Clinical trial NCT04318327: BCMA-directed CAR-T Cell Therapy in Adult Patients With Multiple Myeloma
Official title: Phase I, Open Label, Study of B-cell Maturation Antigen (BCMA)-Directed CAR-T Cells in Adult Patients With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Multiple myeloma
B-cell maturation antigen
BCMA
anti-BCMA
BCMA-directed
chimeric antigen receptor
CAR-T
PHE885
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-03-23
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This was a first-in-human study to evaluate the feasibility, safety and preliminary antitumor efficacy of autologous T cells genetically engineered with a novel B-cell Maturation Antigen (BCMA)-specific chimeric antigen receptor (CAR) and manufactured with a new process. CAR-T cells were investigated as a single agent in multiple myeloma

Detailed description: This was a phase I, open label study to characterize the safety and tolerability of a novel B-cell Maturation Antigen (BCMA)-specific chimeric antigen receptor (CAR) manufactured with a new process. In the dose escalation part (Part A) of the study, the anti-BCMA CAR-T cell therapy was studied in adult multiple myeloma (MM) subjects who were relapsed and/or refractory. In the dose evaluation part (Part B) of the study, the anti-BCMA CAR-T cell therapy was studied in newly diagnosed adult subject with MM.

Eligibility criteria: Inclusion Criteria:

* Part A: Subjects with MM who are relapsed and/or refractory to at least 2 prior treatment regimens, including an IMiD (e.g. lenalidomide or pomalidomide), a proteasome inhibitor (e.g. bortezomib, carfilzomib), and an approved anti-CD38 antibody (e.g. daratumumab), if available, and have documented evidence of disease progression (IMWG criteria)
* Part A: ECOG performance status that is either 0 or 1 at screening
* Part B: Subjects with newly diagnosed multiple myeloma (NDMM) who have received a minimum of 4 and up to 6 cycles of standard induction therapy with VRd, D-VRd, or D-Rd, and have achieved a response of PR or better. One cycle of CyBorDex is allowed prior to induction.
* Part B: ECOG performance status that is either 0,1 or 2 at screening
* Measurable disease as defined by the protocol
* Adequate hematological values
* Must have a leukapheresis material of non-mobilized cells accepted for manufacturing

Exclusion Criteria:

* Prior administration of a genetically modified cellular product including prior BCMA CAR-T therapy. Patients who have received prior BCMA-directed bi-specific antibodies or antibody-drug conjugates (ADC) are not excluded.
* Autologous HSCT within 6 weeks prior to enrollment or any prior history of allogeneic hematopoietic stem cell transplant (HSCT)
* Chemotherapy or any concomitant anti-cancer therapies (other than protocol prescribed lymphodepletion (LD) chemotherapy) within 2 weeks prior to apheresis
* Treatment with small molecule targeted antineoplastics within 2 weeks of apheresis collection or 5 half-lives whichever is shorter
* Have received antibodies or immunotherapies (other than daratumumab) within 4 weeks prior to apheresis collection. Daratumumab within 3 weeks prior to apheresis collection.

Primary outcomes:
measure: Incidence of Dose limiting toxicities (DLT)
timeFrame: 28 days
measure: Nature of Dose limiting toxicities (DLT)
timeFrame: 28 days
measure: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 24 months
Secondary outcomes:
measure: Manufacture success rate (defined as number of subjects treated with planned target dose divided by total number of subjects treated)
timeFrame: 24 Months
measure: Overall Response Rate (ORR) in Part A
timeFrame: 24 months
measure: ORR in Part B
timeFrame: 24 months
measure: Response rate at 3 and 6 months in Part A
timeFrame: 3 months, 6 months
measure: Overall response rate at 3 and 6 months in Part B
timeFrame: 3 months, 6 months
measure: Overall Complete Response Rate (CRR) in Part A
timeFrame: 24 months
measure: Overall CRR in Part B
timeFrame: 24 months
measure: CRR at months 3 and 6 in Part A
timeFrame: 3 months, 6 months
measure: CRR at months 3 and 6 in Part B
timeFrame: 3 months, 6 months
measure: DOR (duration of response) in Part A
timeFrame: from disease response to disease progression, assessed up to approximately 24 months
measure: DOR in Part B
timeFrame: from disease response to disease progression, assessed up to approximately 24 months
measure: Cmax of BCMA CAR-T cells
timeFrame: 24 months
measure: Tmax of BCMA CAR-T cells
timeFrame: 24 months
measure: AUC of BCMA CAR-T cells
timeFrame: 24 months
measure: Clast of BCMA CAR-T cells
timeFrame: 24 months
measure: number of patients with pre-existing and treatment induced immunogenicity (cellular and humoral) of BCMA CAR-T cell therapy
timeFrame: 24 Months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Uni of Chi Medi Ctr Hema and Onco
state: Illinois
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Cente
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
Study officials:
References: