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

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.

Study Overview

• Status: Unknown
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: BCMA-PD1-CART Cell

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Quanshun Wang; Phone Number: 15692538521; Email: wqs63@sohu.com
• Study Contact Backup: Name: Wenshuai Zheng; Phone Number: 15701572628; Email: 18766179210@163.com

Study Locations

• China
  • Hainan
    • Sanya, Hainan, China, 572000
      • Recruiting
      • Hainan hospital of Chinese PLA General Hospital
      • Contact: Wenshuai Zheng; Phone Number: 15701572628; Email: 18766179210@163.com
      • Principal Investigator: Quanshun Wang
      • Principal Investigator: Lixun Guan
      • Principal Investigator: Wenshuai Zheng
      • Principal Investigator: Zhenyang Gu
      • Principal Investigator: Lu Wang
      • Principal Investigator: Yuanyuan Xu
      • Principal Investigator: Yalei Hu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 80 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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.

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

Biological: BCMA-PD1-CART Cell; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	3 years
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	3 years
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	3 years
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.	3 years
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.	3 years

Collaborators and Investigators

• Sponsor: Chinese PLA General Hospital
• Investigators: Study Chair: Quanshun Wang, Hainan hospital of Chinese PLA General Hospital; Study Director: Wenshuai Zheng, Hainan hospital of Chinese PLA General Hospital; Study Director: Lixun Guan, Hainan hospital of Chinese PLA General Hospital; Principal Investigator: Lu Wang, Hainan hospital of Chinese PLA General Hospital; Principal Investigator: Yuanyuan Xu, Hainan hospital of Chinese PLA General Hospital; Principal Investigator: Zhenyang Guan, Hainan hospital of Chinese PLA General Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 7, 2019
• Primary Completion (ANTICIPATED): October 10, 2021
• Study Completion (ANTICIPATED): October 10, 2022

Study Registration Dates

• First Submitted: November 11, 2019
• First Submitted That Met QC Criteria: November 11, 2019
• First Posted (ACTUAL): November 14, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 18, 2019
• Last Update Submitted That Met QC Criteria: November 14, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Immunotherapy; PD-1; Myeloma; Chimeric antigen receptor; BCMA; B cell maturation antigen; Plasmocytoma; 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
• Other Study ID Numbers: HNYY-XYK-01

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