Back to results

CAR-T Cells Therapy in Relapsed/Refractory Multiple Myeloma (MM)

Primary Purpose

Relapsed/Refractory Multiple Myeloma(MM)

Status

Terminated

Phase

Not Applicable

Locations

China

Study Type

Interventional

Intervention

CART therapy in Relapsed/Refractory multiple myeloma

About this trial

This is an interventional treatment trial for Relapsed/Refractory Multiple Myeloma(MM) focused on measuring BCMA-CART, CD138-CART, CD56-CART, CD38-CART

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Relapsed/Refractory MM patients
Cell phenotype is BCMA/CD138/CD38/CD56 positive (single or combined) ,and minimal residual disease (MRD) was positive(cytology, genetic testing)
Estimated survival time is more than 3 months in multiple myeloma,and Karnofsky performance status(KPS) score is more than 60.
No cytapheresis and cell separation contraindication.
Hemoglobin is more than 80 gram per litre.
The function of important organ was satisfied:(1)cardiac ultrasound indicated that cardiac ejection fractions is more than 50%（EF≥50%）, and the electrocardiogram showed no obvious abnormality;(2)Blood oxygen saturation is more than 90%（SpO2≥90%）;(3)Creatinine（Cr） is less than 2.5 times normal range;(4)Alanine transaminase（ALT） and glutamic-oxalacetic transaminase（AST）is less than 3 times normal range,and total bilirubin is less than 2 milligram per deciliter(TBil≤2.0mg/dL).
After discussion by the expert group, the patient's condition was analyzed and combined with the general physical condition of the patient, the benefit of participating in the clinical trial was greater than the risk.
Volunteered for this clinical trail and signed a consent form .

Exclusion Criteria:

Patients with high tumor burden or progression of disease need to control the progression of disease in order to decrease the tumor burden.
Patients with active infection and fever.
Patients' neutrophilic granulocyte has decreased more than 10 days,and is difficult to control after treatment.
Patients are infected with fungus,bacteria or virus,and are difficult to control after treatment.
Patients with infection of HIV or with actively infection of Hepatitis B Virus(HBV) or Hepatitis C Virus(HCV).
Pregnant or lactating women.
Patients with severe insufficient cardiac, pulmonary and hepatorenal functions.
Patients had been treated with cell therapy but was invalid.After analyzing the patient's condition , the expert group think that the patient doesn't fit to attend the therapy of CART.
The monoclonal antibodies of BCMA or CD38 are invalid for the patients who have used the drug.
Any situation may do harm to the subjects or interfere the results.
After allogeneic transplantation, patients are more than 3 degrees of acute Graft-Versus-Host disease(GVHD).

Sites / Locations

Southern Medical University Zhujiang Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CART therapy in multiple myeloma

Arm Description

In order to assess the safety and validity of using CAR-T therapy refractory/rela-psed multiple myeloma patients with one kind of BCMA-CART,CD138-CART,CD56-CART or CD38-CART,subjects will receive 10^6-10^7/Kg transduced CAR T cells at one time.

Outcomes

Primary Outcome Measures

Adverse events that Are related to treatment

Determine the toxicity profile of the BCMA/CD138/CD38/CD56-targeted CAR-T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0

Secondary Outcome Measures

Estimate 2 year overall survival(OS) after infusion of BCMA/CD138/CD38/CD56-CART and sequential treatment

To estimate 2 year overall survival(OS) after BCMA/CD138/CD38/CD56-CART infusion and sequential treatment with Relapsed/Refractory MM

Estimate 2 year relapse rate after infusion of BCMA/CD138/CD38/CD56-CART and sequential treatment

To estimate 2 year relapse rate after BCMA/CD138/CD38/CD56-CART infusion and sequential treatment with Relapsed/Refractory MM

Estimate 2 year progression free survival after infusion of BCMA/CD138/CD38/CD56-CART and sequential treatment

To estimate 2 year progression free survival after BCMA/CD138/CD38/CD56-CART infusion and sequential treatment with Relapsed/Refractory MM

Full Information

NCT ID

NCT03473496

First Posted

March 15, 2018

Last Updated

September 17, 2021

Sponsor

Zhujiang Hospital

Collaborators

Nanfang Hospital, Southern Medical University, The Third Affiliated Hospital of Southern Medical University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

1. Study Identification

Unique Protocol Identification Number

NCT03473496

Brief Title

CAR-T Cells Therapy in Relapsed/Refractory Multiple Myeloma

Acronym

Official Title

The Prospective, Multi-center And Single-arm Clinical Study of Chimeric Antigen Receptor T(CAR-T) Cells Therapy in Relapsed/Refractory Multiple Myeloma

Study Type

Interventional

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Terminated

Why Stopped

After CAR-T treatment, the benefit is not significant, and it is difficult to enroll.

Study Start Date

March 1, 2018 (Actual)

Primary Completion Date

January 31, 2020 (Actual)

Study Completion Date

January 31, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Zhujiang Hospital

Collaborators

Nanfang Hospital, Southern Medical University, The Third Affiliated Hospital of Southern Medical University, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Multiple myeloma（MM） is one of the most common malignant diseases in the blood system.There is still no cure for the disease which only control the development of the disease in various ways.Chimeric Antigen Receptor-transduced T cell (CAR-T) therapy is one of revolutionary targeted immunotherapy.The efficacy of CAR-T cells for the treatment of acute B lymphocytic leukemia has been widely recognized, and several clinical trials have been reported in the treatment of multiple myeloma with CAR-T cells.

Detailed Description

Multiple myeloma（MM） is one of the most common malignant diseases in the blood system.There is still no cure for the disease which only control the development of the disease in various ways. In recent years, the understanding of pathogenic molecular mechanism in MM , many new types of drugs can be used in the treatment of this disease, one of the most widely used is proteasome inhibitors and immune regulator.Hematopoietic stem cell transplantation has also been shown to improve complete remission rates and prolong patient survival.Combined with the advantages of multiple therapies, chimeric antigen receptor T cells (CAR-T) have gradually become one of the strongest and most powerful weapons against multiple myeloma. CAR - T cells was taken in the form of genetic modification, and specific identified target antigen monoclonal antibody of single variable region (scFv) expression in T cell surface, and coupled with the activation of intracellular proliferation signal domain. When scFv recognizes antigens expressed in malignant cells, it stimulates the activation signal of downstream T cells and produces specific killing effects. CAR-T therapy is one of revolutionary targeted immunotherapy.The efficacy of CAR-T cells for the treatment of acute B lymphocytic leukemia has been widely recognized, and several clinical trials have been reported in the treatment of multiple myeloma with CAR-T cells.Throughout registration of clinical trials and published research results, B-cell maturation antigen (BCMA) as one of targets , its effect is more significant than other molecules.As with BCMA antigens, cluster of differentiation 138(CD138), cluster of differentiation 56 (CD56) or cluster of differentiation 38(CD38) antigens are also highly expressed in multiple myeloma cells.With CD138 as the target for the treatment of CAR-T cells, several clinical studies have been registered, and the results show that some of them are effective. In order to lay a foundation for the application of relapsed/refractory multiple myeloma patients with CAR-T therapy，objects are refractory/ relapsed patients with multiple myeloma,and plans to into the group of the number of cases in 50 cases.The main content is safety, efficacy and feasibility analysis of the CAR-T cells （single CAR-T or double CAR-T cells with BCMA、CD138、CD56 or CD38 ) in the treatment of refractory/relapsed multiple myeloma.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Relapsed/Refractory Multiple Myeloma(MM)

Keywords

BCMA-CART, CD138-CART, CD56-CART, CD38-CART

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

2 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CART therapy in multiple myeloma

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

CART therapy in Relapsed/Refractory multiple myeloma

Intervention Description

one kind of BCMA/CD138/CD38/CD56-CART therapy in Relapsed/Refractory multiple myeloma

Primary Outcome Measure Information:

Title

Adverse events that Are related to treatment

Description

Determine the toxicity profile of the BCMA/CD138/CD38/CD56-targeted CAR-T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Estimate 2 year overall survival(OS) after infusion of BCMA/CD138/CD38/CD56-CART and sequential treatment

Description

To estimate 2 year overall survival(OS) after BCMA/CD138/CD38/CD56-CART infusion and sequential treatment with Relapsed/Refractory MM

Time Frame

2 years

Title

Estimate 2 year relapse rate after infusion of BCMA/CD138/CD38/CD56-CART and sequential treatment

Description

To estimate 2 year relapse rate after BCMA/CD138/CD38/CD56-CART infusion and sequential treatment with Relapsed/Refractory MM

Time Frame

2 years

Title

Estimate 2 year progression free survival after infusion of BCMA/CD138/CD38/CD56-CART and sequential treatment

Description

To estimate 2 year progression free survival after BCMA/CD138/CD38/CD56-CART infusion and sequential treatment with Relapsed/Refractory MM

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Relapsed/Refractory MM patients Cell phenotype is BCMA/CD138/CD38/CD56 positive (single or combined) ,and minimal residual disease (MRD) was positive(cytology, genetic testing) Estimated survival time is more than 3 months in multiple myeloma,and Karnofsky performance status(KPS) score is more than 60. No cytapheresis and cell separation contraindication. Hemoglobin is more than 80 gram per litre. The function of important organ was satisfied:(1)cardiac ultrasound indicated that cardiac ejection fractions is more than 50%（EF≥50%）, and the electrocardiogram showed no obvious abnormality;(2)Blood oxygen saturation is more than 90%（SpO2≥90%）;(3)Creatinine（Cr） is less than 2.5 times normal range;(4)Alanine transaminase（ALT） and glutamic-oxalacetic transaminase（AST）is less than 3 times normal range,and total bilirubin is less than 2 milligram per deciliter(TBil≤2.0mg/dL). After discussion by the expert group, the patient's condition was analyzed and combined with the general physical condition of the patient, the benefit of participating in the clinical trial was greater than the risk. Volunteered for this clinical trail and signed a consent form . Exclusion Criteria: Patients with high tumor burden or progression of disease need to control the progression of disease in order to decrease the tumor burden. Patients with active infection and fever. Patients' neutrophilic granulocyte has decreased more than 10 days,and is difficult to control after treatment. Patients are infected with fungus,bacteria or virus,and are difficult to control after treatment. Patients with infection of HIV or with actively infection of Hepatitis B Virus(HBV) or Hepatitis C Virus(HCV). Pregnant or lactating women. Patients with severe insufficient cardiac, pulmonary and hepatorenal functions. Patients had been treated with cell therapy but was invalid.After analyzing the patient's condition , the expert group think that the patient doesn't fit to attend the therapy of CART. The monoclonal antibodies of BCMA or CD38 are invalid for the patients who have used the drug. Any situation may do harm to the subjects or interfere the results. After allogeneic transplantation, patients are more than 3 degrees of acute Graft-Versus-Host disease(GVHD).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yanjie He

Organizational Affiliation

Zhujiang Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Southern Medical University Zhujiang Hospital

City

Guangdong

State/Province

Guangdong

ZIP/Postal Code

510000

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Learn more about this trial

CAR-T Cells Therapy in Relapsed/Refractory Multiple Myeloma

We'll reach out to this number within 24 hrs