BCMA-directed CAR-T Cell Therapy in Adult Patients With Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

Phase I, Open Label, Study of B-cell Maturation Antigen (BCMA)-Directed CAR-T Cells in Adult Patients With Multiple Myeloma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04318327
• Other study ID #: CADPT07A12101
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: July 23, 2020
• Est. completion date: February 19, 2026

Study information

• Verified date: January 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is 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 will be investigated as a single agent in multiple myeloma

Description:

This is 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 will be studied in adult multiple myeloma (MM) subjects who are relapsed and/or refractory. In the dose evaluation part (Part B) of the study, the anti-BCMA CAR-T cell therapy will be studied in newly diagnosed adult subject with MM.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 96
• Est. completion date: February 19, 2026
• Est. primary completion date: February 19, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• PHE885
Infusion

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Camperdown
Australia	Novartis Investigative Site	Prahran	Victoria
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Ramat Gan
Israel	Novartis Investigative Site	Tel Aviv
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
United States	Beth Israel Deaconess Medical Cente KS121	Boston	Massachusetts
United States	Dana Farber Cancer Institute Main Centre	Boston	Massachusetts
United States	University of Chicago Medical Center Hematology and Oncology	Chicago	Illinois
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Kansas Cancer Center .	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Israel,  Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Dose limiting toxicities (DLT)	Incidence of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration	28 days
Primary	Nature of Dose limiting toxicities (DLT)	Nature of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration	28 days
Primary	Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)		24 months
Secondary	Manufacture success rate (defined as number of subjects treated with planned target dose divided by total number of subjects treated)	evaluate the feasibility of the manufacturing process	24 Months
Secondary	Overall Response Rate (ORR) in Part A	Proportion of subjects with the best overall response (BOR) of PR (partial response) or better, as determined by local investigator using the IMWG Criteria	24 months
Secondary	ORR in Part B	Proportion of subjects with VGPR (very good partial response) or PR to induction therapy who achieve the BOR of PR or better, as determined by local investigator using the IMWG Criteria	24 months
Secondary	Response rate at 3 and 6 months in Part A	Proportion of subjects with the overall response of PR or better at months 3 and 6 after infusion respectively, as determined by local investigator using the IMWG Criteria	3 months, 6 months
Secondary	Overall response rate at 3 and 6 months in Part B	Proportion of subjects with VGPR or PR to induction therapy who achieve the overall response of PR or better at months 3 and 6 after infusion respectively, as determined by local investigator using the IMWG Criteria	3 months, 6 months
Secondary	Overall Complete Response Rate (CRR) in Part A	Proportion of subjects with the BOR of CR or better, as determined by local investigator using the IMWG Criteria	24 months
Secondary	Overall CRR in Part B	Proportion of subjects with a response of VGPR or PR to induction therapy with the BOR of CR or better, as determined by local investigator using the IMWG Criteria	24 months
Secondary	CRR at months 3 and 6 in Part A	Proportion of subjects with the overall response of CR or better at months 3 and 6 respectively, as determined by local investigator using the IMWG Criteria	3 months, 6 months
Secondary	CRR at months 3 and 6 in Part B	Proportion of subjects with a response of VGPR or PR to induction therapy with the overall response of CR or better at months 3 and 6 after infusion, respectively, as determined by local investigator using the IMWG Criteria	3 months, 6 months
Secondary	DOR (duration of response) in Part A	DOR as assessed by local investigator: the time from achievement of PR or better to relapse or death due to MM (multiple myeloma)	from disease response to disease progression, assessed up to approximately 24 months
Secondary	DOR in Part B	DOR as assessed by local investigator: The time from the first documented disease response after infusion of CR or better to the date of the first documented progression as assessed by IMGW or death due to MM, for subjects with a response of VGPR or PR to induction therapy, and; The time from the first documented disease response after infusion of PR or better to the date of the first documented progression as assessed by IMGW or death due to MM, for subjects with a response of VGPR or PR to induction therapy	from disease response to disease progression, assessed up to approximately 24 months
Secondary	Cmax of BCMA CAR-T cells	through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow	24 months
Secondary	Tmax of BCMA CAR-T cells	through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow	24 months
Secondary	AUC of BCMA CAR-T cells	through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow	24 months
Secondary	Clast of BCMA CAR-T cells	through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow	24 months
Secondary	number of patients with pre-existing and treatment induced immunogenicity (cellular and humoral) of BCMA CAR-T cell therapy		24 Months