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

Phase 2

• Conditions: Multiple Myeloma
• Interventions: Biological: BCMA-PD1-CART Cell

• Registration Number: NCT04162119
• Lead Sponsor: Chinese PLA General Hospital

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.

Study Timeline

• Study Start: 2019-07-07
• Status Verified: 2019-11
• Study First Submitted: 2019-11-11
• Study First Submitted QC: 2019-11-11
• Study First Posted: 2019-11-14
• Last Update Submitted: 2019-11-14
• Last Update Posted: 2019-11-18
• Primary Completion: 2021-10-10
• Study Completion: 2022-10-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Male or female, aged 14 to 80 years (including 14 and 80 years old).

2. 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.

3. Flow cytometry or immunohistochemistry showed BCMA positive in tumor cells.

4. Patient or his or her legal guardian voluntarily participates in and signs an informed consent form.

5. No serious concomitant disease and major organ function is not serious abnormal.

6. No serious concomitant disease and major organ function is not serious abnormal.

7. 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.

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Exclusion Criteria

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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-related Adverse Events	3 years	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

Name	Time	Method
Overall Remission Rate(ORR) of BCMA-PD1-CART cells in Lymphoma	3 years	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	3 years	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	3 years	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	3 years	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.	3 years	In vivo (peripheral blood) quantity of BCMA-PD1-CART cells copies copies were determined by means of qPCR.

Trial Locations

Locations (1)

Hainan Hospital of Chinese PLA General Hospital; 🇨🇳 Sanya, Hainan, China