Light Chain (AL) AmyloidosisPhase 1/2NEXICART-2NCT06097832
Study of NXC-201 CAR-T in Patients With Light Chain (AL) Amyloidosis
A Phase 1/2 study testing NXC-201 CAR-T in people with Light Chain (AL) Amyloidosis, run by Nexcella Inc. at 18 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Light Chain (AL) Amyloidosis
- What is being tested?
- NXC-201 CAR-T
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 18 sitesUnited States
- Study dates
- 5 Jun 2024to Jan 2039
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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.
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- 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.
- Patients should have received at least one line of therapy with a CD38 monoclonal antibody and a proteosome inhibitor and not be in VGPR or CR at the time of inclusion. Patients who did not reach VGPR after two cycles of initial therapy or patients who did achieve VGPR or better but with a hematological relapse can be included.
- 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.
Who cannot join
- 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.
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- 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.
- International ratio (INR) or partial thromboplastin time (PTT) >1.5 x ULN, unless on a stable dose of anticoagulant for a thromboembolic event that does NOT meet exclusion criteria.
- 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.
- Presence of active infection within 72 hours prior to lymphodepletion.
- Significant co-morbid condition/s or disease/s which in the judgment of the Investigator would place the subject at undue risk or interfere with the study.
- Known human immunodeficiency virus (HIV) positive status subjects who have not achieved undetectable viral load on highly active anti-retroviral therapy/combination anti-retroviral therapy (HAART/cART) within 6 months of lymphodepletion (previously treated HIV with undetectable viral load can be included)
- Patients with active Hepatitis B or Hepatitis C with detectable viral load (previously treated Hepatitis B or Hepatitis C with undetectable viral load can be included)
- Subjects with a history of stroke, unstable angina, or myocardial infarction requiring medication or mechanical control within 3 months.
- Evidence of clinically significant ventricular arrhythmias on 7-day Zio® patch (or equivalent device) monitoring despite anti-arrhythmic treatment, except if a pacemaker or automated implantable cardioverter defibrillator (AICD) has been implanted.
- Stage IIIb patients:
- NT-proBNP >8500 ng/L and
- hs-troponin I ≥100 ng/L or troponin I ≥0.1 mcg/L or troponin T ≥ 0.035 mcg/L or hs-troponin T ≥50 ng/L
- Left ventricular ejection fraction <35%.
- Heart failure which is, in the opinion of the Investigator, related to ischemic heart disease.
- Presence of other active malignancy that requires treatment with the exception of non-melanoma skin cancer, cervical cancer, treated early-stage prostate cancer provided that prostate specific antigen is within normal limit, or any completely resected carcinoma in situ; other indolent/completely resected malignancies may be discussed with the Principal Investigator (PI) and/or Co-PI.
- Subjects who have had a venous thromboembolic event requiring anticoagulation and who meet any of the following criteria:
- Have been on a stable dose of anticoagulation for < 1 month (except for acute line insertion induced thrombosis).
- Have had a Grade 2, 3, or 4 hemorrhage in the last 30 days.
- Are experiencing continued symptoms from their venous thromboembolic event (e.g., continued dyspnea or oxygen requirement).
- Presence of non-AL amyloidosis.
- AL amyloidosis with isolated soft tissue involvement.
- Supine systolic blood pressure <100 mmHg or postural symptoms despite medical therapy.
- Subject is a woman who is pregnant, or breast-feeding, or planning to become pregnant.
- Subjects with known/underlying medical conditions that, in the investigator's opinion would make the administration of the study drug hazardous (i.e., chronic obstructive pulmonary disease, persistent asthma, uncontrolled diabetes or uncontrolled coronary artery disease).
- Chronic atrial fibrillation with uncontrolled heart rate.
- Unwillingness to practice effective birth control.
- Inability to comply with other requirements of the protocol.
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322
Sutter Health Alta Bates
Berkeley, California, 94704
Tufts Medical Center
Boston, Massachusetts, 02111
Boston University Medical Center
Boston, Massachusetts, 02118
University of Cincinnati Cancer Center
Cincinnati, Ohio, 45267
Cleveland Clinic
Cleveland, Ohio, 44195
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, 48201
City of Hope
Duarte, California, 91010
The University of Kansas Cancer Center
Fairway, Kansas, 66205
University of California Los Angeles
Los Angeles, California, 90095
Baptist Memorial Hospital
Memphis, Tennessee, 381202127
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, 55455
Memorial Sloan Kettering Comprehensive Cancer Center
New York, New York, 10065
University of California Davis Medical Center
Sacramento, California, 95817
Huntsman Cancer Institute at the University of Utah
Salt Lake City, Utah, 84112
Swedish Cancer Institute
Seattle, Washington, 98104
Washington University Siteman Cancer Center
St Louis, Missouri, 63110
Stanford University
Stanford, California, 94305
About this study
Official title: Phase 1b/2 Study of NXC-201 for the Treatment of Patients With Relapsed or Refractory AL Amyloidosis
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).
Read the detailed description
Building on the prior NXC-201 results in AL amyloidosis published by Kfir-Erenfeld et. al (2022) and Asherie et. al. (2023), this study will enroll additional patients with relapsed or refractory AL amyloidosis and assess the safety and efficacy of NXC-201.
Subjects with relapsed/refractory AL amyloidosis will undergo leukapheresis at least one month prior to lymphodepletion, to provide starting material for NXC-201 CART manufacture. Subjects will be treated according to the following process for lymphodepletion: Days -5, -4 and -3 Cyclophosphamide 250mg/m2, IV infusion over 30 mins, followed immediately by Fludarabine 25 mg/m2 IV infusion over 30 minutes.
NXC-201 CART is administered on Day 0, after lymphodepletion.
Enrolled subjects will receive a dose of NXC-201 CAR-positive (CAR+) T cells. Dose escalation and expansion will be guided by safety review committee.
- Conditions
- Light Chain (AL) Amyloidosis
- Being tested
- NXC-201 CAR-T
- Keywords
- Relapsed refractory AL amyloidosis, R/R AL amyloidosis
- Medical subject headings
- Amyloidosis, Immunoglobulin Light-chain Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NXC-201 CAR-TBiological
Also called HBI0101 CAR-T
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: NXC-201 CAR-T |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 24 months
Secondary outcomes (1)
Percentage of participants with hematologic and organ response
According to consensus recommendations for AL amyloidosis treatment response criteria in AL (Palladini, 2012)
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2023
- Study start5 Jun 2024
- Primary completionDec 2026 (estimated)
- Study completionJan 2039 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Light Chain (AL) AmyloidosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nexcella Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Immix Biopharma, Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06097832
- Sponsor's protocol ID
- NXC-201-AL-001
- Acronym
- NEXICART-2
- Status last verified
- Jul 2026
- First submitted
- 14 Oct 2023
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There will be no individual participant data sharing
Publications
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.
PubMed 36107221Asherie 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.
PubMed 36200421Palladini 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.
PubMed 23091105Al Haddad N, Brailovski E, Dela-Pena J, Cook M, Rosenzweig M, Jolie Landau H. BCMA CAR T for AL Amyloidosis After Plasmacytic Relapse of Lymphoplasmacytic Lymphoma. EJHaem. 2026 Jun 16;7(3):e70329. doi: 10.1002/jha2.70329. eCollection 2026 Jun.
PubMed 42312318