NCT01729091 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2025-05-09

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Dose Limiting Toxicities

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outcome · POSTED

Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR)

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outcome · POSTED

Progression-free Survival (PFS)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
maximum Age: 75 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

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 Names
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
label
Treatment (chemotherapy, UCB-derived NK cells, transplant)
type
EXPERIMENTAL

interventions

arm Group Labels
Treatment (chemotherapy, UCB-derived NK cells, transplant)
description
Undergo autologous stem cell transplant
name
Autologous Hematopoietic Stem Cell Transplantation
other Names
Autologous Hematopoietic Cell Transplantation
autologous stem cell transplantation
type
PROCEDURE
arm Group Labels
Treatment (chemotherapy, UCB-derived NK cells, transplant)
description
Given IV
name
Elotuzumab
other Names
BMS-901608
Empliciti
HuLuc-63
HuLuc63
PDL-063
PDL063
type
BIOLOGICAL
arm Group Labels
Treatment (chemotherapy, UCB-derived NK cells, transplant)
description
Correlative studies
name
Laboratory Biomarker Analysis
type
OTHER
arm Group Labels
Treatment (chemotherapy, UCB-derived NK cells, transplant)
description
Given PO
name
Lenalidomide
other Names
CC-5013
CC5013
CDC 501
Revlimid
type
DRUG
arm Group Labels
Treatment (chemotherapy, UCB-derived NK cells, transplant)
description
Given IV
name
Melphalan
other Names
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
type
DRUG
arm Group Labels
Treatment (chemotherapy, UCB-derived NK cells, transplant)
description
Given IV
name
Natural Killer Cell Therapy
type
BIOLOGICAL
arm Group Labels
Treatment (chemotherapy, UCB-derived NK cells, transplant)
description
Given IV
name
Umbilical Cord Blood-Derived Lymphocyte Therapy
type
BIOLOGICAL

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 72
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Number of Participants With Dose Limiting Toxicities
time Frame
Within 30 days post-transplant
description
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.
measure
Number of Participants That Achieved Very Good Response (VGPR) + Complete Response (CR)
time Frame
At 3 months post-transplant

secondary Outcomes

description
Number of participants that are alive and disease free one year post transplant
measure
Progression-free Survival (PFS)
time Frame
Up to 12 months

Full 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.

Source references