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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Incidence of dose-limiting toxicities (DLTs)
研究概览
简要总结
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:
- 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
- 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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of multiple myeloma.
- •Renal insufficiency, defined as eGFR < 45 by MDRD formula.
- •At least 18 years of age.
- •ECOG performance status ≤
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Cyclophosphamide (Drug)
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.
干预措施: Ciltacabtagene Autoleucel (Drug)
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.
干预措施: Total body irradiation (Radiation)
结局指标
主要结局
Incidence of dose-limiting toxicities (DLTs)
时间窗: Through 28 days post cilta-cel
Toxicities considered possibly, probably, or definitely related to TBI-based lymphodepletion as graded per CTCAE v 5.0.
次要结局
- Incidence of immune effector cell associated neurotoxicity syndrome (ICANS)(Through day 100)
- Incidence of treatment related adverse events (TEAEs)(Through completion of follow-up (estimated to 1 year and 1 week))
- Incidence of cytokine release syndrome (CRS)(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(1 year post cilta-cel)
- Measurable residual disease (MRD) as measured by ClonoSeq(1 year post cilta-cel)
- Median duration of response (DoR)(Through completion of follow-up (estimated to 1 year and 1 week))
- Duration of response(Through completion of follow-up (estimated to 1 year and 1 week))
- Progression-free survival (PFS)(Through completion of follow-up (estimated to 1 year and 1 week))
- Overall survival (OS)(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(Day 28 post cilta-cel)
- Measurable residual disease (MRD) as measured by ClonoSeq(Day 100 post cilta-cel)
- Response rate by IMWG criteria(Day 28 post cilta-cel)
- Response rate by IMWG criteria(Day 100 post cilta-cel)