Umbilical Cord Blood-Derived Natural Killer Cells, Elotuzumab, Lenalidomide, and High Dose Melphalan, Followed by Stem Cell Transplant in Treating Patients With Multiple Myeloma
Primary Purpose
Plasma Cell Leukemia, Plasma Cell Myeloma
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Autologous Hematopoietic Stem Cell Transplantation
Elotuzumab
Laboratory Biomarker Analysis
Lenalidomide
Melphalan
Natural Killer Cell Therapy
Umbilical Cord Blood-Derived Lymphocyte Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Plasma Cell Leukemia
Eligibility Criteria
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
Sites / Locations
- M D Anderson Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (chemotherapy, UCB-derived NK cells, transplant)
Arm Description
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.
Outcomes
Primary Outcome Measures
Maximum tolerated dose of umbilical cord blood (UCB)-derived natural killer (NK) cells
Defined as the highest dose for which the probability of toxicity is closest to 20%. Logistic regression methods will be used to model the rate of dose-limiting toxicity as a function of potential prognostic factors (such as demographics, International Staging System stage, and cytogenetic abnormalities).
Percent of patients achieving very good partial response (VGPR) + complete response (CR)
Response will be tabulated by dose. Logistic regression methods will be used to model the rate of VGPR + CR as a function of potential prognostic factors (such as demographics, International Staging System stage, and cytogenetic abnormalities). Will estimate with a 95 percent credible interval.
Minimal residual disease (MRD) rate
Will model the MRD rate in high-risk patients using logistical regression.
Overall survival (OS)
OS will be estimated using the Kaplan-Meier product limit estimator, and Cox proportional hazards regression will be used to model OS as functions of the potential prognostic factors. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Progression-free survival (PFS)
PFS will be estimated using the Kaplan-Meier product limit estimator, and Cox proportional hazards regression will be used to model PFS as functions of the potential prognostic factors. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Secondary Outcome Measures
Duration of infused umbilical cord blood (UCB)-natural killer (NK) cells in new host
Will be reported as an average time value with standard deviation. These data may also be used as covariates in the regression models.
Full Information
NCT ID
NCT01729091
First Posted
November 9, 2012
Last Updated
June 20, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT01729091
Brief Title
Umbilical Cord Blood-Derived Natural Killer Cells, Elotuzumab, Lenalidomide, and High Dose Melphalan, Followed by Stem Cell Transplant in Treating Patients With Multiple Myeloma
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 10, 2013 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plasma Cell Leukemia, Plasma Cell Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
72 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment (chemotherapy, UCB-derived NK cells, transplant)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Autologous Hematopoietic Stem Cell Transplantation
Other Intervention Name(s)
Autologous Hematopoietic Cell Transplantation, autologous stem cell transplantation
Intervention Description
Undergo autologous stem cell transplant
Intervention Type
Biological
Intervention Name(s)
Elotuzumab
Other Intervention Name(s)
BMS-901608, Empliciti, HuLuc-63, HuLuc63, PDL-063, PDL063
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
CC-5013, CC5013, CDC 501, Revlimid
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine nitrogen mustard, Sarcoclorin, Sarkolysin, WR-19813
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Natural Killer Cell Therapy
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Umbilical Cord Blood-Derived Lymphocyte Therapy
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Maximum tolerated dose of umbilical cord blood (UCB)-derived natural killer (NK) cells
Description
Defined as the highest dose for which the probability of toxicity is closest to 20%. Logistic regression methods will be used to model the rate of dose-limiting toxicity as a function of potential prognostic factors (such as demographics, International Staging System stage, and cytogenetic abnormalities).
Time Frame
Within 30 days post-transplant
Title
Percent of patients achieving very good partial response (VGPR) + complete response (CR)
Description
Response will be tabulated by dose. Logistic regression methods will be used to model the rate of VGPR + CR as a function of potential prognostic factors (such as demographics, International Staging System stage, and cytogenetic abnormalities). Will estimate with a 95 percent credible interval.
Time Frame
At 3 months post-transplant
Title
Minimal residual disease (MRD) rate
Description
Will model the MRD rate in high-risk patients using logistical regression.
Time Frame
At 100 days
Title
Overall survival (OS)
Description
OS will be estimated using the Kaplan-Meier product limit estimator, and Cox proportional hazards regression will be used to model OS as functions of the potential prognostic factors. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Time Frame
Up to 12 months
Title
Progression-free survival (PFS)
Description
PFS will be estimated using the Kaplan-Meier product limit estimator, and Cox proportional hazards regression will be used to model PFS as functions of the potential prognostic factors. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Duration of infused umbilical cord blood (UCB)-natural killer (NK) cells in new host
Description
Will be reported as an average time value with standard deviation. These data may also be used as covariates in the regression models.
Time Frame
Up to 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Samer S Srour
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center Website
Learn more about this trial
Umbilical Cord Blood-Derived Natural Killer Cells, Elotuzumab, Lenalidomide, and High Dose Melphalan, Followed by Stem Cell Transplant in Treating Patients With Multiple Myeloma
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