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Safety and Efficiency Study of BCMA-PD1-CART Cells in Relapsed/Refractory Multiple Myeloma

Primary Purpose

Multiple Myeloma

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

BCMA-PD1-CART Cell

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring BCMA, Myeloma, PD-1, Immunotherapy, Plasmocytoma, Chimeric antigen receptor T cell, Chimeric antigen receptor, B cell maturation antigen

Eligibility Criteria

14 Years - 80 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female, aged 14 to 80 years (including 14 and 80 years old).
The diagnosis was Refractory/relapsed multiple myeloma.(Meeting 1 of the follow 3 items)
A.Primary treatment patients with no effect after first and second line treatment.
B.Patients who relapsed after complete remission and failed to respond to two kind of therapy.
C.the predicted survival is more than three months.
Flow cytometry or immunohistochemistry showed BCMA positive in tumor cells.
Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.
No serious concomitant disease and major organ function is not serious abnormal.
No serious concomitant disease and major organ function is not serious abnormal.
the test meets the following indicators:

A.ALT/AST < 2.5 times the upper limit of normal (ULN) and total bilirubin≤34.2μmol/L.

B.WBC≥2.5×109/L.

C.PT/INR < 1.7 or PT was extended by less than 4 seconds.

Exclusion Criteria:

Women who are pregnant or breastfeeding.
Transduced positive T lymphocytes < 5% or amplified against CD3/CD28 stimulation < 5 times.
Active hepatitis B or hepatitis C, HIV/AIDS infection, any uncontrolled active infection.
Patients who are using steroid drugs throughout the body currently.
Patients who have received any gene therapy in the past.
Patients who are allergy to immunotherapy and related drugs.
Patients with heavy heart disease or poorly controlled high blood pressure.
Patients who received chemotherapy or radiation 4 weeks before the study began.
Patients who are participating in other clinical trials.

Sites / Locations

Hainan Hospital of Chinese PLA General HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

multiple myeloma

Arm Description

This study is to evaluate the efficacy and safety of BCMA-PD1-CART cells therapy for patients with Relapsed/Refractory Multiple Myeloma.

Outcomes

Primary Outcome Measures

Incidence of Treatment-related Adverse Events

Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0).

Secondary Outcome Measures

Overall Remission Rate(ORR) of BCMA-PD1-CART cells in Lymphoma

ORR will be assessed from the first CAR-T cell infusion to death or last follow-up

Overall survival(OS) of BCMA-PD1-CART cells in Lymphoma

OS will be assessed from the first CAR-T cell infusion to death or last follow-up

Progress-free survival(PFS) of BCMA-PD1-CART cells in Lymphoma

PFS will be assessed from the first CAR-T cell infusion to death or last follow-up

Rate of BCMA-PD1-CARTcells in peripheral blood cells

In vivo (peripheral blood) rate of BCMA-PD1-CARTcells were determined by means of flow cytometry.

Quantity of BCMA-PD1-CART cells copies in peripheral blood cells.

In vivo (peripheral blood) quantity of BCMA-PD1-CART cells copies copies were determined by means of qPCR.

Full Information

NCT ID

NCT04162119

First Posted

November 11, 2019

Last Updated

November 14, 2019

Sponsor

Chinese PLA General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04162119

Brief Title

Safety and Efficiency Study of BCMA-PD1-CART Cells in Relapsed/Refractory Multiple Myeloma

Official Title

Safety and Efficiency Study of BCMA-PD1-CART Cells in Relapsed/Refractory Multiple Myeloma

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Unknown status

Study Start Date

July 7, 2019 (Actual)

Primary Completion Date

October 10, 2021 (Anticipated)

Study Completion Date

October 10, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chinese PLA General Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

This is a single center, non-randomized, open-label, phase 2 study to evaluate the efficacy and safety of BCMA-PD1-CART cells therapy for patients with relapsed/refractory Multiple Myeloma.

Detailed Description

Previous studies have found that multiple myeloma cells express PD-L1 at a high level. Therefore, the combination of anti-PD-1 or PD-L1 antibodies with CART therapy may further improve the clinical efficacy of CART cell for multiple myeloma. The investigators screened PD-1 mutant that have high affinity bind with the PD-L1 ligand, and the affinity of the prepared mutant PD-1 Fc fusion protein to bind to PD-L1 reached clinical anti-PD-L1 antibody levels. The investigators prepared BCMA CART cells which secretes the mutant PD-1Fc fusion protein, and the prepared CART cell culture supernatant can well block the binding of PD-L1 to PD-1. Preclinical studies have shown that BCMA CART cells secreting mutant PD-1Fc fusion protein have a superior killing effect on PD-L1 positive multiple myeloma tumor cells to BCMA CART cells which does not express PD-1 fusion protein. The trial was conducted to explore the safety and efficacy of BCMA-PD1-CART cells in Relapsed/Refractory Multiple Myeloma.

6. Conditions and Keywords

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

Multiple Myeloma

Keywords

BCMA, Myeloma, PD-1, Immunotherapy, Plasmocytoma, Chimeric antigen receptor T cell, Chimeric antigen receptor, B cell maturation antigen

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Model Description

This study was a single-center, open-label, single-arm, non-randomized clinical trial, which was divided into 3 groups by infusion dose level. Firstly, each dose group has 3 patients. The pretreatment regimen of cyclophosphamide (25mg/m2 for 3 consecutive days) and fludarabine (10mg/kg for 3 consecutive days) was given before CART cells were reinfused. CART cells were reinfused on the third day after the pretreatment. If no serious side effects emerges in the group, then the next group uses the subsequent higher dose. If serious side effects emerges in a single patient in any dose level, 3 more patients will be enrolled to the same dose level. After 9 or more patients, we select the safest dose and recruit more patients for CART test to explore its effectiveness.

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

multiple myeloma

Arm Type

Experimental

Arm Description

This study is to evaluate the efficacy and safety of BCMA-PD1-CART cells therapy for patients with Relapsed/Refractory Multiple Myeloma.

Intervention Type

Biological

Intervention Name(s)

BCMA-PD1-CART Cell

Intervention Description

Primary Outcome Measure Information:

Title

Incidence of Treatment-related Adverse Events

Description

Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0).

Time Frame

3 years

Secondary Outcome Measure Information:

Title

Overall Remission Rate(ORR) of BCMA-PD1-CART cells in Lymphoma

Description

ORR will be assessed from the first CAR-T cell infusion to death or last follow-up

Time Frame

3 years

Title

Overall survival(OS) of BCMA-PD1-CART cells in Lymphoma

Description

OS will be assessed from the first CAR-T cell infusion to death or last follow-up

Time Frame

3 years

Title

Progress-free survival(PFS) of BCMA-PD1-CART cells in Lymphoma

Description

PFS will be assessed from the first CAR-T cell infusion to death or last follow-up

Time Frame

3 years

Title

Rate of BCMA-PD1-CARTcells in peripheral blood cells

Description

In vivo (peripheral blood) rate of BCMA-PD1-CARTcells were determined by means of flow cytometry.

Time Frame

3 years

Title

Quantity of BCMA-PD1-CART cells copies in peripheral blood cells.

Description

In vivo (peripheral blood) quantity of BCMA-PD1-CART cells copies copies were determined by means of qPCR.

Time Frame

3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

14 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female, aged 14 to 80 years (including 14 and 80 years old). The diagnosis was Refractory/relapsed multiple myeloma.(Meeting 1 of the follow 3 items) A.Primary treatment patients with no effect after first and second line treatment. B.Patients who relapsed after complete remission and failed to respond to two kind of therapy. C.the predicted survival is more than three months. Flow cytometry or immunohistochemistry showed BCMA positive in tumor cells. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form. No serious concomitant disease and major organ function is not serious abnormal. No serious concomitant disease and major organ function is not serious abnormal. the test meets the following indicators: A.ALT/AST < 2.5 times the upper limit of normal (ULN) and total bilirubin≤34.2μmol/L. B.WBC≥2.5×109/L. C.PT/INR < 1.7 or PT was extended by less than 4 seconds. Exclusion Criteria: Women who are pregnant or breastfeeding. Transduced positive T lymphocytes < 5% or amplified against CD3/CD28 stimulation < 5 times. Active hepatitis B or hepatitis C, HIV/AIDS infection, any uncontrolled active infection. Patients who are using steroid drugs throughout the body currently. Patients who have received any gene therapy in the past. Patients who are allergy to immunotherapy and related drugs. Patients with heavy heart disease or poorly controlled high blood pressure. Patients who received chemotherapy or radiation 4 weeks before the study began. Patients who are participating in other clinical trials.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Quanshun Wang

Phone

15692538521

wqs63@sohu.com

First Name & Middle Initial & Last Name or Official Title & Degree

Wenshuai Zheng

Phone

15701572628

18766179210@163.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Quanshun Wang

Organizational Affiliation

Hainan Hospital of Chinese PLA General Hospital

Official's Role

Study Chair

First Name & Middle Initial & Last Name & Degree

Wenshuai Zheng

Organizational Affiliation

Hainan Hospital of Chinese PLA General Hospital

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Lixun Guan

Organizational Affiliation

Hainan Hospital of Chinese PLA General Hospital

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Lu Wang

Organizational Affiliation

Hainan Hospital of Chinese PLA General Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Yuanyuan Xu

Organizational Affiliation

Hainan Hospital of Chinese PLA General Hospital

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Zhenyang Guan

Organizational Affiliation

Hainan Hospital of Chinese PLA General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hainan Hospital of Chinese PLA General Hospital

City

Sanya

State/Province

Hainan

ZIP/Postal Code

572000

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Wenshuai Zheng

Phone

15701572628

18766179210@163.com

First Name & Middle Initial & Last Name & Degree

Quanshun Wang

First Name & Middle Initial & Last Name & Degree

Lixun Guan

First Name & Middle Initial & Last Name & Degree

Wenshuai Zheng

First Name & Middle Initial & Last Name & Degree

Zhenyang Gu

First Name & Middle Initial & Last Name & Degree

Lu Wang

First Name & Middle Initial & Last Name & Degree

Yuanyuan Xu

First Name & Middle Initial & Last Name & Degree

Yalei Hu

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Safety and Efficiency Study of BCMA-PD1-CART Cells in Relapsed/Refractory Multiple Myeloma

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