Dual-target CAR-T Cells (C-4-29) in the Treatment of Relapsed/Refractory Multiple Myeloma

Phase I Clinical Study of CAR-T Cells (C-4-29) in the Treatment of Patients With Relapsed/Refractory Multiple Myeloma

This is a phase I clinical study to evaluate the safety and tolerability of C-4-29 in patients with relapsed or refractory multiple myeloma, and to obtain the maximum tolerated dose of C-4-29 and phase II Recommended dose.

Study Overview

• Status: Enrolling by invitation
• Conditions: Multiple Myeloma in Relapse; Multiple Myeloma, Refractory
• Intervention / Treatment: Biological: C-4-29 Cells

Detailed Description

This is a multi-center, single-arm, open-label study. The study plans to set up 3 dose groups, adopting a dose-escalating 3+3 design, and plan to recruit about 9-18 subjects with relapsed or refractory multiple myeloma.C-4-29 cells will be infused to the subject by intravenous infusion.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥18 years old, no gender limit;
2. Diagnosed with multiple myeloma according to the IMWG diagnostic criteria.
3. Received third-line and above regular treatments (including proteasome inhibitors or immunomodulators) that are ineffective or intolerable;

4. The disease is measurable during screening:

   1. Serum M protein level ≥0.5g/dL, or urine M protein level ≥200mg/24h;
   2. Or light chain type MM with undetectable serum or urine disease: serum immunoglobulin free light chain ≥10mg/dL and serum immunoglobulin κ/γ free light chain ratio is abnormal;
   3. Or evaluable extramedullary lesions with the largest transverse diameter ≥ 1 cm.
5. ECOG 0～2 points;
6. The expected survival time is more than 12 weeks;
7. No serious mental disorders;

8. The function of important organs is basically normal:

   1. Heart function: echocardiography indicates that the cardiac ejection fraction is ≥50%, and the electrocardiogram has no obvious abnormalities;
   2. Renal function: serum creatinine≤2.0×ULN;
   3. Liver function: ALT and AST ≤3×ULN;
   4. Total bilirubin and alkaline phosphatase≤2×ULN (Gilbert syndrome≤3.0×ULN);
   5. Blood oxygen saturation>92%.
9. Have standards for apheresis or venous blood collection, and no other cell collection contraindications;
10. The subject agrees to use reliable and effective contraceptive methods for contraception within 1 year after signing the informed consent form to receiving C-4-29 cell infusion (excluding safe period contraception).
11. The patient himself or his guardian agrees to participate in the clinical trial and signs the ICF, indicating that he understands the purpose and procedures of the clinical trial and is willing to participate in the research.

Exclusion Criteria:

1. Have received CAR-T therapy or other genetically modified cell therapy;
2. With central nervous system disease at the time of screening ;
3. Participated in other clinical studies within 1 month before screening;
4. Have received a live attenuated vaccine within 4 weeks before screening;
5. Have received the following anti-tumor treatments before apheresis: received chemotherapy, targeted therapy or other experimental drug treatments within 14 days or at least 5 half-lives (whichever is shorter);
6. Within 7 days before apheresis, there are active infections or uncontrollable infections that require systemic treatment (except CTCAE grade 1 genitourinary system infection and upper respiratory tract infection);
7. Suffered from plasma cell leukemia at the time of screening ;
8. Suffered from other malignant tumors other than multiple myeloma within 3 years before screening, except for the following cases: malignant tumors that have received radical treatment, and there is no known active disease for ≥3 years before enrollment; or fully treated non-melanoma skin cancer with no evidence of disease;
9. Except for hair loss or peripheral neuropathy, the toxicity of previous anti-tumor treatments has not improved to the baseline level or ≤grade 1;
10. Subjects who have received systemic steroid treatment within 7 days before apheresis or who have been determined by the investigator to require long-term systemic steroid treatment during treatment (except for inhaled or topical use);

11. Suffered from any of the following heart diseases:

    1. NYHA stage III or IV congestive heart failure;
    2. Myocardial infarction or CABG occurred ≤6 months before enrollment;
    3. Clinically significant ventricular arrhythmia, or history of unexplained syncope (except for cases caused by vasovagal or dehydration);
    4. History of severe non-ischemic cardiomyopathy.
12. Active autoimmune diseases;
13. HBsAg or HBcAb positive and HBV DNA is greater than the normal range; HCV antibody is positive and HCV RNA greater than the normal range; HIV antibody positive; syphilis positive; CMV DNA positive;
14. Have experienced a venous embolism event (for example: pulmonary embolism or deep vein thrombosis) and requires anticoagulation therapy or the subject meets the following conditions: a. Bleeding of grade 3 to 4 lasting more than 30 days; b. Have sequelae caused by venous thrombosis (such as persistent dyspnea and hypoxia);
15. Women who are pregnant or breastfeeding, and male or female subjects who plan to have children within 1 year after receiving C-4-29 cell reinfusion;
16. Other situations considered by the researcher to be unsuitable to participate in the study.

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: C-4-29 cells; Infusion of C-4-29 cells by dose-escalating	Biological: C-4-29 Cells; Drug: C-4-29 Cells； Administration method: intravenous infusion； Subjects will be treated with Fludarabine and Cyclophosphamide before cell infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse events after C-4-29 infusion [Safety and Tolerability]	Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)	28 days
Obtain the maximum tolerated dose of C-4-29 cells[Safety and Tolerability]	Dose-limiting toxicity after cell infusion	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate after C-4-29 infusion [Effectiveness]	Objective response rate includes sCR, CR, VGPR, PR, MR	3 months
AUCS of C-4-29 cells [Cell dynamics]	AUCS is defined as the area under the curve in 28 days	3 months
CMAX of C-4-29 cells [Cell dynamics]	CMAX is defined as the highest concentration of C-4-29 cells expanded in peripheral blood	3 months
TMAX of C-4-29 cells [Cell dynamics]	TMAX is defined as the time to reach the highest concentration	3 months
Peripheral blood M protein contents after C-4-29 infusion [Cell dynamics]	Periodic detection of Peripheral blood M protein after cell infusion	3 months
Urine Bence-Jones protein contents after C-4-29 infusion [Cell dynamics]	Periodic detection of Urine Bence-Jones protein after cell infusion	3 months
Immunogenicity of C-4-29 cells	Anti-CAR antibody	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival after C-4-29 infusion	OS is defined as the time from C-4-29 cell infusion to death due to any cause	2 years
Progression-free survival after C-4-29 infusion	PFS is defined as the time from the start of the C-4-29 infusion to the first disease progression or death from any cause	2 years
Duration of relief after C-4-29 infusion	DOR is defined as the time from reaching MR or better to disease progression or death from any cause	2 years

Collaborators and Investigators

• Sponsor: Chongqing Precision Biotech Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2021
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): July 18, 2024

Study Registration Dates

• First Submitted: April 6, 2021
• First Submitted That Met QC Criteria: April 25, 2021
• First Posted (Actual): April 27, 2021

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 16, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Myeloma; CAR-T
• 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: PB04

Drug and device information, study documents

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