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

Purpose

Funding Source - FDA OOPD FDR004128

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	Drug: cyclophosphamide, vincristine, topotecan ,allogeneic NK cells & 3F8	Phase 1


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: Neuroblastoma

Drug Information available for: Cyclophosphamide Vincristine sulfate Topotecan hydrochloride Topotecan

Genetic and Rare Diseases Information Center resources: Neuroblastoma Neuroepithelioma

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 2017
Estimated Primary Completion Date:	April 2017 (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, patients will be treated in sequential groups of 3 patients/dose of NK cells. Four 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. Patients can receive up to 3 cycles of treatment on protocol. For subsequent cycles, patients will be treated at either less than or at the same dose level of NK cells as their first cycle.	Drug: 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 during their first cycle. If receiving a second and/or third cycle, the only chemotherapy patients will receive is cyclophosphamide at 50 mg/kg/day for 2 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, patients will be treated in sequential groups of 3 patients/dose of NK cells. Four 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. Patients can receive up to 3 cycles of treatment on protocol. For subsequent cycles, patients will be treated at either less than or at the same dose level of NK cells as their first cycle.

Drug: 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 during their first cycle. If receiving a second and/or third cycle, the only chemotherapy patients will receive is cyclophosphamide at 50 mg/kg/day for 2 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


Ages Eligible for Study:	Child, Adult, Senior
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 approximately 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

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: 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


Responsible Party:	Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00877110 History of Changes
Other Study ID Numbers:	09-011 MSKCC09011 FDR004128
Study First Received:	April 6, 2009
Last Updated:	March 30, 2016
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 Antibodies Immunosuppressive Agents	Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Phytogenic Tubulin Modulators Antimitotic Agents Mitosis Modulators Topoisomerase I Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 26, 2016