Anti-GD2 3F8 Antibody and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma - Full Text View

Sponsor:	Memorial Sloan-Kettering Cancer Center
Information provided by (Responsible Party):	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00877110

Purpose

The goal of this study is to see if it is safe and feasible to give chemotherapy, natural killer (NK) cells, and an antibody called 3F8. The NK cells must come from a family member who shares half of the HLA proteins which are immune proteins important in transplant. NK cells are a type of white blood cell. They can recognize and kill abnormal cells in the body and can work together with antibodies to kill target cells. The antibody 3F8 specifically recognizes a protein present on the target cancer cell.

Condition	Intervention	Phase
Neuroblastoma Bone Marrow, Sympathetic Nervous System	Other: cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8	Phase I

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Study of Anti-GD2 3F8 Antibody and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma

Resource links provided by NLM:

Genetics Home Reference related topics: neuroblastoma

MedlinePlus related topics: Cancer Neuroblastoma

Drug Information available for: Cyclophosphamide Vincristine Topotecan hydrochloride Topotecan Vincristine sulfate

U.S. FDA Resources

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

Assess the feasibility and safety of administering allogeneic haploidentical NK infusions with 3F8 in patients with high-risk NB [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Estimate the anti-NB effect of allogeneic NK infusions plus 3F8 [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Assess the impact of KIR/HLA immunogenetics on disease response to NK/3F8 [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Assess the relationship between CD16 polymorphism and ADCC in vitro [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment:	72
Study Start Date:	April 2009
Estimated Study Completion Date:	April 2012
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: chemotherapy, allogeneic NK cells, 3F8 This is a phase I study to assess the safety and feasibility of combining HLA-mismatched (KIR ligand incompatible) NK cells with 3F8 in high-risk NB patients. Following chemotherapy with CTV, patients will be treated in sequential groups of 3-10 patients/dose of NK cells. Three dose levels of NK cells, starting at dose level I, will be evaluated in this treatment protocol. In the unlikely case toxicity is encountered at dose level I, patients will then be treated at the lower dose level 0.	Other: cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8 Patients will receive combination chemotherapy with intravenous (IV) cyclophosphamide 70mg/kg/day (for patients with body weight<70kg) or 2100mg/m2/day (for patients with body weight ≥70kg) for two days, IV vincristine 0.067mg/kg or 2mg/m2/day (lower of the two doses to be chosen; maximum 2mg) for one day, and IV topotecan 2.4 mg/m2/day for 3 days. On Day 0, patients will receive a single dose of allogeneic NK cells isolated from a HLA-haploidentical related donor. On day +3, the patient will start daily infusion of 3F8 for 5 days. The treatment schedule may require minor adjustment by ±1 day as clinically indicated (e.g. due to PDH closure for holidays or due to inclement weather).

Arms

Assigned Interventions

Experimental: chemotherapy, allogeneic NK cells, 3F8

This is a phase I study to assess the safety and feasibility of combining HLA-mismatched (KIR ligand incompatible) NK cells with 3F8 in high-risk NB patients. Following chemotherapy with CTV, patients will be treated in sequential groups of 3-10 patients/dose of NK cells. Three dose levels of NK cells, starting at dose level I, will be evaluated in this treatment protocol. In the unlikely case toxicity is encountered at dose level I, patients will then be treated at the lower dose level 0.

Other: cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8

Patients will receive combination chemotherapy with intravenous (IV) cyclophosphamide 70mg/kg/day (for patients with body weight<70kg) or 2100mg/m2/day (for patients with body weight ≥70kg) for two days, IV vincristine 0.067mg/kg or 2mg/m2/day (lower of the two doses to be chosen; maximum 2mg) for one day, and IV topotecan 2.4 mg/m2/day for 3 days. On Day 0, patients will receive a single dose of allogeneic NK cells isolated from a HLA-haploidentical related donor. On day +3, the patient will start daily infusion of 3F8 for 5 days. The treatment schedule may require minor adjustment by ±1 day as clinically indicated (e.g. due to PDH closure for holidays or due to inclement weather).

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Diagnosis of NB as defined by international criteria, i.e., histopathology (confirmed by the MSKCC Department of Pathology) or bone marrow metastases plus high urine catecholamine levels
High-risk NB as defined by risk-related treatment guidelines and the International NB Staging System,57 i.e., stage 4 with (any age) or without (>365 days of age) MYCN amplification, MYCN-amplified stage 3 (unresectable; any age), or MYCN-amplified stage 4S.
Patients must have a history of tumor progression or persistent disease or failure to achieve complete response following standard therapy.
Patients must have evaluable (microscopic marrow metastasis, elevated tumor markers, positive MIBG or PET scans) or measurable (CT, MRI) disease documented after completion of prior systemic therapy.
Disease staging within one month of treatment.
Human anti-mouse antibody (HAMA) titer <1000 Elisa units/ml if applicable
Available autologous stem cells: ≥2 x 106 CD34+ cells/kg
Adequate cardiac function as measured by echocardiogram
Eligible NK donor
Signed informed consent indicating awareness of the investigational nature of this program.

Donor Eligibility

Donor is blood-related and HLA-haploidentical to the recipient.
Donor has undergone serologic testing for transmissible diseases as per blood banking guidelines for organ and tissue donors. Tests include but are not limited to: HepBsAg, HepBsAb, HepBcAb, HepC antibody, HIV, HTLV I and II, VZV, CMV and VDRL, West Nile Virus and Chagas screen. Donor must have normal negative test results for HIV, HTLV I and II, and West Nile Virus. Donor exposure to other viral pathogens will be discussed on a case-by-case basis by the investigators.
Donor must be able to undergo leukopheresis for total volume of 10-15 liters.
There is no age restriction for the donor.

Exclusion Criteria:

Patients with CR/VGPR disease
Existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity > or = to grade 3 except for hearing loss, alopecia, anorexia, nausea, hyperbilirubinemia and hypomagnesemia from TPN, which may be grade 3
ANC should be >500/uL; platelet count >25K/uL.
History of allergy to mouse proteins
Active life-threatening infection
HAMA titer >1000 Elisa units/ml
Inability to comply with protocol requirements

Donor Exclusion Criteria

Cardiac risk factors precluding ability to undergo leukopheresis
Concurrent malignancy or autoimmune disease
Donor is pregnant.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00877110

Contacts

Contact: Shakeel Modak, MD	212-639-7623
Contact: Katharine Hsu, M.D., Ph.D.	646-888-2667

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center	Recruiting
New York, New York, United States, 10065
Contact: Shakeel Modak, MD 212-639-7623
Contact: Katharine Hsu, M.D., Ph.D. 646-888-2667
Principal Investigator: Shakeel Modak, MD

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Investigators

Principal Investigator:

Shakeel Modak, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00877110 History of Changes
Other Study ID Numbers:	09-011
Study First Received:	April 6, 2009
Last Updated:	November 21, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:

BETA-D-GLUCAN
CYCLOPHOSPHAMIDE (CYTOXAN)
MAB 131 I - 3F8
TOPOTECAN

VINCRISTINE
Neuroblastoma
09-011

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
Cyclophosphamide
Vincristine
Topotecan
Immunosuppressive Agents
Immunologic Factors

Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012