Phase II Study of Umbilical Cord Blood-Derived Natural Killer Cells in Conjunction With Elotuzumab, Lenalidomide and High Dose Melphalan Followed by Autologous Stem Cell Transplant for Patients With Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Number of Participants With Dose Limiting Toxicities
研究概览
简要总结
This phase II trial studies the side effects and best dose of umbilical cord blood-derived natural killer cells when given together with elotuzumab, lenalidomide, and high dose melphalan before autologous stem cell transplant and to see how well they work in treating patients with multiple myeloma. Before transplant, stem cells are taken from patients and stored. Immunotherapy with monoclonal antibodies, such as elotuzumab, may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide and melphalan, may work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy before a stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving natural killer cells from donor umbilical cord blood before transplant may also kill myeloma cells that remain in the body after the last chemotherapy treatment. After treatment, stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.
详细描述
PRIMARY OBJECTIVES:
I. To find the maximum tolerated dose (MTD) of umbilical cord blood (UCB)-derived natural killer (NK) cells.
II. To determine efficacy by the percent of patients achieving very good partial remission (VGPR) + complete remission (CR) at 3 months post-transplant.
III. To assess the minimal residual disease rate 100 days post-transplant in high-risk patients.
SECONDARY OBJECTIVE:
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with high risk multiple myeloma who are transplant candidates, in partial response (PR) or better; high risk will be defined as patients with any of the following:
- •Fluorescence in situ hybridization showing t(4:14), t(14:16), t(14:20), gain (amp) 1q; deletion (Del) 17/17p [or tp53 gene mutation/deletion by next generation sequencing (NGS), or by conventional cytogenetics];
- •Deletion 13 by conventional cytogenetic analysis;
- •High risk signatures as determined by the GEP-70 or EMC-92 gene expression profiles;
- •Relapsed disease within 18 months of prior autologous stem cell transplant (ASCT)
- •Patients with plasma cell leukemia who are transplant candidates
- •Performance score of at least 70% by Karnofsky or 0 to 2 Eastern Cooperative Oncology Group (ECOG)
- •Left ventricular ejection fraction greater than 40%
- •Pulmonary function test (PFT) demonstrating a diffusion capacity of least 40% predicted
- •Estimated serum creatinine clearance >= 60 ml/min (using the Cockcroft-Gault formula and/or serum creatinine =< 1.6 mg/dL
- •Serum glutamate pyruvate transaminase (SGPT) less than 3 x upper limit of normal
- •Total bilirubin less than 2 x upper limit of normal
- •All study participants must be registered into the mandatory Revlimid Risk Evaluation and Mitigation Strategy (REMS) program, and be willing and able to comply with the requirements of the Revlimid REMS program
- •Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS program
- •Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy
- •Patients must have a cord blood (CB) unit available which is matched with the patient at 4, 5, or 6/6 human leukocyte antigen (HLA) class I (serological) and II (molecular) antigens
- •Patient or legally authorized representative able to sign informed consent
排除标准
- •Patients receiving any other investigational agents
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to melphalan
- •Known hypersensitivity or desquamating rash to either thalidomide or lenalidomide
- •Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, uncontrolled hypertension (systolic > 160, diastolic > 100 despite antihypertensive therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- •Human immunodeficiency virus (HIV)-positive patients are excluded due to increased risk of lethal infections when treated with myeloablative chemotherapy
研究组 & 干预措施
Treatment (chemotherapy, UCB-derived NK cells, transplant)
Patients receive elotuzumab IV over 2-5 hours on day -15 and -8, lenalidomide PO QD on days -8 to -2, high-dose melphalan IV over 30 minutes on day -7, and UCB-derived NK cells IV over 1 hour on day -5. Patients undergo autologous stem cell transplant on day 0.
干预措施: Autologous Hematopoietic Stem Cell Transplantation (Procedure)
Treatment (chemotherapy, UCB-derived NK cells, transplant)
Patients receive elotuzumab IV over 2-5 hours on day -15 and -8, lenalidomide PO QD on days -8 to -2, high-dose melphalan IV over 30 minutes on day -7, and UCB-derived NK cells IV over 1 hour on day -5. Patients undergo autologous stem cell transplant on day 0.
干预措施: Elotuzumab (Biological)
Treatment (chemotherapy, UCB-derived NK cells, transplant)
Patients receive elotuzumab IV over 2-5 hours on day -15 and -8, lenalidomide PO QD on days -8 to -2, high-dose melphalan IV over 30 minutes on day -7, and UCB-derived NK cells IV over 1 hour on day -5. Patients undergo autologous stem cell transplant on day 0.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (chemotherapy, UCB-derived NK cells, transplant)
Patients receive elotuzumab IV over 2-5 hours on day -15 and -8, lenalidomide PO QD on days -8 to -2, high-dose melphalan IV over 30 minutes on day -7, and UCB-derived NK cells IV over 1 hour on day -5. Patients undergo autologous stem cell transplant on day 0.
干预措施: Lenalidomide (Drug)
Treatment (chemotherapy, UCB-derived NK cells, transplant)
Patients receive elotuzumab IV over 2-5 hours on day -15 and -8, lenalidomide PO QD on days -8 to -2, high-dose melphalan IV over 30 minutes on day -7, and UCB-derived NK cells IV over 1 hour on day -5. Patients undergo autologous stem cell transplant on day 0.
干预措施: Melphalan (Drug)
Treatment (chemotherapy, UCB-derived NK cells, transplant)
Patients receive elotuzumab IV over 2-5 hours on day -15 and -8, lenalidomide PO QD on days -8 to -2, high-dose melphalan IV over 30 minutes on day -7, and UCB-derived NK cells IV over 1 hour on day -5. Patients undergo autologous stem cell transplant on day 0.
干预措施: Natural Killer Cell Therapy (Biological)
Treatment (chemotherapy, UCB-derived NK cells, transplant)
Patients receive elotuzumab IV over 2-5 hours on day -15 and -8, lenalidomide PO QD on days -8 to -2, high-dose melphalan IV over 30 minutes on day -7, and UCB-derived NK cells IV over 1 hour on day -5. Patients undergo autologous stem cell transplant on day 0.
干预措施: Umbilical Cord Blood-Derived Lymphocyte Therapy (Biological)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities
时间窗: Within 30 days post-transplant
Dose limiting toxicity is defined as number of participants experienced: * grade 4 NK infusion related toxicity, * failure to engraft by D+28 or delayed engraftment, * grades 3-5 allergic reactions related to study cell infusion, * grade 3-5 organ toxicity (cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic) not pre-existing or due to the underlying malignancy or due to preparative chemotherapy and occurring within 30 days (+3 days if necessary) post-transplant, * grades 3-4 acute GVHD occurring within 45 days post-transplant, * treatment-related death within 8 weeks of the study cell infusion.
Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR)
时间窗: At 3 months post-transplant
Complete response (CR) (all of the following): 1. Negative immunofixation in serum and urine. 2. \< 5% plasma cells in the bone marrow. 3. Disappearance of any soft tissue plasmacytomas. Very good partial response (VGPR) (one of the following): 1. Serum and urine M protein detectable by immunofixation but not by electrophoresis. 2. 90% or greater reduction in serum M protein plus urine M protein level \<100 mg per 4h.
次要结局
- Progression-free Survival (PFS)(Up to 12 months)