ASCT Combined With BCMA CAR-T and GPRC5D/CD3 BiTEs Maintenance for Transplant-Eligible Primary Plasma Cell Leukemia

Not Applicable

Recruiting

• Conditions: Multiple Myeloma, Plasma Cell Leukemia
• Interventions: Procedure: Autologous hematopoietic stem cell transplantation; Biological: BCMA CAR-T; Drug: GPRC5D/CD3 BiTEs

• Registration Number: NCT07106684
• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital, China

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.

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-30
• Study First Submitted QC: 2025-07-30
• Last Update Submitted: 2025-07-30
• Study First Posted: 2025-08-06
• Last Update Posted: 2025-08-06
• Study Start: 2025-08-10
• Primary Completion: 2027-08-01
• Study Completion: 2029-08-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ASCT Combined With BCMA CAR-T and GPRC5D/CD3 BiTEs Maintenance	Autologous hematopoietic stem cell transplantation	Patients will receive induction therapy, undergo ASCT followed by BCMA CAR-T infusion. Three month after CAR-T cell infusion, patients will begin GPRC5D/CD3 BiTEs maintenance therapy for ≥2 years.
ASCT Combined With BCMA CAR-T and GPRC5D/CD3 BiTEs Maintenance	BCMA CAR-T	Patients will receive induction therapy, undergo ASCT followed by BCMA CAR-T infusion. Three month after CAR-T cell infusion, patients will begin GPRC5D/CD3 BiTEs maintenance therapy for ≥2 years.
ASCT Combined With BCMA CAR-T and GPRC5D/CD3 BiTEs Maintenance	GPRC5D/CD3 BiTEs	Patients will receive induction therapy, undergo ASCT followed by BCMA CAR-T infusion. Three month after CAR-T cell infusion, patients will begin GPRC5D/CD3 BiTEs maintenance therapy for ≥2 years.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences; 🇨🇳 Tianjin, Tianjin, China