Clinical Trials /

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

NCT03003728

Description:

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.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 2015-10: Expanded Natural Killer Cells and Elotuzumab for High-Risk Myeloma Post- Autologous Stem Cell Transplant (ASCT)
  • Official Title: 2015-10: A Phase II Pilot Study of Expanded Natural Killer Cells and Elotuzumab to Eradicate High-Risk Myeloma Post Autologous Stem Cell Transplant

Clinical Trial IDs

  • ORG STUDY ID: 205009
  • NCT ID: NCT03003728

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
ElotuzumabEmplicitiStudy Treatment
MelphalanStudy Treatment
Expanded Natural Killer (ENK) CellsStudy Treatment
ALT-803IL-15 superagonistStudy Treatment

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Study TreatmentExperimentalElotuzumab 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.
  • Elotuzumab
  • Melphalan
  • Expanded Natural Killer (ENK) Cells
  • ALT-803

Eligibility Criteria

        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.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:Adverse Events
Time Frame:within 98 days post-ENK infusion (100 days post-ASCT)
Safety Issue:
Description:Frequency and severity of treatment-related adverse events
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Arkansas

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