Recruiting
Phase 1

TBI & Cyclophosphamide

Sponsor:

Washington University School of Medicine

Code:

NCT06623630

Conditions

Multiple Myeloma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Cyclophosphamide

Ciltacabtagene Autoleucel

Total body irradiation

Study Details

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).

Conditions

Multiple Myeloma

Study ID

NCT06623630

Start date

Dec 4, 2024

Status verified date

Mar, 2026

Completion date

May 31, 2028

Anticipated

Primary completion date

Jun 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

16 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

Interventions

Cyclophosphamide

Standard of care

Ciltacabtagene Autoleucel

Standard of care

Total body irradiation

Radiation doses delivered to the entire body

Primary outcome measure

  • Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Through 28 days post cilta-cel ]

Central Contacts and Locations

Central contacts

Michael J Slade, M.D., MSCI

314-454-8304sladem@wustl.edu

Locations

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63110

Contacts

Michael J Slade, M.D., MSCI

314-454-8304sladem@wustl.edu

Principal Investigator:

Michael J Slade, M.D., MSCI

More Information

Sponsor

Washington University School of Medicine

Last update posted

Mar 11, 2026

Last verified

Mar, 2026

Keywords

  • Chimeric antigen receptor T cells
  • Radiation
  • Immunotherapy
  • Renal failure

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Washington University School of Medicine on 2026-03-11.