ASCT Combined With BCMA CAR-T and GPRC5D/CD3 BiTEs Maintenance for Transplant-Eligible Primary Plasma Cell Leukemia (CAREMM-004)

Institute of Hematology & Blood Diseases Hospital, China

Status and phase: Enrolling; Phase 2

Conditions: Multiple Myeloma, Plasma Cell Leukemia

Treatments: Drug: GPRC5D/CD3 BiTEs; Biological: BCMA CAR-T; Procedure: Autologous hematopoietic stem cell transplantation

Study type: Interventional

Funder types: Other

Identifiers

NCT07106684

IIT2025048

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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20 participants in 1 patient group

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

Experimental group

Description:

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.

Treatment:

Procedure: Autologous hematopoietic stem cell transplantation

Drug: GPRC5D/CD3 BiTEs

Biological: BCMA CAR-T