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

• Status: Terminated
• Trial end date: 2012-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Treatments: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2; Mesna; Vidarabine

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 bilirubinpyruvate transaminase (SGPT/Alanine aminotransferase, ALT)(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.