A Pilot Safety and Feasibility Study of Lymphodepleting Total Body Irradiation (TBI) Plus Cyclophosphamide Prior to Ciltacabtagene Autoleucel (Carvykti; Cilta-cel) for Multiple Myeloma (MM) Patients With Impaired Renal Function
Summary
Treatment for relapsed/refractory multiple myeloma continues to evolve with the approval of highly effective anti-BCMA CAR T therapies in recent years. However, despite the high prevalence of renal insufficiency in this population, pivotal clinical trials have excluded patients with impaired renal function, leading to an urgent, unmet clinical need to develop safe and effective lymphodepleting regimens prior to CAR T administration for this population. In addition, renal insufficiency is linked to poor disease-related outcomes and is highly associated with several underserved populations. This study is testing the hypotheses that: 1. low-dose total body irradiation (TBI) in combination with cyclophosphamide (Cy) as lymphodepletion prior to administration of cilta-cel will be safe and tolerable in patients with multiple myeloma who have impaired renal function 2. low-dose TBI-Cy as lymphodepletion prior to cilta-cel will result in comparable CAR T expansion/persistence and disease response rates as those seen with standard lymphodepleting chemotherapy (fludarabine / cyclophosphamide).
Arms & interventions
- DrugCyclophosphamide
Standard of care
- DrugCiltacabtagene Autoleucel
Standard of care
- RadiationTotal body irradiation
Radiation doses delivered to the entire body
Outcome measures
Primary
Incidence of dose-limiting toxicities (DLTs)
Toxicities considered possibly, probably, or definitely related to TBI-based lymphodepletion as graded per CTCAE v 5.0.
Time frame: Through 28 days post cilta-cel
Secondary
Incidence of treatment related adverse events (TEAEs)
Time frame: Through completion of follow-up (estimated to 1 year and 1 week)
Incidence of cytokine release syndrome (CRS)
Time frame: Through day 100
Incidence of immune effector cell associated neurotoxicity syndrome (ICANS)
Time frame: Through day 100
Best overall response by IMWG criteria
Time frame: Through completion of follow-up (estimated to 1 year and 1 week)
Response rate by IMWG criteria
Time frame: Day 28 post cilta-cel
Response rate by IMWG criteria
Time frame: Day 100 post cilta-cel
Response rate by IMWG criteria
Time frame: 1 year post cilta-cel
Measurable residual disease (MRD) as measured by ClonoSeq
Time frame: Day 28 post cilta-cel
Measurable residual disease (MRD) as measured by ClonoSeq
Time frame: Day 100 post cilta-cel
Measurable residual disease (MRD) as measured by ClonoSeq
Time frame: 1 year post cilta-cel
Median duration of response (DoR)
Time frame: Through completion of follow-up (estimated to 1 year and 1 week)
Duration of response
Time frame: Through completion of follow-up (estimated to 1 year and 1 week)
Progression-free survival (PFS)
Time frame: Through completion of follow-up (estimated to 1 year and 1 week)
Overall survival (OS)
Time frame: Through completion of follow-up (estimated to 1 year and 1 week)
Area under the curve (AUC) for CAR T expansion as measured by multiparameter flow cytometry.
Time frame: Through completion of follow-up (estimated to 1 year and 1 week)
Area under the curve (AUC) for CAR T expansion as measured by quantitative polymerase chain reaction (qPCR).
Time frame: Through completion of follow-up (estimated to 1 year and 1 week)
Eligibility criteria
Study locations (1)
Washington University School of Medicine
St Louis, Missouri, 63110