A Study of OL-101 Injection in Patients with Relapsed or Refractory Multiple Myeloma (RRMM)

Zhejiang University

Status and phase

Enrolling

Phase 1

Conditions

Multiple Myeloma

Treatments

Biological: OL-101 infusion

Study type

Interventional

Funder types

Other

Identifiers

NCT06644118

OL-101-001

Details and patient eligibility

About

This clinical trial aims to characterize the safety of OL-101 and establish the recommended dose for future research and to evaluate the efficacy of OL-101 (Dose expansion).

Full description

This study will evaluate the safety and efficacy of OL-101, a chimeric antigen receptor T cell (CAR-T) therapy directed against B-Cell Maturation Antigen (BCMA) and G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D). This study is a single-arm, open-label, early exploratory clinical trial, conducted in two phases: dose escalation and dose expansion in adults with multiple myeloma. The trial begins with the dose-escalation phase that focus on safety and tolerability, with interval assessments for potential dose escalation or de-escalation. Recommended dose will be selected at the completion of the dose escalation stage in the dose expansion stage. The study aims to assess safety, pharmacokinetic/pharmacodynamic profiles, and efficacy.

Enrollment

58 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Documented diagnosis of multiple myeloma according to the 2014 IMWG diagnostic criteria
Relapsed/refractory multiple myeloma as defined by:
1. Received at least 3 prior lines of MM treatment (must include a PI, an IMiD, and an anti-CD38 antibody).
2）Disease progression within 12 months of the most recent anti-MM therapy; or disease progression within the past 6 months and subsequently lack response to the most recent line of therapy.
Measurable disease at screening as defined by any of the following:
1. Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or
2. Light chain multiple myeloma without measurable disease in the serum or the urine: Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.
Positive expression of either BCMA or GPRC5D on bone marrow plasma cells; must be GPRC5D expression positive if previously received BCMA targeted therapy
ECOG 0-1
Expected life expectancy exceeds 12 weeks
Adequate bone marrow reserve or organ function meeting the following criteria:
1. Hemoglobin ≥ 70 g/L
2. Platelet count ≥ 50 × 10^9/L
3. Absolute lymphocyte count ≥ 0.3×10^9/L
4. Absolute neutrophil count ≥ 1.0 × 10^9/L
5. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal (ULN)
6. Total bilirubin ≤ 2 times ULN; except in subjects with congenital bilirubinemia (such as Gilbert syndrome, in which case the direct bilirubin ≤1.5 × ULN is required)
7. Creatinine clearance ≥ 60 mL/min (calculated by Cockcroft-Gault equation).
8. corrected serum calcium ≤12.5 mg/dL (≤3.1 mmol/L) or free ionized calcium ≤6.5 mg/dl (≤1.6 mmol/L)
9. SpO2>92% on room air
10. Left ventricular ejection fraction (LVEF) ≥ 50% as assessed by echocardiogram; no clinically meaningful pericardial effusion by ultrasound

Exclusion criteria

Solitary plasmacytoma
Known active central nervous system (CNS) involvement or exhibits clinical signs of CNS involvement of multiple myeloma.
Received allogeneic stem cell transplant; received autologous stem cell transplant within 12 weeks before screening
Active second primary malignant tumor, exclude the following: cured non- melanoma skin cancer, non-metastatic prostate cancer, cervical carcinoma in situ, ductal or lobular carcinoma in situ of the breast
Any other significant medical disease, abnormality, or condition that, in the investigator judgment, may make the patient unsuitable for participation in the study or put the patient at risk.
Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome, or primary AL amyloidosis.