Natural Killer Cells and Bortezomib to Treat Cancer

NCT00720785 | Completed Phase 1 FDA Drug

• 2 other identifiers: 08018608-H-0186
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Natural killer (NK) cells are white blood cells that have a limited ability to kill cancer cells. This ability might be enhanced if they are given 24 hours after an injection of the drug bortezomib. This study will determine the following:

• 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. ...

Conditions

Pancreatic Ca; Colon/Rectal Ca; Chronic Myeloid Leukemia (CML); Multiple Myeloma; Carcinoma, Non-Small -Cell Lung

Keywords

Metastatic Solid Tumor; Chronic Myelogenous Leukemia (CML); Small Lymphocytic Lymphoma (SLL); Chronic Lymphocytic Leukemia (CLL); Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• safety 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 toxicity with bortezomib.

  Safety

  After each 3 week cycle

Study Arms (2)

1

EXPERIMENTAL

NK Cell Infusion (cell /kg pt wt)

Biological: NK cells

2

EXPERIMENTAL

1.3 mg/m2/dose administered as a 3 to 5 second bolusintravenous injection

Drug: Bortezomib

Interventions

Bortezomib DRUG

Parenteral formulation. It is supplied as a 3.5 mg single use vial containing a sterile lyophilized powder that requires reconstitution.

2

NK cells BIOLOGICAL

NK Cell Infusion

1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosed with histologically confirmed metastatic solid tumor - cancer of the lung (small cell or non small cell), prostate (adenocarcinoma), colorectum, kidney (renal cell carcinoma), pancreas (adenocarcinoma),or malignant melanoma, metastatic Ewing's sarcoma, or metastatic epithelial neoplasms and adenocarcinoma of unknown primary, and disease confirmed to be metastatic and unresectable for which standard curative or beneficial treatments are no longer effective
• 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.
• 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).
• At least 2 weeks since prior palliative radiotherapy.
• Ages greater than or equal to 18 years and less than or equal to 70 years.
• Evidence of progressive disease over a 3-month interval.
• RBC transfusion independent (solid tumor patients only).

You may not qualify if:

• Disease not evaluable radiographically (applies to solid tumor patients only).
• Disease involving greater than 25% of the liver radiographically (estimated based on review of liver lesions seen on CT scan).
• History of an allogeneic hematopoietic stem cell transplant.
• 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).
• Peripheral neuropathy of grade greater than 1, which would require reduction of bortezomib dose.
• Acute diffuse infiltrative pulmonary disease.
• Acute pericardial disease.
• Life expectancy less than 3 months.
• ECOG performance status 2, 3 or 4.
• 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.
• Ongoing or active infection
• Contraindication for administration of pentostatin, bortezomib, and/or interleukin-2.
• Allergy or hypersensitivity to bortezomib, boron or mannitol by history.
• Concurrent use of corticosteroids.
• For all tumor types:

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Last J. Informed consent/consentement eclaire. Ann R Coll Physicians Surg Can. 1992 Aug;25(5):263-4. No abstract available.

  PMID: 11651409 BACKGROUND

• 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.

  PMID: 16364519 BACKGROUND

• 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.

  PMID: 15613697 BACKGROUND

• 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.

  PMID: 32237199 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Multiple Myeloma; Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Bortezomib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Leukemia, B-Cell; Leukemia, Lymphoid; Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Richard W Childs, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 22, 2008
• First Posted: July 23, 2008
• Study Start: August 1, 2008
• Primary Completion: April 6, 2021
• Study Completion: April 6, 2021
• Last Updated: May 5, 2026

Record last verified: 2025-07-14

Locations

US (1)