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

May 7, 2025 updated by: M.D. Anderson Cancer Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

72

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment (chemotherapy, UCB-derived NK cells, transplant)
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.
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • Revlimid
  • CC5013
  • CDC 501
Drug: Melphalan
Given IV
Other Names:
  • CB-3025
  • L-PAM
  • Alanine Nitrogen Mustard
  • L-Phenylalanine Mustard
  • L-Sarcolysin Phenylalanine mustard
  • L-Sarcolysine
  • Melphalanum
  • Phenylalanine Mustard
  • Sarcoclorin
  • Sarkolysin
  • WR-19813
  • L-sarcolysin
  • Phenylalanine nitrogen mustard
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous stem cell transplant
Other Names:
  • Autologous Hematopoietic Cell Transplantation
  • autologous stem cell transplantation
Biological: Elotuzumab
Given IV
Other Names:
  • BMS-901608
  • Empliciti
  • HuLuc-63
  • HuLuc63
  • PDL-063
  • PDL063
Biological: Natural Killer Cell Therapy
Given IV
Biological: Umbilical Cord Blood-Derived Lymphocyte Therapy
Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Dose Limiting Toxicities
Time Frame: 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.
Within 30 days post-transplant
Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR)
Time Frame: 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.
At 3 months post-transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS)
Time Frame: Up to 12 months
Number of participants that are alive and disease free one year post transplant
Up to 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Samer S Srour, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 10, 2013

Primary Completion (Actual)

June 25, 2024

Study Completion (Actual)

June 25, 2024

Study Registration Dates

First Submitted

November 9, 2012

First Submitted That Met QC Criteria

November 13, 2012

First Posted (Estimated)

November 20, 2012

Study Record Updates

Last Update Posted (Actual)

May 9, 2025

Last Update Submitted That Met QC Criteria

May 7, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011-0379 (Other Identifier: M D Anderson Cancer Center)
  • NCI-2014-01096 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • RV-MM-PI-0691
  • NCI-2014-00541

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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