Brief Title
Ph I Trial of NAM NK Cells and IL-2 for Adult Pts With MM and NHL
Official Title
A Phase I Trial Testing NAM Expanded Haploidentical or Mismatched Related Donor Natural Killer (NK) Cells Followed by a Short Course of IL-2 for the Treatment of Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory CD20+ Non-Hodgkin Lymphoma
Brief Summary
This is a phase I trial with pilot expansion of HLA-haploidentical or HLA-mismatched related
donor nicotinamide expanded-natural killer (NAM-NK) cell based therapy for patients with
relapsed or refractory multiple myeloma (MM) or relapsed/refractory CD20-positive non-Hodgkin
lymphoma (NHL). The primary endpoint of the study is to determine the maximum tolerated dose
(MTD) of NAM-NK cells while maintaining safety.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Occurrence of any grade 4 or greater suspected adverse reaction
Secondary Outcome
Occurrence of treatment related mortality (TRM)
Condition
Multiple Myeloma
Intervention
Nicotinamide Expanded Haploidentical or Mismatched Related Donor Natural Killer Cells
Study Arms / Comparison Groups
Multiple Myeloma
Description: After a lymphodepleting preparative regimen of cyclophosphamide and fludarabine, patients receive expanded NAM-NK cells followed by a short course of interleukin-2 (IL-2) to facilitate natural killer cell survival and expansion in vivo. Monoclonal antibodies and elotuzumab for Multiple Myeloma patients, will be administered prior to and after the natural killer cell infusion(s) to facilitate tumor targeting and antibody dependent cellular cytotoxicity (ADCC).
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
39
Start Date
October 18, 2017
Completion Date
August 15, 2022
Primary Completion Date
August 15, 2022
Eligibility Criteria
Patient Inclusion Criteria:
- ≥18 to ≤70 years of age
- Meets one of the following disease criteria:
- Multiple Myeloma (MM) meeting one of the following:
- relapsed/refractory disease after two lines of therapies, including a
proteasome inhibitor (bortezomib, carfilzomib or ixazomib) and an
immunomodulatory drug (thalidomide, lenalidomide or pomalidomide)
- relapsed disease between 2-18 months of 1st autologous stem cell
transplantation,
- relapsed disease at least 4 months after allogeneic stem cell
transplantation with no evidence of active graft versus host disease and no
availability of donor lymphocyte infusion
- measurable disease defined as serum IgG, A, M M-protein ≥ 0.5g/dL or serum
IgD M-protein ≥ 0.5 g/dL, or urine M-protein ≥ 200 mg/24 hours
- at least 4 weeks since plasmapheresis
- at least 3 days between last corticosteroids and study treatment start
- CD20-positive B-cell Non-Hodgkin Lymphoma (NHL)
- CD20 expression confirmed by flow cytometry or immunohistochemistry and
meeting one or more of the following:
- evidence of relapsed/refractory disease that has failed conventional
therapy and failed/not eligible/refused studies of a higher priority,
- relapsed disease at least 60 days after autologous stem cell
transplantation
- relapsed disease at least 4 months after allogeneic stem cell
transplantation with no evidence of active graft versus host disease
and no availability of donor lymphocyte infusion
- has measurable disease >1.5 cm in diameter
- HLA-haploidentical or mismatched related donor (aged 12 to 70 years) with
donor/recipient match based on a minimum of intermediate resolution DNA based Class I
typing of the A and B locus (at least 2/4 class I allele) and absence of recipient
anti HLA antibodies against selected donor
- Karnofsky Performance Status ≥ 60% - appendix III
- Adequate organ function within 14 days of study registration (30 days for pulmonary
and cardiac assessments) defined as:
- Bone Marrow: Total white blood cell (WBC) count ≥ 3000/μL, absolute neutrophil
count (ANC) ≥ 1000/μL, platelet count ≥ 75,000/μL and hemoglobin ≥ 8.0 g/dL - may
be waived if abnormalities are due to disease related bone marrow involvement
- Renal: creatinine ≤ 1.5 mg/dL or creatinine clearance ≥40mL/min using
Cockcroft-Gault formula
- Hepatic: ALT or AST ≤ 3 x upper limit of institutional normal (ULN), total
bilirubin ≤ 1.5 x ULN
- Pulmonary Function: oxygen saturation ≥ 90% on room air. If symptomatic or prior
known impairment, pulmonary function ≥ 50% corrected DLCO and FEV1 is required
- Cardiac Function: LVEF ≥ 40%, no uncontrolled angina, severe uncontrolled
ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or
active conduction system abnormalities
- Calcium (MM only): Corrected calcium < 11.5 mg/dL within 2 weeks prior to
enrollment
- Able to be off prednisone or other immunosuppressive medications for at least 3 days
prior to NAM-NK cell infusion (excluding preparative regimen pre-medications)
- Sexually active females of child bearing potential and males with partners of child
bearing potential must agree to use effective contraception during therapy and for 4
months after completion of therapy
- Must have recovered from acute effects of prior therapy - at least 2 weeks should have
elapsed since the last dose of chemotherapy
- Voluntary written consent
Patient Exclusion Criteria:
- Active, untreated CNS involvement
- Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), or high-grade
lymphomas (Burkittt's lymphoma/Lymphoblastic lymphoma)
- Pregnant or breastfeeding - The agents used in this study include those that fall
under Pregnancy Category D - have known teratogenic potential. For elotuzumab arm:
Women of child bearing potential must have a negative serum or urine pregnancy test
(minimum sensitivity 25 IU/L or equivalent units of HCG) within 14 days of study
treatment start (24 hours prior to the start of elotuzumab)
- Marked baseline prolongation of QT/QTc interval (e.g. demonstration of a QTc interval
greater than 500 milliseconds)
- Class II or greater New York Heart Association Functional Classification criteria
(appendix III) or serious cardiac arrhythmias likely to increase the risk of cardiac
complications of cytokine therapy (e.g. ventricular tachycardia, frequent ventricular
ectopy, or supraventricular tachyarrhythmia requiring chronic therapy)
- Active autoimmune disease requiring immunosuppressive therapy
- History of severe asthma, presently on chronic medications (a history of mild asthma
requiring inhaled steroids only is eligible)
- New or progressive pulmonary infiltrates on screening chest x-ray or chest CT scan
unless cleared for study by Pulmonary. Infiltrates attributed to infection must be
stable/improving (with associated clinical improvement) after 1 week of appropriate
therapy (4 weeks for presumed or documented fungal infections).
- Active uncontrolled bacterial, fungal, or viral infections - all prior infections must
have resolved following optimal therapy
- Known hypersensitivity to any of the study agents used
- For MM patients only:
- Prior radiotherapy within 2 weeks prior to the administration of study drug"
- Surgery within 4 weeks
- Chemo within 3 weeks (6 weeks for melphalan, or monoclonal antibodies)
- Received investigational drugs within the 14 days before 1st dose of study drug
- High titer of donor specific anti-HLA antibodies (MFI >1000)
DONOR INCLUSION CRITERIA:
- HLA-haploidentical or mismatched related donor/recipient match based on a minimum of
intermediate resolution DNA based Class I typing of the A and B locus (at least 2/4
class I allele) and absence of recipient anti HLA antibodies
- 12 to 70 years of age - Priority should be given to age (<35 years), followed by HLA
matching (haploidentical and if not available then fully mismatched donor).
- At least 40 kilogram body weight
- In general good health as determined by the evaluating medical provider
- Adequate organ function defined as:
- Hematologic: hemoglobin, WBC, platelet within 10% of upper and lower limit of
normal range of test (gender based for hemoglobin),
- Hepatic: ALT < 2 x upper limit of normal,
- Renal: serum creatinine < 1.8 mg/dl
- Performance of a donor infectious disease screen panel including CMV Antibody,
Hepatitis B Surface Antigen, Hepatitis B Core Antibody, Hepatitis C Antibody, HIV PCR,
HIV ½ Antibody, HTLVA ½ Antibody, Rapid Plasma (RPR) Treponema , Trypanosoma Cruzi (T.
Cruzi), HCV by NAT, HIV by NAT and WNV (West Nile Virus) by NAT or per current panel -
must be negative for HIV and active hepatitis B
- Not pregnant - females of childbearing potential must have a negative pregnancy test
within 7 days of apheresis
- Able and willing to undergo apheresis
- Voluntary written consent (using assent form if donor < 18 years of age)
Gender
All
Ages
18 Years - 70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Veronika Bachanova, MD, PhD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03019666
Organization ID
2015LS057
Secondary IDs
MT2015-46
Responsible Party
Sponsor
Study Sponsor
Masonic Cancer Center, University of Minnesota
Study Sponsor
Veronika Bachanova, MD, PhD, Principal Investigator, University of Minnesota
Verification Date
November 2022