BCMA-directed CAR-T Cell Therapy in Adult Patients With Relapsed and/or Refractory Multiple Myeloma
Study Details
Study Description
Brief 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 relapsed/refractory multiple myeloma
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PHE885 Patients will receive PHE885 |
Biological: PHE885
Infusion
|
Outcome Measures
Primary Outcome Measures
- Incidence of Dose limiting toxicities (DLT) [24 months]
Incidence of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration
- Nature of Dose limiting toxicities (DLT) [24 months]
Nature of Dose Limiting Toxicities (DLTs) during the first 28 days after anti-BCMA CAR-T cell administration
- Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [24 months]
Secondary Outcome Measures
- Manufacture success rate (defined as number of subjects treated with planned target dose divided by total number of subjects treated) [24 Months]
evaluate the feasibility of the manufacturing process
- ORR (overall response rate): Proportion of subjects with the best overall response (BOR) [month 3, month 6]
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)
- CRR (complete response rate) [3 months]
Proportion of subjects with the BOR of sCR+CR at Month 3, as determined by local investigator using the IMWG Criteria.
- DOR (duration of response) [12 months]
as assessed by local investigator: the time from achievement of sCR+CR+VGPR+PR to relapse or death due to MM (multiple myeloma)
- Cmax of BCMA CAR-T cells [24 months]
through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
- Tmax of BCMA CAR-T cells [24 months]
through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
- AUC of BCMA CAR-T cells [24 months]
through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
- Clast of BCMA CAR-T cells [24 months]
through qPCR-detected transgene of CART concentrations over time in peripheral blood and bone marrow
- number of patients with pre-existing and treatment induced immunogenicity (cellular and humoral) of BCMA CAR-T cell therapy [24 Months]
Eligibility Criteria
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)
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Measurable disease as defined by the protocol
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ECOG performance status that is either 0 or 1 at screening
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Adequate hematological values
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Must have a leukapheresis material of non-mobilized cells accepted for manufacturing
Exclusion Criteria:
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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.
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Autologous HSCT within 6 weeks prior to enrollment or any prior history of allogeneic hematopoietic stem cell transplant (HSCT)
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Chemotherapy or any concomitant anti-cancer therapies (other than protocol prescribed lymphodepletion (LD) chemotherapy) within 2 weeks prior to apheresis
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Treatment with small molecule targeted antineoplastics within 2 weeks of apheresis collection or 5 half-lives whichever is shorter
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Have received antibodies or immunotherapies (other than daratumumab) within 4 weeks prior to apheresis collection. Daratumumab within 3 weeks prior to apheresis collection.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Chicago Medical Center Hematology and Oncology | Chicago | Illinois | United States | 60637 |
| 2 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 3 | Beth Israel Deaconess Medical Cente KS121 | Boston | Massachusetts | United States | 02215 |
| 4 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 5 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CADPT07A12101