Study of NXC-201 CAR-T in Patients With Light Chain (AL) Amyloidosis

NCT06097832 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NXC-201-AL-001
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 18

Brief Summary

Open-label Phase 1b Dose Escalation/Dose Expansion study exploring the safety and efficacy of NXC-201 in patients with relapsed or refractory light chain amyloidosis (AL).

Conditions

Light Chain (AL) Amyloidosis

Keywords

Relapsed refractory AL amyloidosis; R/R AL amyloidosis

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Treatment-Related Adverse Events

  An adverse event (AE) can be any unfavorable and unintended sign (including an abnormal. laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product.

  24 months

• Number of Participants with Adverse Events by Severity as Assessed by CTCAE v5.0

  An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0, with the exception of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS should be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading.

  24 months

• To confirm the maximum tolerated dose (MTD)

  According to Common Terminology Criteria for Adverse Events (CTCAE) criteria, version 5.0, and Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) per American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading

  24 months

• To confirm the recommended phase 2 dose (RP2D)

  According to Common Terminology Criteria for Adverse Events (CTCAE) criteria, version 5.0, and Cytokine release syndrome (CRS) and Immune effector cell-associated neurotoxicity syndrome (ICANS) per American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading

  24 months

Secondary Outcomes (1)

• Percentage of participants with hematologic and organ response

  24 months

Study Arms (1)

NXC-201 CAR-T

EXPERIMENTAL

The dose escalation phase will include the following doses: Cohort 1 - 150×10\^6 CAR-positive (CAR+) T cells (3 patients) Cohort 2 - 450×10\^6 CAR-positive (CAR+) T cells (3 patients) The dose expansion phase will then proceed.

Biological: NXC-201 CAR-T

Interventions

NXC-201 CAR-T BIOLOGICAL

NXC-201 (formerly HBI0101) CAR-T is defined as autologous T cells transduced ex-vivo with anti-BCMA CAR retroviral vector encoding the chimeric antigen receptor (CAR) targeted to human BCMA. The NXC-201 CAR-T is provided fresh without cryopreservation.

Also known as: HBI0101 CAR-T

NXC-201 CAR-T

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age.
• Voluntarily signed informed consent form (ICF).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Histologically proven systemic AL amyloidosis confirmed by positive Congo red staining with green birefringence on polarized light microscopy in an organ outside the bone marrow and evidence of a measurable clonal plasma cell disease that requires active treatment.
• An underlying plasma cell disorder can be identified by one of the following: clonal plasma cells in the BM, monoclonal protein in the serum or urine, or abnormal free light chain ratio.
• Because AL amyloidosis may present with low volumes of bone marrow plasma cells, prior biopsies demonstrating clonal plasma cell populations may be used to determine eligibility.
• Measurable hematologic disease: difference between involved and uninvolved FLC \> 20 mg/L (or 2mg/dl) with an abnormal k/l ratio; or M-spike \> 0.5mg/dl.
• Symptomatic organ involvement (heart, kidney, liver/GI tract, peripheral nervous system).
• 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.
• Absence of any psychological, familial, sociological, or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before trial entry.
• Able to swallow pills.

You may not qualify if:

• Prior treatment with CAR T therapy directed at any target.
• Any therapy that is targeted to BCMA.
• Stroke or seizure within 6 months of signing ICF.
• Bone marrow plasma cells \>30% and clinically symptomatic multiple myeloma with end organ damage (i.e. lytic bone lesions).
• New York Heart Association Heart Failure Class III or Class IV.
• Any prior systemic therapy for AL amyloidosis within 14 days prior to leukapheresis.
• Therapeutic doses of steroids within 2 weeks prior to leukapheresis (Physiological replacement doses of steroids are allowed up to 12 mg/m2/d hydrocortisone or equivalent).
• Any prior systemic therapy for AL amyloidosis within 14 days of leukapheresis.
• Wash-out period of at least 4 weeks from previous investigational treatment prior to leukapheresis.
• Inadequate hepatic function:
• Aspartate aminotransferase (AST \[SGOT\] or alanine aminotransferase (ALT \[SGPT\]) \>3 x upper limit of normal (ULN) value
• Alkaline phosphatase \>2 times ULN
• Serum direct bilirubin \>2 times ULN
• Inadequate renal function: creatinine clearance (CRCL) \<20 mL/min.
• Inadequate bone marrow function prior to leukapheresis or lymphodepletion, without transfusion or growth factor support within 5 days prior defined by absolute neutrophil count (ANC) \<1000 cells/mm3, platelet count \<50,000/mm3, or hemoglobin \<8 g/dL (blood transfusions are allowed), absolute lymphocyte count \< 300 cells/mm3.

Sponsors & Collaborators

• Nexcella Inc.: lead
• Immix Biopharma, Inc.: collaborator

Study Sites (18)

Sutter Health Alta Bates

Berkeley, California, 94704, United States

RECRUITING

City of Hope

Duarte, California, 91010, United States

RECRUITING

University of California Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

University of California Davis Medical Center

Sacramento, California, 95817, United States

RECRUITING

Stanford University

Stanford, California, 94305, United States

RECRUITING

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

The University of Kansas Cancer Center

Fairway, Kansas, 66205, United States

RECRUITING

Tufts Medical Center

Boston, Massachusetts, 02111, United States

RECRUITING

Boston University Medical Center

Boston, Massachusetts, 02118, United States

RECRUITING

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

Washington University Siteman Cancer Center

St Louis, Missouri, 63110, United States

RECRUITING

Memorial Sloan Kettering Comprehensive Cancer Center

New York, New York, 10065, United States

RECRUITING

University of Cincinnati Cancer Center

Cincinnati, Ohio, 45267, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Baptist Memorial Hospital

Memphis, Tennessee, 381202127, United States

RECRUITING

Huntsman Cancer Institute at the University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Swedish Cancer Institute

Seattle, Washington, 98104, United States

RECRUITING

Related Publications (3)

• 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.

  PMID: 36107221 BACKGROUND

• Asherie N, Kfir-Erenfeld S, Avni B, Assayag M, Dubnikov T, Zalcman N, Lebel E, Zimran E, Shaulov A, Pick M, Cohen Y, Avivi I, Cohen C, Gatt ME, Grisariu S, Stepensky P. Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial. Haematologica. 2023 Jul 1;108(7):1827-1839. doi: 10.3324/haematol.2022.281628.

  PMID: 36200421 BACKGROUND

• Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, Schonland S, Hegenbart U, Comenzo R, Kastritis E, Dimopoulos MA, Jaccard A, Klersy C, Merlini G. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012 Dec 20;30(36):4541-9. doi: 10.1200/JCO.2011.37.7614. Epub 2012 Oct 22.

  PMID: 23091105 BACKGROUND

MeSH Terms

Conditions

Amyloidosis; Immunoglobulin Light-chain Amyloidosis

Condition Hierarchy (Ancestors)

Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Central Study Contacts

Nexcella

CONTACT

310-773-0664; clinicaltrials@nexcella.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label single-arm clinical study of NXC-201 CAR-T will proceed sequentially through dose cohorts as follows: Cohort 1 - 150×10\^6 CAR-positive (CAR+) T cells (3 patients) Cohort 2 - 450×10\^6 CAR-positive (CAR+) T cells (3 patients) The dose expansion phase will then proceed.

Study Record Dates

• First Submitted: October 14, 2023
• First Posted: October 24, 2023
• Study Start: June 5, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2039
• Last Updated: July 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (18)