A Phase I Trial to Establish the Safety and Maximum Tolerated Dose of High-affinity Autologous BCMA-targeting CAR T-cells in Patients With Relapsed and Refractory B-cell Malignancies
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Neoplasms
- Sponsor
- Technische Universität Dresden
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Incidence and severity of adverse events and serious adverse events
- Status
- Recruiting
- Last Updated
- 8 months ago
Overview
Brief Summary
The purpose of this phase I study is to determine whether MDC-CAR-BCMA001 (BCMA directed CAR T-cells) is safe and tolerable in the treatment of relapsed and refractory B-cell malignancies
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patients aged ≥ 18 years
- •Written informed consent of the subject
- •Able and willing to adhere to the trial protocol
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Either Multiple Myeloma (MM):
- •relapsed or refractory disease after at least 2 lines of treatment including an Immunomodulatory drug, a proteasome inhibitor and an anti-cluster of differentiation 38 antibody or anti-cluster of differentiation 319 (SLAMF7; Elotuzumab) antibody AND
- •not eligible for treatment with other regimen available according to local standard of care and known to confer clinical benefit according to the investigator's discretion, prior treatment with other BCMA-targeting immunotherapies (including T-cell engaging antibodies, CAR T-cells and antibody-drug immuno-conjugates) is allowed AND
- •measurable disease defined by serum M-Protein ≥ 10 g/l OR urine M-Protein ≥ 200 mg/24h OR serum free light chain \> 100 mg/l of involved free light chain and abnormal serum free light chain ratio
- •Diffuse large B-cell lymphoma (DLBCL):
- •Relapsed after or refractory to standard curative therapy (such as R-CHOP) and refractory to at least one course of standard salvage chemotherapy OR
Exclusion Criteria
- •Any Central nervous system (CNS)-involvement by underlying disease
- •History of seizure or cerebrovascular ischemia / hemorrhage within the last 12 months
- •History of any autoimmune Central nervous system disease (e.g. multiple sclerosis, amyotrophic lateral sclerosis, optic neuritis)
- •Ongoing neurologic conditions that in the opinion of the investigator might increase the risk for neurotoxicity or impair the assessment of CAR-associated neurotoxicity
- •Inadequate pulmonary function (i.e. need for continuous oxygen support)
- •Patients on hemodialysis
- •Any contraindications to Fludarabine and/or Cyclophosphamide as given in the Summary of product characteristics
- •Any other active malignancy requiring active treatment or interfering with the assessment of primary or secondary trial endpoints, adjuvant hormonal therapy is allowed
- •Positivity for anti-human immunodeficiency virus (HIV) immunoglobulin
- •Active or chronic infectious hepatitis B (HBV) and C (HCV) virus unless serology demonstrates clearance of infection (i.e. Polymerase chain reaction undetectable viral load for hepatitis)
Outcomes
Primary Outcomes
Incidence and severity of adverse events and serious adverse events
Time Frame: appr. 24 months
graded according to Common Terminology Criteria of Adverse Events V5.0
Incidence and severity of Immune effector cell-associated neurotoxicity syndrome
Time Frame: appr. 24 months
Grading of Immune effector cell-associated neurotoxicity syndrome according to American Society for Transplantation and Cellular Therapy consensus criteria
Maximum tolerated dose (MTD) of MDC-CAR-BCMA001
Time Frame: appr. 24 months
The MTD will be defined as the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate.
Incidence and severity of Cytokine release syndrome
Time Frame: appr. 24 months
Grading of Cytokine release syndrome according to American Society for Transplantation and Cellular Therapy consensus criteria
Incidence of dose-limiting toxicity (DLT) during DLT-evaluation period and beyond
Time Frame: appr.24 months