Haploidentical Natural Killer (NK) Cells in Patients With Relapsed or Refractory Neuroblastoma

This study has been terminated.
(Slow accrual.)
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00698009
First received: June 12, 2008
Last updated: October 23, 2012
Last verified: October 2012
  Purpose

Primary:

Evaluate safety, feasibility, persistence, and anti-tumor effect of infused haploidentical donor-derived natural killer (NK) cells and low-dose interleukin-2 (IL-2).

Secondary:

  • Quantification of cytokine levels;
  • Assessment of NK cell immunophenotype and function.

Condition Intervention Phase
Neuroblastoma
Drug: Fludarabine
Drug: Cyclophosphamide
Biological: Natural Killer Cell Infusion
Drug: Mesna
Drug: Interleukin-2
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Study to Infuse Haploidentical Natural Killer Cells in Patients With Relapsed or Refractory Neuroblastoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Participant Disease Response [ Time Frame: 1 Year for overall patient response, or until disease progression ] [ Designated as safety issue: No ]
    Neuroblastoma International Response Criteria: Complete Response (CR): No evidence of disease (primary and metastasis) clinically & radiographic studies, (homovanillic acid (HVA)/vanillylmandelic acid (VMA) normal). Very Good Partial Response (VGPR): >90% reduction in primary tumor, resolution all metastatic tumor except bone. No new bone lesions and improvement on scan of all pre-existing lesions; HVA/VMA decreased >90%. Partial Response (PR): 50-90% reduction primary and all measurable metastatic lesions, 0-1 bone marrow samples with tumor; scans of bone lesions same as VGPR. HVA/VMA decreased 50-90%. Mixed Response (MR): > 50% reduction any measurable disease (primary or metastases); no new lesions; <25% increase in any existing lesion (exclude bone marrow evaluation). No Response (NR): No new lesions; < 25% increase in existing lesion. Progressive Disease (PD): Any new lesions. Increase <25% in measurable lesion, previous negative bone marrow positive for tumor.

  • Number of Participants Infused Haploidentical Donor-derived Natural Killer (NK) Cells and Low-dose Interleukin-2 (IL-2) [ Time Frame: 21 days, up to 1 year ] [ Designated as safety issue: No ]
    Feasibility of an infused allogeneic donor NK cell product and IL-2 following a cyclophosphamide and fludarabine preparative regimen to treat relapsed neuroblastoma after autologous peripheral blood stem cell (PBSC) transplant where feasibility is defined as being able to infuse NK cells on day 0.


Enrollment: 1
Study Start Date: June 2008
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fludarabine + Cyclophosphamide + NK Cell Infusion
Fludarabine 25 mg/m^2 intravenous (IV) Daily Over 30 minutes Starting 6 days before the NK cell infusion (considered Day -6) and once a day through Day -2. Cyclophosphamide 60 mg/kg IV Daily Over 2 Hours On Days -5 and -4. Natural Killer Cell Infusion on Day 0. Mesna 12 mg/kg By Vein, Over about 15 minutes, 5 Times Per Day on Days -5 and -4. Interleukin-2 subcutaneously three times weekly for 9 total doses following NK Cell Infusion.
Drug: Fludarabine
25 mg/m^2 By Vein Daily Over 30 minutes Starting 6 days before the NK cell infusion (considered Day -6) and once a day through Day -2.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Cyclophosphamide
60 mg/kg By Vein Daily Over 2 Hours On Days -5 and -4
Other Names:
  • Cytoxan
  • Neosar
Biological: Natural Killer Cell Infusion
Natural Killer Cell Infusion on Day 0.
Other Names:
  • Infusion of NK cells
  • NK Cell Infusion
Drug: Mesna
12 mg/kg By Vein, Over about 15 minutes, Five Times Per Day on Days -5 and -4.
Other Name: Mesnex
Drug: Interleukin-2

Received under skin three times weekly for 9 total doses following NK Cell Infusion:

For patients weighing 45 kg or more, dose administered is 10 Million units three times weekly for 9 total doses. For patients less than 45 kg, dose administered is 5 Million units/m2 (max dose 10 Million units) three times weekly for 9 total doses.

Other Names:
  • IL-2
  • Proleukin

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Inclusion Criteria: (Must be met within 28 days prior to initiating lymphodepleting conditioning regimen) The first two patients enrolled in this protocol, if they have undergone a previous autologous transplant, will need to be at least 6 months post-transplant and/or have available prior cryopreserved autologous peripheral blood stem cells. This criterion safeguards against the possibility that the lymphodepletion regimen may lead to prolonged myelosuppression in this patient population.
  2. Evidence of relapse or progression of neuroblastoma after autologous peripheral blood stem-cell transplantation or similar aggressive therapy; high risk neuroblastoma that is refractory to standard induction therapy.
  3. Measurable disease, with at least one of the following: One or more measurable radiographic abnormalities (X-ray, CT, MRI, PET); MIBG (metaiodobenzylguanidine) scan with uptake at a minimum of 1 site; Bone marrow with tumor cells seen on routine morphology (not by neuron specific enolase (NSE) staining or by immunocytology only). If the only bony or soft tissue lesion available for evaluation has been previously irradiated, the lesion must either a) have viable neuroblastoma on biopsy at least 4 weeks after radiation therapy or b) have measurable growth in the lesion after radiation.
  4. Donor must be related to the recipient.
  5. Off all systemic chemotherapeutic agents or retinoids for at least 21 days prior to NK infusion.
  6. Platelets >/= 50,000 * 10^ 9/L and hemoglobin (Hgb) >/= 9 g/dL, unsupported by transfusions in last seven days.
  7. absolute neutrophil count (ANC) >/= 1,000 * 10^ 9/L, unsupported by cytokines in last seven days.
  8. Off prednisone or other immunosuppressive medications for at least 3 days prior to both the lymphodepleting regimen and the NK infusion (This excludes chronic low dose steroids for adrenal replacement which may be continued).
  9. Karnofsky score or Lansky score >/= 60.
  10. Adequate renal function defined as: Serum creatinine (Cr), for adults less than or equal to 2 mg/dL, for children less than or equal to 2 mg/dL or less than or equal to 2 times upper limit of normal (ULN) for age (whichever is less). If these criteria are not met, then recipient must have a Cr clearance greater than 60 mL/min/1.73m^2.
  11. Adequate liver function defined as: Total bilirubin </=2 mg/dL and serum glutamate pyruvate transaminase (SGPT/Alanine aminotransferase, ALT) </= 2.5 * ULN for age (unless Gilbert's disease or abnormal liver function due to primary disease).
  12. Pulmonary symptoms controlled by medication and pulse oximetry greater than or equal to 92% room air.
  13. Females of childbearing potential (non childbearing is defined as premenarchal, greater than one year post-menopausal or surgically sterilized) must have a negative serum pregnancy test obtained within 2 weeks prior to registration and may not be breast feeding during the study. All males and females of childbearing potential are required to use a form of contraception considered effective and medically acceptable by the Investigator during the time of the study.
  14. Donor must meet standard medical eligibility criteria for allogeneic stem cell donation and be able and willing to undergo apheresis.
  15. Donor must have infectious disease marker testing [Hepatitis B, Hepatitis C, HIV, cytomegalovirus (CMV), Syphilis (RPR), Chagas, human T-cell lymphoma virus (HTLV), and West Nile Virus] and complete blood count (CBC), differential and platelet studies that meet standard medical eligibility criteria for allogeneic blood stem cell donation within 7 days of apheresis.
  16. Donor, if a female of childbearing potential (non-childbearing is defined as premenarchal, greater than one year post-menopause or surgically sterilized), must have a negative serum pregnancy test obtained within 14 days of apheresis and may not be breast feeding.

Exclusion Criteria:

  1. Exclusion Criteria: These criteria apply to both the start of the lymphodepleting regimen and to the NK infusion
  2. Evidence of HIV (human immunodeficiency virus) disease or positive serology for HIV.
  3. Currently requiring supplemental oxygen or on a ventilator.
  4. Currently undergoing dialysis.
  5. New detected cardiac arrhythmia not controlled with medical management within prior 72 hour period.
  6. Hypotension requiring pressor support within prior 72 hour period.
  7. Uncontrolled infection, daily fever greater than or equal to 39 degrees Celsius or new positive culture for bacteria, fungus, or virus within the 72 hours prior to NK-cell infusion.
  8. Ascites requiring paracentesis within prior 72 hour period.
  9. Seizure activity, clinically detectable encephalopathy or new focal neurologic deficits within prior 72 hour period.
  10. Donor may not have an uncontrolled infection within 7 days of apheresis.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00698009

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Susan S. Kelly, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00698009     History of Changes
Other Study ID Numbers: 2006-0752
Study First Received: June 12, 2008
Results First Received: October 23, 2012
Last Updated: October 23, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Neuroblastoma
Natural Killer Cell
NK Cell Infusion
Haploidentical Natural Killer (NK) Cells
Fludarabine
Fludarabine Phosphate
Fludara
Cyclophosphamide
Cytoxan
Neosar
Interleukin-2
IL-2
Proleukin
Mesna
Mesnex
Infusion of NK cells
Pediatric NK Cell Infusion
Pediatric Neuroblastoma
Pediatric NK
Pediatric

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Mesna
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Aldesleukin
Interleukin-2
Vidarabine
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic

ClinicalTrials.gov processed this record on July 24, 2014