Clinical trial NCT03464916: Study to Evaluate the Safety and Efficacy of Anti-CD38 CAR-T in Relapsed or Refractory Multiple Myeloma Patients
Official title: A Phase 1, Open-Label, Dose-Escalation, Pharmacokinetic, and Pharmacodynamic Study of the Safety and Efficacy of CAR2 Anti-CD38 A2 CAR-T Cells in Patients With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsed or Refractory Multiple Myeloma
Keywords: CAR2 Anti-CD38 A2 CAR-T Cells
Lead sponsor: Sorrento Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2018-03-14
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: To determine DLT and MTD, the design uses a 3+3 rule-based design. Dose escalation is permitted between successive cohorts based upon a specified algorithm, using discrete dosage steps.
Primary purpose: TREATMENT

Brief summary: The study is an open-label Phase 1 single dose-escalation safety study of CAR2 Anti-CD38 A2 CAR-T Cells in patients with Relapsed or Refractory Multiple Myeloma, who meet all other eligibility criteria.

Detailed description: All subjects who received investigational CAR-T therapy will be included in the analyses and summaries of safety, efficacy, pharmacokinetic, and pharmacodynamic assessments.

Eligibility criteria: Inclusion Criteria:

* The patient must either have relapsed refractory multiple myeloma (RRMM) after receiving prior lines of anti-myeloma treatments that included at least lenalidomide (Revlimid®), pomalidomide (Pomalyst®), bortezomib (Velcade®), carfilzomib (Kyprolis®), and daratumumab (Darzalex®) (refractory MM is defined as the development of disease progression during therapy with an anti-myeloma regimen or within 60 days of the last dose of an anti-myeloma regimen or the achievement of less than a partial response (PR) after greater than or equal to 2 cycles; for relapsing patients the duration from the last dose of the last prior treatment regimen to relapse must be less than or equal to 12 months); OR have multiple myeloma that is refractory to or has relapsed within 1 year of receiving high-dose therapy \[HDT\]/autologous stem cell transplantation \[ASCT\] in first- or second-line (refractory is defined as the achievement of less than a PR at the Day 90 to 100 post-ASCT response assessment)
* Must have measurable disease as defined by the following: Serum M-protein greater than or equal to 1 g/dL; OR Urine M-protein greater than or equal to 200 mg/24 hours; OR Serum free light chain (FLC) assay; involved FLC level greater than or equal to 10 mg/dL provided the serum FLC ratio is abnormal; OR greater than or equal to 30% clonal plasma cells in the bone marrow aspirate or biopsy sample
* Must have a life expectancy of at least 12 weeks
* Subjects should be willing and able to comply with the study schedule and protocols
* Females of childbearing potential must have 2 negative pregnancy tests, agree to ongoing pregnancy testing during the study, and sexually active female and male subjects must be willing to use an effective method to avoid pregnancies.

Exclusion Criteria:

* Subjects who received anticancer therapy or investigational drug within 28 days of first dose
* Subjects who received any approved anticancer chemotherapy within 21 days of first dose (exception cyclophosphamide as NMA conditioning)
* Subjects with unresolved toxicity greater than Grade 2 from previous therapies
* Have myeloma involvement of central nervous system (CNS) or a history of brain metastasis or spinal cord compression
* Subjects with an ECOG performance status greater than or equal to 3
* Has received allogenic hematopoietic stem cell transplantation (HSCT) within 6 months, have active graft-versus-host disease (GVHD) following transplant, or receiving immunosuppressive therapy following a transplant
* Has received any CAR cell line therapies
* Has any clinically significant low baseline lab results for hemoglobin, platelet counts, and neutrophil counts, at screening unless resulting from underlying RRMM.
* Has any clinically significant elevated baseline lab results for serum creatinine, AST, and total bilirubin (except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome) at screening regardless of causality.
* Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of chronic hepatitis B or C.
* Female subjects who are pregnant or breastfeeding
* Active bacterial, viral or fungal infections
* Has active plasma cell leukemia
* Has medical condition, abnormality, or psychiatric illness that would prevent study participation
* Left ventricular ejection fraction (LVEF) less than 40%

Primary outcomes:
measure: Determine the MTD
timeFrame: 28 days
Secondary outcomes:
measure: Determine the CAR2 Anti-CD38 A2 CAR-T cell blood concentrations (Pharmacokinetic [PK] Profile) to evaluate the Cmax
timeFrame: 28 days
measure: Determine the CAR2 Anti-CD38 A2 CAR-T cell blood concentrations (Pharmacokinetic [PK] Profile) to evaluate the AUC
timeFrame: 28 days
measure: Evaluate the safety of Anti-CD38 A2 CAR-T cells in Patients with RRMM by incidence of treatment-emergent adverse events
timeFrame: 6 months
measure: Assess preliminary efficacy by response rate in accordance with the modified International Myeloma Working Group (IMWG) criteria
timeFrame: 6 months
measure: Assess preliminary efficacy by depth of response in accordance with the modified International Myeloma Working Group (IMWG) criteria.
timeFrame: 6 months
measure: Assess preliminary efficacy by duration of response in accordance with the modified International Myeloma Working Group (IMWG) criteria.
timeFrame: 6 months
measure: Assess preliminary efficacy by progression-free survival.
timeFrame: 6 months
measure: Assess preliminary efficacy by overall survival.
timeFrame: 6 months
measure: The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of treatment-emergent events.
timeFrame: 6 months
measure: The determination of the recommended phase 2 dose will be based on an evaluation of overall response rate.
timeFrame: 6 months
measure: The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of depth of response.
timeFrame: 6 months
measure: The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of duration of response.
timeFrame: 6 months
measure: The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of progression-free survival.
timeFrame: 6 months
measure: The determination of the recommended phase 2 dose (RP2D) will be based on an evaluation of overall survival.
timeFrame: 6 months
Other outcomes:
measure: An assessment of pharmacodynamics will be based on determining if there is an association of the achievement of at least a partial response with the level of Cmax of circulating CAR-T cells.
timeFrame: 6 months
measure: An assessment of pharmacodynamics will be based on determining if there is an association of the achievement of at least a partial response with the AUC of circulating CAR-T cells.
timeFrame: 6 months
measure: An assessment of pharmacodynamics will be based on determining if there is an association of the incidence of at least Grade 3 cytokine release syndrome (CRS) adverse events with the level of Cmax of circulating CAR-T cells.
timeFrame: 6 months
measure: An assessment of pharmacodynamics will be based on determining if there is an association of the incidence of at least Grade 3 CRS with the AUC of circulating CAR-T cells.
timeFrame: 6 months
measure: An assessment of pharmacodynamics will be based on determining if there is an association of the incidence of at least Grade 2 neurotoxicity adverse events with the level of Cmax of circulating CAR-T cells.
timeFrame: 6 months
measure: An assessment of pharmacodynamics will be based on determining if there is an association of the incidence of at least Grade 2 neurotoxicity adverse events with the AUC of circulating CAR-T cells.
timeFrame: 6 months
Locations:
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic Minnesota
state: Minnesota
city: New York
country: United States
facility: Icahn School of Medicine
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania, Abramson Cancer Center
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Edward Stadtmauer, MD
role: PRINCIPAL_INVESTIGATOR
References: