2015-10: Expanded Natural Killer Cells and Elotuzumab for High-Risk Myeloma Post- Autologous Stem Cell Transplant (ASCT)

July 8, 2020 updated by: University of Arkansas

2015-10: A Phase II Pilot Study of Expanded Natural Killer Cells and Elotuzumab to Eradicate High-Risk Myeloma Post Autologous Stem Cell Transplant

This study will evaluate the ability of Expanded Natural Killer (ENK) cells to treat multiple myeloma when administered as part of a regimen consisting of Elotuzumab and a stem cell transplant. Natural killer cells are a special type of white blood cells that are already present in the body which have the ability to kill myeloma cells. In this study, natural killer cells will be collected and then treated in a laboratory to activate and 'expand' the number of cells to increase the dose and the anti-myeloma activity of the cells before they are transfused back into the subject. Elotuzumab is a protein drug approved by the United States Food and Drug Administration (FDA) for patients with previously treated multiple myeloma and works by activating natural killer cells already present in the body and targeting a protein called SLAMF7 which is present on both natural killer cells and myeloma cells. The investigators hope that administering Elotuzumab in combination with ENK cells will enhance the anti-myeloma activity of the ENK cells.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

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
    • Arkansas
      • Little Rock, Arkansas, United States, 72205
        • University of Arkansas for Medical Sciences

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

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Multiple myeloma patients that have completed induction chemotherapy and peripheral blood stem cell collection (PBSC) in preparation for ASCT.
  • Patients must have high-risk disease as defined by Gene Expression Profiling (GEP) 70 risk score of ≥ 0.66 or GEP 80 gene score of ≥ 2.48 or metaphase cytogenetic abnormalities or lactate dehydrogenase (LDH) ≥ 360 U/L (Rule out hemolysis, infection and contact PI for clarification if any doubt).
  • Patients must have failed prior treatment for their multiple myeloma (MM) including a proteasome inhibitor and immunomodulatory drug (so-called 'double refractory'). Patients who have received prior salvage combination chemotherapy after failure of proteasome inhibitor and immunomodulatory drug are eligible (frank relapse at the time of enrollment is not required)
  • Zubrod ≤ 2, unless solely due to symptoms of MM-related (bone) disease.
  • Patients must have a platelet count of ≥ 20,000/μL within 30 days of enrollment, unless lower levels are explained by extensive bone marrow plasmacytosis or extensive prior therapy.
  • Patients must be at least 18 years of age and not older than 75 years of age at the time of registration.
  • must have preserved renal function as defined by a serum creatinine level of ≤ 3 mg/dL within 30 days of registration.
  • Participants must have an ejection fraction by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan ≥ 40% within 90 days prior to registration.
  • Patients must have adequate pulmonary function studies ≥ 50% of predicted on mechanical aspects and diffusion capacity (DLCO) ≥ 50% of predicted within 90 days prior to registration. If the patient is unable to complete pulmonary function tests due to MM-related pain or condition, exception may be granted if the principal investigator documents that the patient is a candidate for high-dose therapy.
  • Patients must have at least 2x106 CD34+ cells/kg stored for transplant. In addition, there will be a 'back-up' available of 2x106 CD34+ cells/kg2x106 CD34+ cells/kg
  • Patients must have signed an Institutional Review Board-approved informed consent and HIPAA authorization form.

Exclusion Criteria:

  • Prior allo-transplant.
  • Prior auto-transplantation is permitted provided the patient is still presently a transplant candidate and at least 2 months should have passed since last auto-transplant
  • History of poorly-controlled hypertension, diabetes mellitus, or any other serious medical illness or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol or could be considered to be an exclusion criterion deemed by the PI.
  • Patients must not have prior malignancy, except for adequately-treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has not received treatment for one year prior to enrollment. Other cancers will only be acceptable if the patient's life expectancy exceeds three years as determined by the PI.
  • Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy test documented within one week of registration. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
  • The subject may not be positive for HIV I/II or HTLV-I/II.

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: Study Treatment
Elotuzumab 10 mg/kg via intravenous infusion on days -16, -3, 12, and 26; Melphalan 200 mg/m2 Ivia intravenous infusion on day -3; ASCT on day -2; ENK infusion on day 0; ALT-803 (Interleukin-15 superagonist) 10 ug/kg via subcutaneous injection on days 1, 8, 15, and 22.
Drug: Elotuzumab
Elotuzumab 10 mg/kg via intravenous infusion on days -16, -3, 12, and 26
Other Names:
  • Empliciti
Drug: Melphalan
Melphalan 200 mg/m2 Ivia intravenous infusion on day -3
Procedure: Autologous Stem Cell Transplant (ASCT)
ASCT on day -2
Biological: Expanded Natural Killer (ENK) Cells
ENK cell infusion on day 0
Drug: ALT-803
ALT-803 (Interleukin-15 superagonist) 10 ug/kg via subcutaneous injection on days 1, 8, 15, and 22
Other Names:
  • IL-15 superagonist

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Multiple Myeloma Response
Time Frame: 98 days post-ENK infusion (100 days post-ASCT)
Response will be measured according to International Myeloma Working Group (IMWG) Criteria
98 days post-ENK infusion (100 days post-ASCT)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse Events
Time Frame: within 98 days post-ENK infusion (100 days post-ASCT)
Frequency and severity of treatment-related adverse events
within 98 days post-ENK infusion (100 days post-ASCT)
Persistence of ENK cells by flow cytometry and/or cytometry by time of flight (CyTOF)
Time Frame: within 98 days post-ENK infusion (100 days post-ASCT)
within 98 days post-ENK infusion (100 days post-ASCT)

Collaborators and Investigators

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

Sponsor

University of Arkansas

Collaborators

Bristol-Myers Squibb
Altor BioScience

Investigators

  • Principal Investigator: Frits van Rhee, MD, PhD, University of Arkansas

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)

November 1, 2019

Primary Completion (Actual)

July 8, 2020

Study Completion (Actual)

July 8, 2020

Study Registration Dates

First Submitted

December 21, 2016

First Submitted That Met QC Criteria

December 21, 2016

First Posted (Estimate)

December 28, 2016

Study Record Updates

Last Update Posted (Actual)

July 10, 2020

Last Update Submitted That Met QC Criteria

July 8, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 205009

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

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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