Using radiation and chemotherapy before CAR T-cell therapy for multiple myeloma patients with kidney issues
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
This study is testing if using low-dose radiation and chemotherapy before CAR T-cell therapy can help people with multiple myeloma and kidney problems get better results.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 16 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Washington University School of Medicine Academic / other |
| Drugs / interventions | CAR T, chemotherapy, cyclophosphamide, fludarabine |
| Locations | 1 site (St Louis, Missouri) |
| Trial ID | NCT06623630 on ClinicalTrials.gov |
What this trial studies
This clinical trial investigates the safety and effectiveness of a lymphodepleting regimen that combines low-dose total body irradiation (TBI) and cyclophosphamide prior to administering cilta-cel, a CAR T-cell therapy, in patients with multiple myeloma who have impaired renal function. The study aims to address the unmet clinical need for effective treatments in this population, which has been largely excluded from previous trials. By evaluating the CAR T-cell expansion and persistence, the trial seeks to determine if this approach can lead to improved disease outcomes for these patients.
Who should consider this trial
Good fit: Ideal candidates for this study are adults aged 18 and older with a confirmed diagnosis of multiple myeloma and renal insufficiency (eGFR < 45).
Not a fit: Patients with prior or concurrent malignancies that could interfere with the study's safety or efficacy assessments may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for multiple myeloma patients with renal insufficiency, potentially improving their outcomes.
How similar studies have performed: While there have been studies on CAR T-cell therapies, this specific approach combining TBI and cyclophosphamide for patients with renal impairment is novel and has not been extensively tested.
Eligibility criteria
Show full inclusion / exclusion 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). * 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.
Where this trial is running
St Louis, Missouri
- Washington University School of Medicine — St Louis, Missouri, United States (Recruiting)
Study contacts
- Principal investigator: Michael J Slade, M.D., MSCI — Washington University School of Medicine
- Study coordinator: Michael J Slade, M.D., MSCI
- Email: sladem@wustl.edu
- Phone: 314-454-8304
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.