Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE1
35 participants
INTERVENTIONAL
2008-08-01
2021-04-06
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
* What dose of NK cells can be given safely to subjects with metastatic solid tumors or leukemia.
* The effectiveness and side effects of NK cell therapy
* How the body handles NK cells.
People between 18 and 70 years of age who have a solid tumor or leukemia, and for whom standard treatments are not effective, may be eligible for this study. Participants undergo the following procedures:
Apheresis to collect NK cells. For this procedure, a catheter (plastic tube) is placed in a vein in the subject s arm. Blood flows from the vein into a cell separator machine, which separates the white cells from the other blood components. The white cells are extracted and the rest of the blood is returned to the body through a second tube placed in a vein in the other arm.
Chemotherapy with the drug pentostatin to suppress the immune system and prevent it from attacking the NK cells that will be infused.
Chemotherapy with bortezomib to increase NK cell function.
Infusion of the NK cells. In this dose-escalating study, successive groups of patients entering the study receive increasingly higher numbers of cells to determine the highest safe dose level. Up to ten dose levels may be studied.
Interleukin-2 drug therapy to maintain NK cell activity.
Evaluations during therapy including:
* Clinical assessment, history and review of medications
* Blood draws for routine and research tests.
* Pharmacokinetics study after the NK infusion to see how the body handles the cells. For this test, the number of NK cells in the blood are measured over time. This requires drawing about 1 teaspoon of blood at 15 minutes, 30 minutes, 1, 2, 4, 8, 12, and 24 hours after the infusion (day 1); then every 24 hours on days 2 through 7, then once on days 10, 14, and 21.
* Bone marrow biopsy (subjects with leukemia only).
* Chest x-ray.
* CT scan, bone scan and PET scan, if indicated, for disease evaluation.
Subjects who respond well after one treatment cycle may be eligible to continue NK cell therapy.
...
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Murine studies conducted in our laboratory have also established that bortezomib treatment sensitizes tumors in vivo to killing by adoptively infused syngeneic NK cells; murine renal cell carcinoma line (RENCA) tumors in BALB/c mice grew significantly slower and survival was prolonged when syngeneic NK cell infusions where given following bortezomib treatment compared to mice receiving NK cell infusions alone or bortezomib alone. This anti-tumor effect was further potentiated by eradicating T-regulatory cells prior to adoptive NK cell infusion and by administering interleukin-2 after adoptive NK cell infusion.
Recently, our laboratory has developed techniques for the in vitro isolation and expansion of NK cells to levels suitable for the treatment of cancer patients. Furthermore, we have also established good viability and sterility of these expanded NK cells which, compared to fresh NK cells, have increased surface expression of TRAIL and have enhanced cytotoxicity against tumor cells.
We therefore propose this non-randomized, Phase I, dose escalating study designed to evaluate the safety and the anti- tumor effects of escalating doses of adoptively infused ex vivo expanded autologous natural killer (NK) cells against metastatic cancers or hematological malignancies sensitized to NK TRAIL cytotoxicity with bortezomib.
The primary study objective is to determine the safety (maximum tolerated dose) of escalating NK cell doses of adoptively infused ex vivo expanded autologous NK cells in subjects with treatment refractory metastatic tumors or hematological malignancies that are sensitized to NK cell cytotoxicity using bortezomib. Secondary objectives will include the anti-neoplastic effects of this treatment regimen (assessed using standard disease specific response criteria) and the toxicity profile associated with extended cycles of protocol therapy.
The primary endpoint will be assessed at day 21 (3 weeks after the Day 0 NK cell infusion).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
1
NK Cell Infusion (cell /kg pt wt)
NK cells
NK Cell Infusion
2
1.3 mg/m2/dose administered as a 3 to 5 second bolusintravenous injection
Bortezomib
Parenteral formulation. It is supplied as a 3.5 mg single use vial containing a sterile lyophilized powder that requires reconstitution.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Bortezomib
Parenteral formulation. It is supplied as a 3.5 mg single use vial containing a sterile lyophilized powder that requires reconstitution.
NK cells
NK Cell Infusion
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
OR
Diagnosed with a hematological malignancy (multiple myeloma, \[MM\] chronic myelogenous leukemia \[CML\] or chronic lymphocytic leukemia \[CLL\] or small lymphocytic lymphoma \[SLL\]) and disease resistant or refractory to standard therapy and CLL/SLL patients are required to have failed prior treatment with at least one nucleoside analogue. Myeloma patients are required to have disease which has progressed following treatment with bortezomib.
2. At least 4 weeks since any prior systemic therapy (excluding corticosteroid therapy) to treat the underlying malignancy (standard or investigational). NOTE: subjects on FDA-approved tyrosine kinase inhibitors or other targeted therapies for RCC such as mTOR inhibitors that have evidence of disease progression on therapy may continue these medicines until the time of study enrollment (as accelerated disease progression following discontinuation of these drugs has been described).
3. At least 2 weeks since prior palliative radiotherapy.
4. Ages greater than or equal to 18 years and less than or equal to 70 years.
5. Evidence of progressive disease over a 3-month interval.
6. RBC transfusion independent (solid tumor patients only).
Exclusion Criteria
2. Disease involving greater than 25% of the liver radiographically (estimated based on review of liver lesions seen on CT scan).
3. History of an allogeneic hematopoietic stem cell transplant.
4. Brain metastases (with the exception of patients with a single brain metastasis less than 1cm treated with either sterotactic or gamma knife radiotherapy) due to poor prognosis and potential for neurological dysfunction that would confound evaluation of neurological and other adverse events).
5. Peripheral neuropathy of grade greater than 1, which would require reduction of bortezomib dose.
6. Acute diffuse infiltrative pulmonary disease.
7. Acute pericardial disease.
8. Life expectancy less than 3 months.
9. ECOG performance status 2, 3 or 4.
10. Uncontrolled concurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, life threatening cardiac arrhythmia. Patients with symptoms of coronary artery disease, cardiac arrhythmias or an abnormal thallium stress test must be evaluated and cleared by cardiology prior to enrollment.
11. Ongoing or active infection
12. Contraindication for administration of pentostatin, bortezomib, and/or interleukin-2.
13. Allergy or hypersensitivity to bortezomib, boron or mannitol by history.
14. Concurrent use of corticosteroids.
15. For all tumor types:
Marrow function characterized by
-Absolute neutrophil count less than 500/mcL (must be present off growth factors)
Organ function characterized by
* Total bilirubin greater than 3 times upper limit of normal
* AST (SGOT)/ALT (SGPT) greater than 4 times upper limit of normal
* Creatinine clearance less than 50 cc/min based on a 24 hour urine collection
* Left ventricular ejection fraction less than 40% by echocardiogram (ECHO)
* Hypercalcemia greater than 2.5 mmol/L
For all Hematologic malignancies:
Marrow function characterized by
* Neutrophil count less than or equal to 500/mcl
* Platelets less than or equal to 20,000/mcl
16. HIV-positive patients
17. Hepatitis C positive patients (Hep C PCR positive)
18. Active Hepatitis B infection (Hep B surface antigen positive)
19. Pregnant or nursing
20. Psychiatric illness/social situations that would limit compliance with study requirements and ability to comprehend the investigational nature of the study and provide informed consent.
18 Years
70 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
National Heart, Lung, and Blood Institute (NHLBI)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Richard W Childs, M.D.
Role: PRINCIPAL_INVESTIGATOR
National Heart, Lung, and Blood Institute (NHLBI)
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Gautier JF, Ravussin Y. A New Symptom of COVID-19: Loss of Taste and Smell. Obesity (Silver Spring). 2020 May;28(5):848. doi: 10.1002/oby.22809. Epub 2020 Apr 1. No abstract available.
Last J. Informed consent/consentement eclaire. Ann R Coll Physicians Surg Can. 1992 Aug;25(5):263-4. No abstract available.
Farag SS, Caligiuri MA. Human natural killer cell development and biology. Blood Rev. 2006 May;20(3):123-37. doi: 10.1016/j.blre.2005.10.001. Epub 2005 Dec 20.
Goy A, Younes A, McLaughlin P, Pro B, Romaguera JE, Hagemeister F, Fayad L, Dang NH, Samaniego F, Wang M, Broglio K, Samuels B, Gilles F, Sarris AH, Hart S, Trehu E, Schenkein D, Cabanillas F, Rodriguez AM. Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2005 Feb 1;23(4):667-75. doi: 10.1200/JCO.2005.03.108. Epub 2004 Dec 21.
Related Links
Access external resources that provide additional context or updates about the study.
NIH Clinical Center Detailed Web Page
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
08-H-0186
Identifier Type: -
Identifier Source: secondary_id
080186
Identifier Type: -
Identifier Source: org_study_id