Clinical trial NCT03003728: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Multiple Myeloma
Lead sponsor: University of Arkansas
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
name: Altor BioScience
First posted: 2016-12-28
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: Multiple Myeloma Response
timeFrame: 98 days post-ENK infusion (100 days post-ASCT)
Secondary outcomes:
measure: Adverse Events
timeFrame: within 98 days post-ENK infusion (100 days post-ASCT)
measure: Persistence of ENK cells by flow cytometry and/or cytometry by time of flight (CyTOF)
timeFrame: within 98 days post-ENK infusion (100 days post-ASCT)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
Study officials:
affiliation: University of Arkansas
name: Frits van Rhee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: