Lymphodepleting Total Body Irradiation (TBI) Plus Cyclophosphamide Prior to Ciltacabtagene Autoleucel (Carvykti; Cilta-cel) for Multiple Myeloma (MM) Patients With Impaired Renal Function

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

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).

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Ciltacabtagene Autoleucel; Radiation: Total body irradiation

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Michael J Slade, M.D., MSCI; Phone Number: 314-454-8304; Email: sladem@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
      • Sub-Investigator: Zachary Crees, M.D.
      • Sub-Investigator: Feng Gao, Ph.D.
      • Sub-Investigator: Keith Stockerl-Goldstein, M.D.
      • Sub-Investigator: Ravi Vij, M.D.
      • Sub-Investigator: Mark Schroeder, M.D.
      • Contact: Michael J Slade, M.D., MSCI; Phone Number: 314-454-8304; Email: sladem@wustl.edu
      • Principal Investigator: Michael J Slade, M.D., MSCI
      • Sub-Investigator: Nathan Singh, M.D., M.S.
      • Sub-Investigator: Miriam Y Kim, M.D.
      • Sub-Investigator: Joanna C Yang, M.D., M.P.H.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).
• ANC ≥ 1.0 k/cumm. If neutropenia is present at initial screening but is judged to be attributable to bridging and/or leading therapies, patients can be re-tested within the screening period to confirm eligibility.
• Patients with a history of prior autologous hematopoietic cell transplant (AHCT) must have received a graft containing ≥2.0 x 106 CD34+ cells/kg body weight.
• Availability of adequate cryopreserved autologous stem cells (≥2.0 x 106 CD34+ cells/kg body weight) to allow for an autologous stem cell boost in case of prolonged cytopenias.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cyclophosphamide + Cilta-Cel + TBI; All patients will undergo T-cell collection and CAR T manufacturing as per standard of care. Patients will receive cyclophosphamide per standard of care Day -5 to Day -3. They will subsequently receive TBI on Day -1 then and will receive cilta-cel infusion on Day 0.	Drug: Cyclophosphamide; Standard of care; Drug: Ciltacabtagene Autoleucel; Standard of care; Other Names: Carvykti; cilta-cel; Radiation: Total body irradiation; Radiation doses delivered to the entire body; Other Names: TBI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose-limiting toxicities (DLTs)	Toxicities considered possibly, probably, or definitely related to TBI-based lymphodepletion as graded per CTCAE v 5.0.	Through 28 days post cilta-cel

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment related adverse events (TEAEs)	Graded per CTCAE v 5.0.; All AEs will be collected from start of treatment through Day 28. After Day 28, only late toxicities of interest will be tracked and recorded.	Through completion of follow-up (estimated to 1 year and 1 week)
Incidence of cytokine release syndrome (CRS)		Through day 100
Incidence of immune effector cell associated neurotoxicity syndrome (ICANS)	Graded per ASTCT criteria	Through day 100
Best overall response by IMWG criteria		Through completion of follow-up (estimated to 1 year and 1 week)
Response rate by IMWG criteria		Day 28 post cilta-cel
Response rate by IMWG criteria		Day 100 post cilta-cel
Response rate by IMWG criteria		1 year post cilta-cel
Measurable residual disease (MRD) as measured by ClonoSeq		Day 28 post cilta-cel
Measurable residual disease (MRD) as measured by ClonoSeq		Day 100 post cilta-cel
Median duration of response (DoR)	Duration of response (DoR) is defined as the time from onset of response to progression or death due to any reason, whichever occurs earlier.	Through completion of follow-up (estimated to 1 year and 1 week)
Duration of response	Duration of response (DoR) is defined as the time from onset of response to progression or death due to any reason, whichever occurs earlier.	Through completion of follow-up (estimated to 1 year and 1 week)
Progression-free survival (PFS)	Progression-free survival (PFS) is defined as the time from start of treatment (Day 0) until date of disease progression.	Through completion of follow-up (estimated to 1 year and 1 week)
Overall survival (OS)	Overall survival (OS) is defined as the time from start of treatment (Day 0) until date of death.	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.		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).		Through completion of follow-up (estimated to 1 year and 1 week)
Measurable residual disease (MRD) as measured by ClonoSeq		1 year post cilta-cel

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: American Cancer Society, Inc.; Cures Within Reach
• Investigators: Principal Investigator: Michael J Slade, M.D., MSCI, Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: September 30, 2024
• First Submitted That Met QC Criteria: September 30, 2024
• First Posted (Actual): October 2, 2024

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 8, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Renal failure; Radiation; Chimeric antigen receptor T cells
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Renal Insufficiency; Organic Chemicals; Investigative Techniques; Therapeutics; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Radiotherapy; Cyclophosphamide; Whole-Body Irradiation
• Other Study ID Numbers: 202410010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No