Multiple Myeloma, Plasma Cell Leukemia
Conditions
Keywords
Plasma cell leukemia, CAR-T, ASCT, BiTEs
Brief summary
This is a prospective, single-arm, phase II study to evaluate the efficacy and safety of autologous stem cell transplantation combined with BCMA CAR-T therapy followed by GPRC5D/CD3 bispecific antibody maintenance in transplant-eligible patients with primary plasma cell leukemia.
Detailed description
All subjects will receive standard induction therapy for up to four cycles prior to screening. Following response evaluation, those who meet the inclusion criteria will be enrolled. Enrolled patients will undergo autologous stem cell transplantation (ASCT) combined with BCMA CAR-T cell therapy, followed by GPRC5D/CD3 bispecific antibody therapy. Patients who achieve a stringent complete response (sCR) and sustained MRD negativity (≥12 months) will receive maintenance therapy for 24 months, and may then enter a treatment-free observation phase. Patients who experience MRD resurgence or loss of response during observation will resume maintenance therapy. Patients who do not achieve both sCR and sustained MRD negativity (≥12 months) will continue GPRC5D/CD3 bispecific antibody therapy until disease progression or unacceptable toxicity.
Interventions
PROCEDUREAutologous hematopoietic stem cell transplantation
Patients receive transplantation conditioning followed by autologous hematopoietic stem cell transplantation after successful stem cell mobilization and collection.
BIOLOGICALBCMA CAR-T
Patients will receive BCMA CAR-T single dose (3.0 x 10\^6 cells /kg) infusion 3 days after ASCT.
DRUGGPRC5D/CD3 BiTEs
Patients will receive GPRC5D/CD3 BiTEs maintenance therapy at a dose of 54 μg/kg every 4 weeks, starting 3 months after BCMA CAR-T infusion and continuing for at least 2 years
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years and ≤ 70 years. 2. Participants with documented newly-diagnosed primary plasma cell leukemia according to IMWG diagnostic criteria. 3. Measurable disease at screening, defined as: Serum M-protein level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio. 4. Patients deemed eligible for high-dose chemotherapy with ASCT. 5. Tumor cells were BCMA and GPRC5D positive. 6. Serum total bilirubin \<2 x upper limit of normal (ULN), serum AST and ALT \<3 x ULN, creatinine clearance ≥ 30mL/min (Cockroft-Gault formula). 7. Informed Consent/Assent: All subjects have the ability to understand and the willingness to sign a written informed consent.
Exclusion criteria
1. Active amyloidosis. 2. Central nervous system involvement. 3. Prior BCMA-targeted therapy or CAR-T therapy. 4. Active hepatitis B or hepatitis C virus infection. 5. Known HIV infection. 6. Life expectancy \<6 months. 7. Woman who are pregnant or breastfeeding 8. Evidence of uncontrolled dysfunction of heart, lung, brain, and other important organs. 9. Any other conditions that are not eligible for the trial in the judgement of the principal investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained MRD-negative rate | Up to 2 year | Rate of patients achieving sustained MRD negativity for more than 12 months |
| MRD negativity rate | Up to 2 years | Rate of patients achieving MRD negativity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | Up to 2 year | The incidence of treatment-emergent adverse events (TEAEs) |
| Complete response rate (CRR) | Up to 2 years | CR or better is defined as percentage of participants who achieve a CR response or Stringent Complete Response (sCR) response accoording to the IMWG criteria |
| Progression free survival (PFS) | Up to 3 year | Progression free survival is defined as the time from the date of diagnosis to the date of first documented PD, as defined in the IMWG criteria, or death due to any cause, whichever occurs first |
| Overall survival (OS) | Up to 5 year | Overall survival is defined as the time from the date of diagnosis to the date of death due to any cause |
Countries
China
Contacts
Primary ContactGang An, PhD&MD
Outcome results
None listed