Conditions: Recurrent Plasma Cell Myeloma Refractory Plasma Cell Myeloma
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 28
Healthy volunteers: no

Brief summary:
This phase I trial studies the side effects and best dose of BCMA CAR-T cells in treating patients with BCMA positive multiple myeloma that has come back or does not respond to treatment. T cells are a type of white blood cell and a major component of the immune system. T-cells that have been genetically modified in the laboratory express BCMA and may kill cancer cells with the protein BCMA on their surface. Giving chemotherapy before BCMA CAR-T cells may reduce the amount of disease and to cause a low lymphocyte (white blood cell) count in the blood, which may help the infused BCMA CAR-T cells survive and expand.

Detailed description:
PRIMARY OBJECTIVE:

I. To evaluate the safety of adoptive therapy with ex vivo expanded autologous CD8+ plus CD4+ T cells transduced to express a human B cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) for patients with relapsed or treatment refractory multiple myeloma.

SECONDARY OBJECTIVES:

I. To determine the duration of in vivo persistence and the phenotype of long lived CAR-T cells.

II. To determine the degree to which adoptively transferred T cells traffic to multiple myeloma (MM) cells in the bone marrow (BM) and function in vivo.

III. To estimate the antitumor activity of adoptively transferred BCMA-specific CAR-expressing T lymphocytes (BCMA CAR-T cells).

OUTLINE: This is a dose-escalation study of BCMA-specific CAR-expressing T lymphocytes.

Patients undergo leukapheresis to obtain their immune cells, from which CAR-T cells are produced. A few weeks later, patients then receive cyclophosphamide and fludarabine on days -4 to -2. Beginning 36-96 hours after chemotherapy, patients receive BCMA-specific CAR-expressing T lymphocytes intravenously (IV) over 20-30 minutes on day 0. Patients may receive a second dose of BCMA-specific CAR-expressing T lymphocytes IV with or without additional cytoreductive chemotherapy at the discretion of the principal investigator or their designee (sub-investigator).

After completion of study treatment, patients are followed up at 60, 90, 120, 180, and 365 days and then annually up to 15 years.

Arms:
arm 1: Patients undergo leukapheresis. Patients then receive cyclophosphamide and fludarabine on days -4 to -2. Beginning to 36-96 days after chemotherapy, patients receive BCMA-specific CAR-expressing T lymphocytes IV over 20-30 minutes on day 0. Patients may receive a second dose of BCMA-specific CAR-expressing T lymphocytes IV with or without additional cytoreductive chemotherapy at the discretion of the principal investigator or their designee (sub-investigator).

Arm 1 contains patients treated as dose level 1 (50 x 10\^6 EGFRt cells) arm 2: Patients undergo leukapheresis. Patients then receive cyclophosphamide and fludarabine on days -4 to -2. Beginning to 36-96 days after chemotherapy, patients receive BCMA-specific CAR-expressing T lymphocytes IV over 20-30 minutes on day 0. Patients may receive a second dose of BCMA-specific CAR-expressing T lymphocytes IV with or without additional cytoreductive chemotherapy at the discretion of the principal investigator or their designee (sub-investigator).

Arm 2 contains patients treated as dose level 2 (150 x 10\^6 EGFRt cells) arm 3: Patients undergo leukapheresis. Patients then receive cyclophosphamide and fludarabine on days -4 to -2. Beginning to 36-96 days after chemotherapy, patients receive BCMA-specific CAR-expressing T lymphocytes IV over 20-30 minutes on day 0. Patients may receive a second dose of BCMA-specific CAR-expressing T lymphocytes IV with or without additional cytoreductive chemotherapy at the discretion of the principal investigator or their designee (sub-investigator).

Arm 3 contains patients treated as dose level 3 (300 x 10\^6 EGFRt cells) arm 4: Patients undergo leukapheresis. Patients then receive cyclophosphamide and fludarabine on days -4 to -2. Beginning to 36-96 days after chemotherapy, patients receive BCMA-specific CAR-expressing T lymphocytes IV over 20-30 minutes on day 0. Patients may receive a second dose of BCMA-specific CAR-expressing T lymphocytes IV with or without additional cytoreductive chemotherapy at the discretion of the principal investigator or their designee (sub-investigator).

Arm 4 contains patients treated as dose level 4 (450 x 10\^6 EGFRt cells)

Interventions: intervention 1: Autologous Anti-BCMA-CAR-expressing CD4+/CD8+ T-lymphocytes FCARH143 intervention 2: Cyclophosphamide intervention 3: Fludarabine intervention 4: Leukapheresis
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: Undergo leukapheresis

Protocol document:
Prot_SAP_000.pdf: 
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IRO received 09/15/20
FHCRC IRB Approval  
10/07/2020 
Document Released Date
9762
IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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Printed on 4/7/2022


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Printed on 4/7/2022
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Printed on 4/7/2022
Printed on 4/7/2022


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Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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9762
IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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9762
IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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9762
IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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9762
IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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Printed on 4/7/2022


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Printed on 4/7/2022
Printed on 4/7/2022


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Printed on 4/7/2022
Printed on 4/7/2022


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Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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Dose level
BCMA CAR T Cell Dose
0
   25 x 106 EGFRt+ cells
1 (Starting dose level)
50 x 106 EGFRt+ cells
2
150 x 106 EGFRt+cells
3
300 x 106 EGFRt+ cells
4
450 x 106 EGFRt+ cells
5
800 x 106 EGFRt+ cells
Table 5.1 Dose levels to be used during dose escalation
[EGFRt is co-expressed in the CAR vector and serves as a transduc-
tion marker to determine the number of CAR-T cells in the cell prod-
uct to define cell dose.]
9762
IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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Printed on 4/7/2022
Printed on 4/7/2022


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Printed on 4/7/2022


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Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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Printed on 4/7/2022


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Printed on 4/7/2022
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Printed on 4/7/2022


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Printed on 4/7/2022
Printed on 4/7/2022


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9762
IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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Printed on 4/7/2022
Printed on 4/7/2022


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Printed on 4/7/2022
Printed on 4/7/2022


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Printed on 4/7/2022
Printed on 4/7/2022


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Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022


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IRB Approved 
Document Release Date: 10/07/2020
Printed on 4/7/2022
Printed on 4/7/2022