Multiple myeloma patients with early relapse after upfront autologous stem cell transplantation or primary refractory disease Relapsed and/or refractory MM, relapsed MM after ASCT
Conditions
Interventions
All patients received lymphodepleting chemotherapy (LDT) with intravenous fludarabine 30 mg/m2 and intravenous cyclophosphamide 300 mg/m2 daily for 3 consecutive days, followed by a single infusion of
Experimental Drug
BCMA-targeted/CD28-containing CAR T cell
Sponsors
Ramathibodi Foundation
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Age between 18 and 70 years. 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. 3. Diagnosis of multiple myeloma with disease relapse following ASCT, or primary refractory multiple myeloma unresponsive to at least two prior lines of therapy comprising a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), or an anti-CD38 monoclonal antibody (daratumumab). 4. Presence of active measurable disease, defined by at least one of the following criteria 4.1 Serum M-protein 0.5 g/dL or greater 4.2 Urine M-protein 200 mg/24 hours or greater 4.3 Serum free light chain (FLC) assessment showing involved FLC 10 mg/dL or greater (100 mg/L) or an abnormal involved-to-uninvolved FLC ratio. 5. Ability to comply with the study protocol and follow-up procedures. Patients of childbearing potential must agree to use effective contraception for at least 12 months following anti-BCMA CAR T-cell infusion, or until CAR T-cells become undetectable in the body as confirmed by at least two negative polymerase chain reaction (PCR) assays. 6. Adequate organ functions, defined as follows: 6.1 Glomerular filtration rate (GFR) greater than 45 mL/min/1.73 m2 or serum creatinine less than 1.0 mg/dL (or within the normal reference range for the patient's age and sex). 6.2 Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels less than 3 times the upper limit of normal (ULN) for age. 6.3 Total bilirubin less than 3.0 mg/dL or less than 1.5 times the ULN for age. 6.4 Oxygen saturation (pulse oximetry) 92% or more on room air, and a normal FEV1 to FVC ratio by spirometry. 6.5 Left ventricular ejection fraction (LVEF) 45% or more, as assessed by echocardiography or multiple-gated acquisition (MUGA) scan within one month prior to study enrollment.
Exclusion criteria
Exclusion criteria: 1. Presence of central nervous system (CNS) involvement or the presence of malignant cells in the cerebrospinal fluid (CSF). 2. Active or prior diagnosis of plasma cell leukemia, primary AL amyloidosis, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome, or Waldenstrom macroglobulinemia. 3. Concurrent malignancy or a prior history of another malignancy aside from multiple myeloma. 4. Prior allogeneic hematopoietic stem cell transplantation (alloHSCT). 5. Concurrent use of systemic immunosuppressive therapy. 6. Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV). 7. Pregnant or currently breastfeeding (lactating) females. 8. Presence of uncontrolled comorbidities or psychiatric disorders that could compromise patient safety or interfere with study participation. 9. History of alcohol or substance abuse that could potentially affect the safety of the study treatments or patient compliance with the study protocol. 10. Administration of any vaccine within 28 days prior to study enrollment. 11. Concurrent enrollment in another interventional clinical trial or receiving other investigational agents. 12. Known allergy or hypersensitivity to the mandatory study medications, such as fludarabine or cyclophosphamide.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety profile Within one year after end of the intervention Cytokine release syndrome (CRS), immune cell-associated neurotoxicities (ICANS), acute graft-versus-host disease (GVHD), infectious complications, and laboratory abnormalities | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy Within one year after end of the intervention ORR, CR rate, PFS, OS,Exploratory endpoints Within one year after end of the intervention Cellular kinetics (in vivo expansion of anti-CD19 CAR T cells in the peripheral blood), hypogammaglobulinemia (defined as serum immunoglobulin G (IgG) level below 700 mg/dL), and B-cell aplasia | — |
Countries
Thailand
Contacts
Public ContactThanakrit Piyajaroenkij
Division of Hematology, Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Outcome results
None listed