Light Chain Amyloidosis, Multiple Myeloma, Refractory to Standard Treatment, Multiple Myeloma, Relapsed
Conditions
Keywords
Relapsed/Refractory Multiple Myeloma, Light-Chain Amyloidosis, B-cell maturation antigen (BCMA), Autologous CAR-T
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.
Interventions
BIOLOGICALHBI0101 CART
HBI0101 CART 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 HBI0101 CART may be provided fresh or cryopreserved.
Sponsors
Polina Stepensky
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical response to HBI0101 CART | 24 months | Percentage of subjects who achieved partial response (PR) or better |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate | 24 months | Overall Response Rate is defined by proportion of subjects with Partial Response or better per International Myeloma Working Group (IMWG) Criteria for MM, and Partial Response or better per Hematologic Response Criteria for AL. |
| Overall survival | 24 months | Overall Survival is defined by the date of the initial infusion of HBI010 CART cells to the date of the patient's death due to any cause. If the patient is alive or the vital status is unknown, then their data will be censored at the date they were last known to be alive. |
| Progression-free survival | 24 months | Progression-Free Survival is defined as the time from the date of the initial infusion of HBI0101 CART to the date of first documented disease progression, or death due to any cause, whichever occurs first. This is defined as Stable Disease (or better) per IMWG Criteria for MM, and Partial Response or better per Hematologic Response Criteria for AL. |
| Safety of HBI0101 CART | 24 months | Incidence of Serious Adverse Events and Adverse Events of Special Interest related to study treatment |
| Disease-free survival | 24 months | Disease-Free Survival proportion of MRD evaluable subjects who are MRD negative is defined as the duration from start of complete response until the time of relapse from complete response. Minimal Residual Response (MRD) is defined as the absence of clonal plasma cells on bone marrow aspirate (minimum test sensitivity to detect 1 in 105 nucleated cells (10-5 threshold)). |
| Persistence of HBI0101 CART cells | 24 months | Quantification of HBI0101 CART cells in the blood over time |
| Organ response | 24 months | Frequency of organ response (including cardiac, renal, and hepatic responses) in subject with Light-chain Amyloidosis |
| Duration of response | 24 months | Duration of response is defined as the first observation of partial response (for patients undergoing bridging therapy, this may be the date of the initial CAR T-cell infusion), to the time of disease progression, with deaths from causes other than progression censored. |
Countries
Israel
Contacts
Primary ContactPolina Stepensky, MD
Outcome results
None listed