Umbilical Cord Blood-Derived Natural Killer Cells, Elotuzumab, Lenalidomide, and High Dose Melphalan, Followed by Stem Cell Transplant in Treating Patients With Multiple Myeloma

Plasma Cell Myeloma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01729091
• Other study ID #: 2011-0379
• Secondary ID: NCI-2014-01096RV
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 10, 2013
• Est. completion date: June 30, 2025

Study information

• Verified date: April 2024
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 72
• Est. completion date: June 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia, Plasma Cell
• Multiple Myeloma
• Neoplasms, Plasma Cell
• Plasma Cell Leukemia
• Plasma Cell Myeloma

Intervention

Procedure:
• Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous stem cell transplant

Biological:
• Elotuzumab
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Lenalidomide
Given PO
• Melphalan
Given IV

Biological:
• Natural Killer Cell Therapy
Given IV
• Umbilical Cord Blood-Derived Lymphocyte Therapy
Given IV

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Within 30 days post-transplant
Primary	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.	At 3 months post-transplant
Primary	Minimal residual disease (MRD) rate	Will model the MRD rate in high-risk patients using logistical regression.	At 100 days
Primary	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.	Up to 12 months
Primary	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.	Up to 12 months
Secondary	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.	Up to 12 months

External Links

•   MD Anderson Cancer Center Website