Clinical trial NCT06623630: Lymphodepleting Total Body Irradiation (TBI) Plus Cyclophosphamide Prior to Ciltacabtagene Autoleucel (Carvykti; Cilta-cel) for Multiple Myeloma (MM) Patients With Impaired Renal Function
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: Chimeric antigen receptor T cells
Radiation
Immunotherapy
Renal failure
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: American Cancer Society, Inc.
name: Cures Within Reach
First posted: 2024-10-02
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed diagnosis of multiple myeloma.
* Renal insufficiency, defined as eGFR \< 45 by MDRD formula.
* At least 18 years of age.
* ECOG performance status ≤ 1.
* Meets standard of care indication for cilta-cel (per FDA approval).
* Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
* Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

Exclusion Criteria:

* Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
* Currently receiving any other investigational agents.
* Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or unstable cardiac arrhythmia. Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Function Classification; to be eligible for this trial, patients should be a class 2B or better.
* Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
* HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible.
* Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible.
* History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible.

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs)
timeFrame: Through 28 days post cilta-cel
Secondary outcomes:
measure: Incidence of treatment related adverse events (TEAEs)
timeFrame: Through completion of follow-up (estimated to 1 year and 1 week)
measure: Incidence of cytokine release syndrome (CRS)
timeFrame: Through day 100
measure: Incidence of immune effector cell associated neurotoxicity syndrome (ICANS)
timeFrame: Through day 100
measure: Best overall response by IMWG criteria
timeFrame: Through completion of follow-up (estimated to 1 year and 1 week)
measure: Response rate by IMWG criteria
timeFrame: Day 28 post cilta-cel
measure: Response rate by IMWG criteria
timeFrame: Day 100 post cilta-cel
measure: Response rate by IMWG criteria
timeFrame: 1 year post cilta-cel
measure: Measurable residual disease (MRD) as measured by ClonoSeq
timeFrame: Day 28 post cilta-cel
measure: Measurable residual disease (MRD) as measured by ClonoSeq
timeFrame: Day 100 post cilta-cel
measure: Measurable residual disease (MRD) as measured by ClonoSeq
timeFrame: 1 year post cilta-cel
measure: Median duration of response (DoR)
timeFrame: Through completion of follow-up (estimated to 1 year and 1 week)
measure: Duration of response
timeFrame: Through completion of follow-up (estimated to 1 year and 1 week)
measure: Progression-free survival (PFS)
timeFrame: Through completion of follow-up (estimated to 1 year and 1 week)
measure: Overall survival (OS)
timeFrame: Through completion of follow-up (estimated to 1 year and 1 week)
measure: Area under the curve (AUC) for CAR T expansion as measured by multiparameter flow cytometry.
timeFrame: Through completion of follow-up (estimated to 1 year and 1 week)
measure: Area under the curve (AUC) for CAR T expansion as measured by quantitative polymerase chain reaction (qPCR).
timeFrame: Through completion of follow-up (estimated to 1 year and 1 week)
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Michael J Slade, M.D., MSCI
role: PRINCIPAL_INVESTIGATOR
References: