Description:
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 relapsed/refractory multiple myeloma
Title
- Brief Title: BCMA-directed CAR-T Cell Therapy in Adult Patients With Relapsed and/or Refractory Multiple Myeloma
- Official Title: Phase I, Open Label, Study of B-cell Maturation Antigen (BCMA)-Directed CAR-T Cells in Adult Patients With Relapsed and/or Refractory Multiple Myeloma
Clinical Trial IDs
- ORG STUDY ID:
CADPT07A12101
- NCT ID:
NCT04318327
Conditions
Interventions
Drug | Synonyms | Arms |
---|
PHE885 | | PHE885 |
Purpose
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 relapsed/refractory multiple myeloma
Trial Arms
Name | Type | Description | Interventions |
---|
PHE885 | Experimental | Patients will receive PHE885 | |
Eligibility Criteria
Inclusion Criteria:
- 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)
- Measurable disease as defined by the protocol
- ECOG performance status that is either 0 or 1 at screening
- 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of Dose limiting toxicities (DLT) |
Time Frame: | 24 months |
Safety Issue: | |
Description: | Incidence of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration |
Secondary Outcome Measures
Measure: | Manufacture success rate (defined as number of subjects treated with planned target dose divided by total number of subjects treated) |
Time Frame: | 24 Months |
Safety Issue: | |
Description: | evaluate the feasibility of the manufacturing process |
Measure: | ORR (overall response rate): Proportion of subjects with the best overall response (BOR) |
Time Frame: | month 3, month 6 |
Safety Issue: | |
Description: | BOR (best overall response) of sCR (stringent complete response) +CR (complete response) +VGPR (very good partial response)+PR (partial response) at Months 3 and 6, as determined by local investigator using the IMWG (International Myeloma Working Group) Criteria (Kumar et al, 2016) |
Measure: | CRR (complete response rate) |
Time Frame: | 3 months |
Safety Issue: | |
Description: | Proportion of subjects with the BOR of sCR+CR at Month 3, as determined by local investigator using the IMWG Criteria. |
Measure: | DOR (duration of response) |
Time Frame: | 12 months |
Safety Issue: | |
Description: | as assessed by local investigator: the time from achievement of sCR+CR+VGPR+PR to relapse or death due to MM (multiple myeloma) |
Measure: | Cmax of BCMA CAR-T cells |
Time Frame: | 24 months |
Safety Issue: | |
Description: | through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow |
Measure: | Tmax of BCMA CAR-T cells |
Time Frame: | 24 months |
Safety Issue: | |
Description: | through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow |
Measure: | AUC of BCMA CAR-T cells |
Time Frame: | 24 months |
Safety Issue: | |
Description: | through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow |
Measure: | Clast of BCMA CAR-T cells |
Time Frame: | 24 months |
Safety Issue: | |
Description: | through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow |
Measure: | number of patients with pre-existing and treatment induced immunogenicity (cellular and humoral) of BCMA CAR-T cell therapy |
Time Frame: | 24 Months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- Multiple myeloma, B-cell maturation antigen, BCMA, anti-BCMA, BCMA-directed, chimeric antigen receptor, CAR-T, PHE885
Last Updated
July 27, 2021