may restrict subjects from participating in this trial (such as central nervous system disease, severe heart insufficiency, myocardial obstruction or unstable arrhythmia or unstable angina, gastric ulcer in the past 6 months , Active autoimmune diseases, etc.).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Anti-BCMA CAR-T (CBG-002); All subjects were intravenous administrated with CBG-002.	Drug: Fludarabine; 30mg/m2/d; Biological: anti-BCMA CAR-T; Retroviral vector-transduced autologous T cells to express anti-BCMA CAR.; Other Names: CBG-002 CAR-T; Drug: Cyclophosphamid; 300mg/m2/d

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of grade 3 or 4 treatment related adverse effect	All the CAR-T treatment related adverse events，including Dose limiting toxicity (DLT), cytokine release syndrome (CRS), CAR-T associated encephalopathy syndrome, will be assessed and graded by NCI CTCAE v 5.0.	24 weeks after last dose of CAR-T treatment
Overall response rate (ORR) after treated by CAR-T treatment	ORR will be assessed and graded by the international Myeloma Working Group (IMWG) Unified response criteria for multiple myeloma	up to 2 years after CAR-T treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of CAR-T cells (implantation endpoint)	To assess the duration of CAR-positive T cells in circulation, the copy number of CAR DNA was measured at the preset follow-up time point. The time when the results of any two consecutive tests were negative, were recorded as the "implantation endpoint".	up to 2 years after CAR-T treatment
Overall survival	From date of inclusion to date of progression, relapse, or death from any cause.	up to 2 years after CAR-T treatment
Progression free survival	The length of time that a participant's disease did not progress during and after CAR-T treatment.	up to 2 years after CAR-T treatment

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Carbiogene Therapeutics Co. Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2021
• Primary Completion (ANTICIPATED): October 1, 2023
• Study Completion (ANTICIPATED): April 1, 2024

Study Registration Dates

• First Submitted: December 3, 2020
• First Submitted That Met QC Criteria: January 11, 2021
• First Posted (ACTUAL): January 13, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2023
• Last Update Submitted That Met QC Criteria: February 2, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: BCMA; Adoptive cell therapy; Chimeric antigen receptor T cell
• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: IR2020001474

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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