Clinical trial NCT06971380: Study of HBI0101 (NXC-201) CAR-T Therapy in Multiple Myeloma and Light-Chain Amyloidosis
Official title: A Phase 2 Trial to Study Efficacy and Safety of HBI0101 (NXC-201) CART in Subjects With Multiple Myeloma and Light-Chain Amyloidosis.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma, Refractory to Standard Treatment
Multiple Myeloma, Relapsed
Light Chain Amyloidosis
Keywords: Relapsed/Refractory Multiple Myeloma
Light-Chain Amyloidosis
B-cell maturation antigen (BCMA)
Autologous CAR-T
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
First posted: 2025-05-14
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Phase II study of HBI0101 (NXC-201) BCMA-CART in Multiple Myeloma and Light-chain Amyloidosis Patients. The goal of the study is to evaluate the efficacy and safety of HBI0101 CART.

Detailed description: Up to 180 subjects with relapsed/refractory (R/R) multiple myeloma (MM) or light chain amyloidosis (AL) will be enrolled in a single-arm, open-label, single-site Phase 2 study. Eligible subjects will undergo leukapheresis procedure to provide starting material for manufacturing of HBI0101 CART investigational product. Each eligible subject will receive a single dose of HBI0101 CART cells. Prior to administration of HBI0101 CART, the study subjects will undergo lymphodepletion. Following administration of HBI0101 CART the subjects will be hospitalized for several days and then will return for routine follow-up periodical visits until 24 months after infusion.

Eligibility criteria: Inclusion Criteria:

1. ≥18 years of age at the time of signing informed consent.
2. Voluntarily signed informed consent form.
3. Diagnosis of multiple myeloma and/or light-chain amyloidosis with relapsed or refractory disease, with measurable disease at screening visit
4. Subject suffering from multiple myeloma must have been exposed to at least two prior lines of therapy including proteasome inhibitor, immunomodulatory (IMiDs) therapy or anti-CD38 antibody, or functionally high-risk patients (i.e. first relapse within 18 months of treatment initiation) may be included.

   Subject with amyloidosis must have been exposed to at least one prior line of therapy which includes proteasome inhibitor or anti-CD38 antibody, or subjects with insufficient response (i.e. not achieving a VGPR or CR after exposure to at least an anti-CD38 antibody and a proteasome inhibitor) may be included.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2.
6. Women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or tubal ligation or who has not been naturally postmenopausal for at least 24 consecutive months, 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.
7. Recovery to ≤ Grade 2 or baseline of any non-hematologic toxicities due to prior treatments, excluding alopecia and Grade 3 neuropathy.
8. Ability and willingness to adhere to the study visit schedule and all protocol requirements.
9. Subjects with relapsed multiple myeloma who have previously undergone allogenic stem cell transplantation must have no evidence of graft versus host disease after cessation of any immunosuppressive therapy for at least one month before recruitment to the study.

Exclusion Criteria:

1. Contraindication to a study treatment/procedure or is anticipated to receive treatment/procedure that may preclude performance of study procedures.
2. Known bulky central nervous system disease.
3. Inadequate hepatic function defined by aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 2.5 x upper limit of normal (ULN) and direct bilirubin \> 4x ULN.
4. Inadequate renal function defined by serum creatinine clearance/estimated clearance of \<20(ml/min).
5. International ratio (INR) or partial thromboplastin time (PTT) \> 2 x ULN, unless on a stable dose of anticoagulant for a thromboembolic event (provided this event is not an exclusion criteria).
6. Inadequate bone marrow function defined by absolute neutrophil count (ANC) \< 1000 cells/mm\^3, platelet count \< 30,000 mm\^3, or hemoglobin \< 8 g/dL. Subjects with absolute lymphocyte count \< 300 cells/mm\^3 may be excluded (due to potential challenges with producing CART cells), per investigator judgement.
7. Echocardiogram with left ventricular ejection fraction \< 40%.
8. Ongoing treatment with chronic immunosuppressant such as cyclosporine or systemic steroids (physiological replacement doses of steroids are allowed up to 12 mg/m\^2/d hydrocortisone or equivalent)
9. Significant co-morbid condition or disease which in the judgment of the Investigator would place the subject at undue risk or interfere with the study; examples include, but are not limited to, cirrhotic liver disease, sepsis, recent significant traumatic injury, and other conditions.
10. Known human immunodeficiency virus (HIV) positive status.
11. Active Hepatitis B or Hepatitis C active infection.
12. Active CMV infection.
13. Known history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within 3 months.
14. Chronic atrial fibrillation with uncontrolled heart rate.
15. Second primary malignancies that has required therapy in the last 2 years or is not in complete remission.
16. Subjects who have had a venous thromboembolic event (e.g., pulmonary embolism or deep vein thrombosis) requiring anticoagulation and who meet any of the following criteria:

    1. Have been on a stable dose of anticoagulation for \< 1 month (except for acute line insertion induced thrombosis.)
    2. Have had a Grade 2, 3, or 4 hemorrhage in the last 30 days
    3. Are experiencing continued symptoms from their venous thromboembolic event (e.g. continued dyspnea or oxygen requirement).
17. Pregnant or lactating women.
18. Participation in another interventional clinical trial within 30 days prior to screening visit.

Primary outcomes:
measure: Clinical response to HBI0101 CART
timeFrame: 24 months
Secondary outcomes:
measure: Safety of HBI0101 CART
timeFrame: 24 months
measure: Overall response rate
timeFrame: 24 months
measure: Overall survival
timeFrame: 24 months
measure: Progression-free survival
timeFrame: 24 months
measure: Duration of response
timeFrame: 24 months
measure: Disease-free survival
timeFrame: 24 months
measure: Persistence of HBI0101 CART cells
timeFrame: 24 months
measure: Organ response
timeFrame: 24 months
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah MO
Study officials:
References:
citation: 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.
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.