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

NCT ID: NCT07106684

Last Updated: 2025-08-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-10
• Study Completion Date: 2029-08-01

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.

Conditions

Multiple Myeloma, Plasma Cell Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ASCT Combined With BCMA CAR-T and GPRC5D/CD3 BiTEs Maintenance

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.

Group Type: EXPERIMENTAL

Autologous hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Patients receive transplantation conditioning followed by autologous hematopoietic stem cell transplantation after successful stem cell mobilization and collection.

BCMA CAR-T

Intervention Type: BIOLOGICAL

Patients will receive BCMA CAR-T single dose (3.0 x 10\^6 cells /kg) infusion 3 days after ASCT.

GPRC5D/CD3 BiTEs

Intervention Type: DRUG

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

Interventions

Autologous hematopoietic stem cell transplantation

Patients receive transplantation conditioning followed by autologous hematopoietic stem cell transplantation after successful stem cell mobilization and collection.

Intervention Type: PROCEDURE

BCMA CAR-T

Patients will receive BCMA CAR-T single dose (3.0 x 10\^6 cells /kg) infusion 3 days after ASCT.

Intervention Type: BIOLOGICAL

GPRC5D/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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute of Hematology & Blood Diseases Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Gang An, PhD&MD

Role: CONTACT

angang@ihcams.ac.cn

86-022-23909171

Facility Contacts

Gang An

Role: primary

angang@ihcams.ac.cn

86-022-23909171

Other Identifiers

IIT2025048

Identifier Type: -

Identifier Source: org_study_id