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

NCT00698009 | Terminated Phase 2 Results

• 1 other identifier: 2006-0752
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neuroblastoma

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Participant Disease Response

  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.

  1 Year for overall patient response, or until disease progression

• Number of Participants Infused Haploidentical Donor-derived Natural Killer (NK) Cells and Low-dose Interleukin-2 (IL-2)

  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.

  21 days, up to 1 year

Study Arms (1)

Fludarabine + Cyclophosphamide + NK Cell Infusion

EXPERIMENTAL

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; Drug: Cyclophosphamide; Biological: Natural Killer Cell Infusion; Drug: Mesna; Drug: Interleukin-2

Interventions

Fludarabine DRUG

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.

Also known as: Fludarabine Phosphate, Fludara

Fludarabine + Cyclophosphamide + NK Cell Infusion

Cyclophosphamide DRUG

60 mg/kg By Vein Daily Over 2 Hours On Days -5 and -4

Also known as: Cytoxan, Neosar

Fludarabine + Cyclophosphamide + NK Cell Infusion

Natural Killer Cell Infusion BIOLOGICAL

Natural Killer Cell Infusion on Day 0.

Also known as: Infusion of NK cells, NK Cell Infusion

Fludarabine + Cyclophosphamide + NK Cell Infusion

Mesna DRUG

12 mg/kg By Vein, Over about 15 minutes, Five Times Per Day on Days -5 and -4.

Also known as: Mesnex

Fludarabine + Cyclophosphamide + NK Cell Infusion

Interleukin-2 DRUG

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.

Also known as: IL-2, Proleukin

Fludarabine + Cyclophosphamide + NK Cell Infusion

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• Donor must be related to the recipient.
• Off all systemic chemotherapeutic agents or retinoids for at least 21 days prior to NK infusion.
• Platelets \>/= 50,000 \* 10\^ 9/L and hemoglobin (Hgb) \>/= 9 g/dL, unsupported by transfusions in last seven days.
• absolute neutrophil count (ANC) \>/= 1,000 \* 10\^ 9/L, unsupported by cytokines in last seven days.
• 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).
• Karnofsky score or Lansky score \>/= 60.
• 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.
• 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).
• Pulmonary symptoms controlled by medication and pulse oximetry greater than or equal to 92% room air.
• 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.
• Donor must meet standard medical eligibility criteria for allogeneic stem cell donation and be able and willing to undergo apheresis.
• 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.
• 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.

You may not qualify if:

• Evidence of HIV (human immunodeficiency virus) disease or positive serology for HIV.
• Currently requiring supplemental oxygen or on a ventilator.
• Currently undergoing dialysis.
• New detected cardiac arrhythmia not controlled with medical management within prior 72 hour period.
• Hypotension requiring pressor support within prior 72 hour period.
• 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.
• Ascites requiring paracentesis within prior 72 hour period.
• Seizure activity, clinically detectable encephalopathy or new focal neurologic deficits within prior 72 hour period.
• Donor may not have an uncontrolled infection within 7 days of apheresis.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center

MeSH Terms

Conditions

Neuroblastoma

Interventions

fludarabine; fludarabine phosphate; Cyclophosphamide; Mesna; Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Results Point of Contact

• Title: Eugenie S Kleinerman,MD/Professor, Pediatrics - Research
• Organization: UT MD Anderson Cancer Center

ekleiner@mdanderson.org

(713) 497-6226

Study Officials

• Susan S. Kelly, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2008
• First Posted: June 16, 2008
• Study Start: June 1, 2008
• Primary Completion: June 1, 2012
• Study Completion: June 1, 2012
• Last Updated: September 24, 2020
• Results First Posted: November 22, 2012

Record last verified: 2020-09

Locations

US (1)