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

NCT01729091 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: 2011-0379NCI-2014-01096RV-MM-PI-0691NCI-2014-00541
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

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.

Conditions

Plasma Cell Leukemia; Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  At 3 months post-transplant

Secondary Outcomes (1)

• Progression-free Survival (PFS)

  Up to 12 months

Study Arms (1)

Treatment (chemotherapy, UCB-derived NK cells, transplant)

EXPERIMENTAL

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.

Procedure: Autologous Hematopoietic Stem Cell Transplantation; Biological: Elotuzumab; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Drug: Melphalan; Biological: Natural Killer Cell Therapy; Biological: Umbilical Cord Blood-Derived Lymphocyte Therapy

Interventions

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous stem cell transplant

Also known as: Autologous Hematopoietic Cell Transplantation, autologous stem cell transplantation

Treatment (chemotherapy, UCB-derived NK cells, transplant)

Elotuzumab BIOLOGICAL

Given IV

Also known as: BMS-901608, Empliciti, HuLuc-63, HuLuc63, PDL-063, PDL063

Treatment (chemotherapy, UCB-derived NK cells, transplant)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (chemotherapy, UCB-derived NK cells, transplant)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Treatment (chemotherapy, UCB-derived NK cells, transplant)

Melphalan DRUG

Given IV

Also known as: 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

Treatment (chemotherapy, UCB-derived NK cells, transplant)

Natural Killer Cell Therapy BIOLOGICAL

Given IV

Treatment (chemotherapy, UCB-derived NK cells, transplant)

Umbilical Cord Blood-Derived Lymphocyte Therapy BIOLOGICAL

Given IV

Treatment (chemotherapy, UCB-derived NK cells, transplant)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia, Plasma Cell; Multiple Myeloma

Interventions

elotuzumab; Lenalidomide; Melphalan

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Plasma Cell; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Samer Srour, MD / Stem Cell Transplantation
• Organization: The University of Texas MD Anderson Cancer Center

SSrour@mdanderson.org

713-794-4354

Study Officials

• Samer S Srour

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2012
• First Posted: November 20, 2012
• Study Start: June 10, 2013
• Primary Completion: June 25, 2024
• Study Completion: June 25, 2024
• Last Updated: May 9, 2025
• Results First Posted: May 9, 2025

Record last verified: 2025-05

Locations

US (1)