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.
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: I. To quantify duration of infused allogeneic donor UCB-derived NK cells in the recipient. OUTLINE: This is a dose-escalation study of UCB-derived NK cells. Patients receive elotuzumab intravenously (IV) over 2-5 hours on day -15 and -8, lenalidomide orally (PO) once daily (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. After completion of study treatment, patients are followed up at 30, 60 and 100 days and 6 and 12 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
72
Undergo autologous stem cell transplant
Given IV
Correlative studies
Given PO
Given IV
Given IV
Given IV
M D Anderson Cancer Center
Houston, Texas, United States
Number of Participants With Dose Limiting Toxicities
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.
Time frame: Within 30 days post-transplant
Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR)
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.
Time frame: At 3 months post-transplant
Progression-free Survival (PFS)
Number of participants that are alive and disease free one year post transplant
Time frame: Up to 12 months
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