Clinical trial NCT04720313: NXC-201 (formerly HBI0101) Multiple Myeloma
Official title: A Phase 1 Dose Escalation and Safety Study of NXC-201 (formerly HBI0101) CART in BCMA-Expressing Multiple Myeloma Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Dose Escalation and Safety
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
Collaborators: name: Nexcella Inc.
First posted: 2021-01-22
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Multiple Myeloma and AL amyloidosis Patients
Primary purpose: TREATMENT

Brief summary: It is a phase one study with dose escalation and safety CART in BCMA- Expressing Multiple Myeloma and AL amyloidosis Patients

Detailed description: The intention with NXC-201 (formerly HBI0101) CART is to follow the chimeric antigen receptor T-cells (CART) approach, as for approved products, but target the B cell maturation antigen (BCMA) rather than the CD19 antigen targeted by KYMRIAHTM (tisagenlecleucel) and YESCARTATM (axicabtagene ciloleucel).

Importantly, successful results from at least three clinical trials of a BCMA targeted CAR T therapy were published (Zhao 2018, Brundo 2018, Raje 2019), with excellent results obtained for relapsed or refractory multiple myeloma (MM) patients, that validate the approach.

Eligibility criteria: Inclusion Criteria:

* ≥18 years of age

  * Voluntarily signed informed consent form (ICF)
  * Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
  * Diagnosis of MM with relapsed or refractory disease and have had at least 3 different prior lines of therapy including proteasome inhibitor, immunomodulatory therapy and at least one antibody therapy.
  * Subjects must have measurable disease, including at least one of the criteria below:

    * Serum M-protein greater or equal to 0.5 g/dL
    * Urine M-protein greater or equal to 200 mg/24 h
    * Serum free light chain (FLC) assay: involved FLC level greater or equal to 5 mg/dL (50 mg/L) provided serum FLC ratio is abnormal
    * A biopsy-proven evaluable plasmacytoma
    * Bone marrow plasma cells \> 20% of total bone marrow cells
    * Non secretory patient will be allowed provided they have measurable disease by PET-CT or bone marrow aspiration, as designated.
  * Women of child-bearing potential (WCBP), must have a negative serum pregnancy test prior to treatment. All sexually active WCBP and all sexually active male subjects must agree to use effective methods of birth control throughout the study
  * Recovery to ≤Grade 2 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 3 neuropathy
  * Ability and willingness to adhere to the study visit schedule and all protocol requirements

Primary outcomes:
measure: Determination of MTD
timeFrame: 21 days
Secondary outcomes:
measure: The overall survival
timeFrame: 2 years
measure: The progression-free survival
timeFrame: 2 years
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
Study officials:
affiliation: Hadassah university hospital of Jerusalem
name: Polina Stepensky, prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kfir-Erenfeld S, Asherie N, Grisariu S, Avni B, Zimran E, Assayag M, Sharon TD, Pick M, Lebel E, Shaulov A, Cohen YC, Avivi I, Cohen CJ, Stepensky P, Gatt ME. Feasibility of a Novel Academic BCMA-CART (HBI0101) for the Treatment of Relapsed and Refractory AL Amyloidosis. Clin Cancer Res. 2022 Dec 1;28(23):5156-5166. doi: 10.1158/1078-0432.CCR-22-0637.