Up-front CART-BCMA With or Without huCART19 in High-risk Multiple Myeloma

Summary

This is an open-label, phase 1 study to assess the safety, pharmacodynamics, and anti-myeloma effects of autologous T cells expressing BCMA (B-cell maturation antigen)-specific chimeric antigen receptors with tandem TCRζ and 4-1BB (TCRζ /4-1BB) costimulatory domains (referred to as "CART-BCMA"), with or without huCART19 (also known as CTL119), in patients responding to first- or second-line therapy for high-risk multiple myeloma, and in relapsed/refractory multiple myeloma patients responding to salvage therapy.

Conditions

• Multiple Myeloma

Interventions

BIOLOGICAL

BCMA CART + huCART19

The target dose for CART-BCMA and huCART19 will be 5x10\^8 CAR-expressing cell for each product. Split dose infusions will consist of a 10% dose (of one or both products) on the first infusion day, 30% dose (of one or both products) on the second infusion day, or 60% dose (of one or both products) on the third infusion day. Infusion days may be spread over 7 calendar days due to scheduling constraints or to allow observation of suspected early cytokine release syndrome or other toxicity. Infusions will begin 3 days (+/- 1 day) after completion of lymphodepleting chemotherapy with cyclophosphamide + fludarabine.

BIOLOGICAL

CART BCMA or CART BCMA + huCART19

The target dose for CART-BCMA and huCART19 will be 5x10\^8 CAR-expressing cell for each product. Cohort 1 refers to the group of subjects assigned to receive CART-BCMA alone; Cohort 2 refers to the group of subjects assigned to receive CART-BCMA + huCART19. Split dose infusions will consist of a 10% dose (of one or both products) on the first infusion day, 30% dose (of one or both products) on the second infusion day, or 60% dose (of one or both products) on the third infusion day. Infusion days may be spread over 7 calendar days due to scheduling constraints or to allow observation of suspected early cytokine release syndrome or other toxicity. Infusions will begin 3 days (+/- 1 day) after completion of lymphodepleting chemotherapy with cyclophosphamide + fludarabine.

BIOLOGICAL

Single-dose infusion of CART BCMA or CART BCMA + huCART19

The target dose for CART-BCMA and huCART19 will be 5x10\^8 CAR-expressing cell for each product. Cohort 1 refers to the group of subjects assigned to receive single dose infusions of CART-BCMA alone; Cohort 2 refers to the group of subjects assigned to receive single dose infusions of CART-BCMA + huCART19. Infusions will begin 3 days (+/- 1 day) after completion of lymphodepleting chemotherapy with cyclophosphamide + fludarabine.

BIOLOGICAL

BCMA CART + huCART19

The target dose for CART-BCMA and huCART19 will be 5x10\^8 CAR-expressing cell for each product. Split dose infusions will consist of a 10% dose (of one or both products) on the first infusion day, 30% dose (of one or both products) on the second infusion day, or 60% dose (of one or both products) on the third infusion day. Infusion days may be spread over 7 calendar days due to scheduling constraints or to allow observation of suspected early cytokine release syndrome or other toxicity. Infusions will begin 3 days (+/- 1 day) after completion of lymphodepleting chemotherapy with cyclophosphamide + fludarabine.

Sponsors & Collaborators

• Novartis

  collaborator INDUSTRY

• National Institutes of Health (NIH)

  collaborator NIH

• University of Pennsylvania

  lead OTHER

Principal Investigators

• Alfred Garfall, MD · University of Pennsylvania

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-05-09

Primary Completion

2036-03-31

Completion

2036-03-31

FDA Drug

Yes

Countries

• United States

Study Locations