Plasma Cell Leukemia, Plasma Cell Myeloma
Conditions
Brief summary
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.
Detailed description
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.
Interventions
PROCEDUREAutologous Hematopoietic Stem Cell Transplantation
Undergo autologous stem cell transplant
BIOLOGICALElotuzumab
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGLenalidomide
Given PO
DRUGMelphalan
Given IV
BIOLOGICALNatural Killer Cell Therapy
Given IV
Given IV
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) | Up to 12 months | Number of participants that are alive and disease free one year post transplant |
Countries
United States
Participant flow
Recruitment details
All participants were registered in MD Anderson Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| P1_C1_5x10^6 Patients receive 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.
Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant
Elotuzumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
Melphalan: Given IV
Natural Killer Cell Therapy: Given IV
Umbilical Cord Blood-Derived Lymphocyte Therapy: Given IV | 3 |
| P1_C2_1x10^7 Patients receive 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.
Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant
Elotuzumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
Melphalan: Given IV
Natural Killer Cell Therapy: Given IV
Umbilical Cord Blood-Derived Lymphocyte Therapy: Given IV | 3 |
| P1_C3_5x10^7 Patients receive 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.
Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant
Elotuzumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
Melphalan: Given IV
Natural Killer Cell Therapy: Given IV
Umbilical Cord Blood-Derived Lymphocyte Therapy: Given IV | 4 |
| P1_C4_1X10^8 Patients receive 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.
Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant
Elotuzumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
Melphalan: Given IV
Natural Killer Cell Therapy: Given IV
Umbilical Cord Blood-Derived Lymphocyte Therapy: Given IV | 32 |
| P2_1x10^8+Elotuzumab 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.
Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous stem cell transplant
Elotuzumab: Given IV
Laboratory Biomarker Analysis: Correlative studies
Lenalidomide: Given PO
Melphalan: Given IV
Natural Killer Cell Therapy: Given IV
Umbilical Cord Blood-Derived Lymphocyte Therapy: Given IV | 30 |
| Total | 72 |
Baseline characteristics
| Characteristic | P1_C1_5x10^6 | P1_C2_1x10^7 | P1_C3_5x10^7 | P1_C4_1X10^8 | P2_1x10^8+Elotuzumab | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 1 Participants | 6 Participants | 9 Participants | 19 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 1 Participants | 3 Participants | 26 Participants | 21 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 3 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 3 Participants | 4 Participants | 27 Participants | 27 Participants | 64 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 3 participants | 3 participants | 4 participants | 32 participants | 30 participants | 72 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 1 Participants | 14 Participants | 7 Participants | 24 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 3 Participants | 18 Participants | 23 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 2 / 3 | 2 / 4 | 11 / 32 | 3 / 30 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 4 / 4 | 32 / 32 | 27 / 30 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 0 / 4 | 1 / 32 | 1 / 30 |
Outcome results
Primary
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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| P1_C1_5x10^6 | Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR) | VGPR | 1 Participants |
| P1_C1_5x10^6 | Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR) | CR | 1 Participants |
| P1_C2_1x10^7 | Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR) | VGPR | 0 Participants |
| P1_C2_1x10^7 | Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR) | CR | 3 Participants |
| P1_C3_5x10^7 | Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR) | VGPR | 1 Participants |
| P1_C3_5x10^7 | Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR) | CR | 2 Participants |
| P1_C4_1X10^8 | Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR) | CR | 17 Participants |
| P1_C4_1X10^8 | Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR) | VGPR | 4 Participants |
| P2_1x10^8+Elotuzumab | Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR) | VGPR | 5 Participants |
| P2_1x10^8+Elotuzumab | Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR) | CR | 22 Participants |
Primary
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
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| P1_C1_5x10^6 | Number of Participants With Dose Limiting Toxicities | grade 4 NK infusion related toxicity | 0 Participants |
| P1_C1_5x10^6 | Number of Participants With Dose Limiting Toxicities | failure to engraft by D+28 or delayed engraftment | 0 Participants |
| P1_C1_5x10^6 | Number of Participants With Dose Limiting Toxicities | · grades 3-5 allergic reactions related to study cell infusion | 0 Participants |
| P1_C1_5x10^6 | Number of Participants With Dose Limiting Toxicities | grade 3-5 organ toxicity | 1 Participants |
| P1_C1_5x10^6 | Number of Participants With Dose Limiting Toxicities | grades 3-4 acute GVHD occurring within 45 days post-transplant | 0 Participants |
| P1_C1_5x10^6 | Number of Participants With Dose Limiting Toxicities | treatment-related death within 8 weeks of the study cell infusion | 0 Participants |
| P1_C2_1x10^7 | Number of Participants With Dose Limiting Toxicities | grades 3-4 acute GVHD occurring within 45 days post-transplant | 0 Participants |
| P1_C2_1x10^7 | Number of Participants With Dose Limiting Toxicities | treatment-related death within 8 weeks of the study cell infusion | 0 Participants |
| P1_C2_1x10^7 | Number of Participants With Dose Limiting Toxicities | grade 4 NK infusion related toxicity | 0 Participants |
| P1_C2_1x10^7 | Number of Participants With Dose Limiting Toxicities | · grades 3-5 allergic reactions related to study cell infusion | 0 Participants |
| P1_C2_1x10^7 | Number of Participants With Dose Limiting Toxicities | grade 3-5 organ toxicity | 0 Participants |
| P1_C2_1x10^7 | Number of Participants With Dose Limiting Toxicities | failure to engraft by D+28 or delayed engraftment | 0 Participants |
| P1_C3_5x10^7 | Number of Participants With Dose Limiting Toxicities | grade 3-5 organ toxicity | 0 Participants |
| P1_C3_5x10^7 | Number of Participants With Dose Limiting Toxicities | grades 3-4 acute GVHD occurring within 45 days post-transplant | 0 Participants |
| P1_C3_5x10^7 | Number of Participants With Dose Limiting Toxicities | grade 4 NK infusion related toxicity | 0 Participants |
| P1_C3_5x10^7 | Number of Participants With Dose Limiting Toxicities | · grades 3-5 allergic reactions related to study cell infusion | 0 Participants |
| P1_C3_5x10^7 | Number of Participants With Dose Limiting Toxicities | failure to engraft by D+28 or delayed engraftment | 0 Participants |
| P1_C3_5x10^7 | Number of Participants With Dose Limiting Toxicities | treatment-related death within 8 weeks of the study cell infusion | 0 Participants |
| P1_C4_1X10^8 | Number of Participants With Dose Limiting Toxicities | grade 3-5 organ toxicity | 13 Participants |
| P1_C4_1X10^8 | Number of Participants With Dose Limiting Toxicities | failure to engraft by D+28 or delayed engraftment | 1 Participants |
| P1_C4_1X10^8 | Number of Participants With Dose Limiting Toxicities | · grades 3-5 allergic reactions related to study cell infusion | 0 Participants |
| P1_C4_1X10^8 | Number of Participants With Dose Limiting Toxicities | treatment-related death within 8 weeks of the study cell infusion | 0 Participants |
| P1_C4_1X10^8 | Number of Participants With Dose Limiting Toxicities | grades 3-4 acute GVHD occurring within 45 days post-transplant | 0 Participants |
| P1_C4_1X10^8 | Number of Participants With Dose Limiting Toxicities | grade 4 NK infusion related toxicity | 0 Participants |
| P2_1x10^8+Elotuzumab | Number of Participants With Dose Limiting Toxicities | grades 3-4 acute GVHD occurring within 45 days post-transplant | 0 Participants |
| P2_1x10^8+Elotuzumab | Number of Participants With Dose Limiting Toxicities | · grades 3-5 allergic reactions related to study cell infusion | 0 Participants |
| P2_1x10^8+Elotuzumab | Number of Participants With Dose Limiting Toxicities | failure to engraft by D+28 or delayed engraftment | 0 Participants |
| P2_1x10^8+Elotuzumab | Number of Participants With Dose Limiting Toxicities | treatment-related death within 8 weeks of the study cell infusion | 0 Participants |
| P2_1x10^8+Elotuzumab | Number of Participants With Dose Limiting Toxicities | grade 3-5 organ toxicity | 11 Participants |
| P2_1x10^8+Elotuzumab | Number of Participants With Dose Limiting Toxicities | grade 4 NK infusion related toxicity | 0 Participants |
Secondary
Progression-free Survival (PFS)
Number of participants that are alive and disease free one year post transplant
Time frame: Up to 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| P1_C1_5x10^6 | Progression-free Survival (PFS) | 2 Participants |
| P1_C2_1x10^7 | Progression-free Survival (PFS) | 2 Participants |
| P1_C3_5x10^7 | Progression-free Survival (PFS) | 4 Participants |
| P1_C4_1X10^8 | Progression-free Survival (PFS) | 28 Participants |
| P2_1x10^8+Elotuzumab | Progression-free Survival (PFS) | 28 Participants |