Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Plasmacytoma

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Immunomodulating Agents

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

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.

BCMA-PD1-CART Cell

Quanshun Wang

Wenshuai Zheng

Lixun Guan

Zhenyang Gu

Lu Wang

Yuanyuan Xu

Yalei Hu

Zhenyang Guan

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.

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.

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

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).

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

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

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

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

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

Chinese PLA General Hospital

Chief of Hematology Department of Hainan Hospital of PLA General Hospital; Vice Chief of Hematology Department of PLA General Hospital

Antibodies

Antibodies, Monoclonal

Immunoglobulins

ACTR087

B-cell maturation antigen (BCMA)-directed antibody

SEA-BCMA

Jessica Sachs, MD

This is a phase 1, multi-center, single-arm, open-label study evaluating the safety, tolerability, and anti-myeloma activity of ACTR087 (an autologous T cell product) in combination with SEA-BCMA (a monoclonal antibody) in subjects with relapsed or refractory Multiple Myeloma.

Study of ACTR087 in Combination With SEA-BCMA in Subjects With Relapsed or Refractory Multiple Myeloma

A Phase 1 Study of ACTR087, an Autologous T Cell Product, in Combination With SEA-BCMA, a Monoclonal Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma

Composite outcome measure assessed by committee review of dose limiting toxicities (DLTs), incidence and severity of AEs and clinically significant abnormalities of laboratory values

Review of DLTs, Maximum tolerated contour (MTC), incidence and severity of AEs and clinically significant abnormalities of laboratory values

Review of all TEAEs, including incidence and severity of AEs, DLTs and clinically significant abnormalities of laboratory values

Levels of inflammatory markers, cytokines/chemokines

Seagen Inc.

Cogent Biosciences, Inc.

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Autologous CD8+ T-cells transiently expressing an anti-BCMA chimeric antigen receptor

autologous CD8+ T-cells transiently expressing an anti-BCMA chimeric antigen receptor

Descartes-08

Metin Kurtoglu, MD, PhD

This Phase I/II study will test the safety and anti-myeloma activity of ascending doses of Descartes-08 (autologous CD8+ T-cells expressing an anti-BCMA chimeric antigen receptor) in eligible patients with active multiple myeloma.

Autologous CD8+ T-cells Expressing an Anti-BCMA CAR in Patients With Myeloma

Combined Phase I-Phase II Study of Autologous CD8+ T-cells Transiently Expressing a Chimeric Antigen Receptor Directed to B-Cell Maturation Antigen in Patients With Multiple Myeloma

Incidence (number) of Treatment-Emergent Adverse Events \[Safety and Tolerability\]. Descriptive statistics by incidence rate, body system classification, severity, and causality \[per protocol definitions\]

Cartesian Therapeutics

Descartes-11

This Phase I/2 study will test the safety and anti-myeloma activity of ascending doses of Descartes-11 (autologous CD8+ T-cells expressing an anti-BCMA chimeric antigen receptor) in eligible patients with active multiple myeloma.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Safety and Efficiency Study of BCMA-PD1-CART Cells in Relapsed/Refractory Multiple Myeloma	NCT04162119	Multiple Myelom...	BCMA-PD1-CART C...	14 Years - 80 Years	Chinese PLA General Hospital
Safety and Efficiency Study of BCMA-PD1-CART Cells in Relapsed/Refractory Multiple Myeloma	NCT04162119	Multiple Myelom...	BCMA-PD1-CART C...	14 Years - 80 Years	Chinese PLA General Hospital
Study of ACTR087 in Combination With SEA-BCMA in Subjects With Relapsed or Refractory Multiple Myeloma	NCT03266692	Multiple Myelom... Multiple Myelom... Refractory Mult...	ACTR087 SEA-BCMA	18 Years - 80 Years	Cogent Biosciences, Inc.
Autologous CD8+ T-cells Expressing an Anti-BCMA CAR in Patients With Myeloma	NCT03448978	Multiple Myelom...	Descartes-08 Fludarabine Cyclophosphamid...	18 Years -	Cartesian Therapeutics
Descartes-11 in Multiple Myeloma	NCT03994705	Multiple Myelom...	Descartes-11 Fludarabine Cyclophosphamid...	18 Years -	Cartesian Therapeutics

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