Neoplasms

All Conditions

Rare Diseases

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Gaucher Disease Type 2

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Antibodies

Cyclophosphamide

Immunoglobulins

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

This is a phase I study to assess the safety and feasibility of combining HLA-mismatched (KIR ligand incompatible) NK cells with hu3F8 in high-risk NB patients. Following chemotherapy, patients will be treated in sequential groups with a minimum of 3 patients/ dose of NK cells. Three dose levels of NK cells, starting at dose level 1, will be evaluated in this treatment protocol. The goal dose for each dose level is the high boundary (e.g. 9.9x10\^6/kg in level 1; 14.9x10\^6/kg in level 2, etc), but a range is provided to allow for cases where the goal dose cannot be achieved.

chemotherapy with intravenous (IV) cyclophosphamide 50mg/kg/day (for patients with body weight\<70kg) or 1500mg/m\^2/day (for patients with body weight ≥70kg) for two days (days -6 and -5).

cyclophosphamide

Day 0: NK cell infusion. NK cells are resuspended in Normasol at a concentration no less than 5 x 10\^6cells/mL. The patient is pre-medicated as per standard cell product infusion. The cell product is infused through a central venous catheter. Patients will be evaluated clinically by vital signs pre- and approximately 30 minutes post infusion of NK cells and thereafter at approximately 1 hour intervals for 4 hours.

NK cells

On Days -1, +1, +5, +7 and +9 hu3F8 is administered at 1.68 mg/kg/day and infused over \~30-90 minutes

hu3F8

On day 0, daily from +2 through +4, day +6, and day +8, rIL-2 is administered subcutaneously at 6 x 10\^5 U/m\^2/day.

rIL-2

Shakeel Modak, MD

This is a phase I study. The purpose of this study is to see if it is safe and feasible to give the participant cyclophosphamide (a type of chemotherapy), natural killer (NK) cells, and an antibody called Hu3F8 as a treatment for neuroblastoma. NK cells are a type of white blood cell.

Funding Source- FDA OOPD

Humanized Anti-GD2 Antibody Hu3F8 and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma

Phase I Study of the Humanized Anti-GD2 Antibody Hu3F8 and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma

as defined by International NB Response Criteria. Disease status is defined by the International NB Response Criteria. Complete response/remission (CR): no evidence of disease. Very good partial response/remission (VGPR): \>90% decrease in all disease parameters, except bone scan unchanged or improved; bone marrow must be free of disease. Partial response/remission: \>50% decrease in all disease parameters, except bone scan unchanged or improved; no more than 1 positive bone marrow site. Mixed response: \>50% decrease in \>1 but not all disease markers. Stable disease: \<50% decrease in all tumor markers. Progressive disease: new lesion, or \>25 % increase in any disease marker.

Y-mAbs Therapeutics

Memorial Sloan Kettering Cancer Center

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma

Fallopian Tube Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Germ Cells Tumors

Fallopian Tube Cancer

Ovarian Germ Cell Tumor

Anti-Infective Agents

Analgesics

Fludarabine

Fludarabine phosphate

Aldesleukin

Interleukin-2

Allopurinol

Antimetabolites

Antiviral Agents

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Enzyme Inhibitors

Antioxidants

Protective Agents

This group includes patients that received all chemotherapy, infusion of natural killer (NK) cells and total body irradiation per protocol.

1. Allopurinol 300 mg by mouth daily (unless known allergy) before beginning chemotherapy and continuing through day 14 post NK cell infusion. 2. Cyclophosphamide 60 mg/m\^2 on Days 4 and 5 preceding NK cell infusion. 3. Fludarabine phosphate 25 mg/m\^2 on Days 6 through 2 preceding NK cell infusion. 4. Radiation: total-body irradiation 200 cGy Day 1 preceding NK cell infusion. 5. Allogeneic natural killer cells- Given day 0 - dose of 1.5-8.0 \* 10\^7/kg. 6. Aldesleukin 10 million units 3 times/week for a total of 6 doses beginning Day 0.

This group includes patients that received chemotherapy and infusion of natural killer cells, but did not receive total body irradiation.

1. Allopurinol 300 mg by mouth daily (unless known allergy) before beginning chemotherapy and continuing through day 14 post NK cell infusion. 2. Cyclophosphamide 60 mg/m\^2 on Days 4 and 5 preceding NK cell infusion. 3. Fludarabine phosphate 25 mg/m\^2 on Days 6 through 2 preceding NK cell infusion. 4. Allogeneic natural killer cells- Given day 0 - dose of 1.5-8.0 \* 10\^7/kg. 5. Aldesleukin 10 million units 3 times/week for a total of 6 doses beginning Day 0.

All patients are to receive allopurinol 300 mg PO daily (unless known allergy) before beginning chemotherapy and continuing through day 14 post natural killer cell infusion.

60 mg/m\^2 on Days 4 and 5 preceding natural killer cell infusion.

25 mg/m\^2 on Days 6 through 2 preceding natural killer cell infusion.

200 cGy Day 1 preceding natural killer cell infusion.

total-body irradiation

Given day 0 - dose of 1.5-8.0 \* 10\^7/kg

Allogeneic natural killer cells

10 MU 3 times/week for a total of 6 doses beginning Day 0

Melissa A. Geller, MD

RATIONALE: Giving chemotherapy, such as cyclophosphamide and fludarabine, and total-body irradiation before a donor natural killer cell infusion helps stop the growth of tumor cells. It also helps stop the patient's immune system from rejecting the donor's natural killer cells. Aldesleukin may stimulate the natural killer cells to kill ovarian, fallopian tube, or primary peritoneal cancer cells. Treating the donor natural killer cells with aldesleukin may help the natural killer cells kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving laboratory-treated donor natural killer cells together with aldesleukin works when given after cyclophosphamide, fludarabine, and total-body irradiation in treating patients with recurrent and/or metastatic ovarian, fallopian tube, or primary peritoneal cancer.

OBJECTIVES:

Primary

* To evaluate the in vivo expansion of an infused allogeneic natural killer (NK) cell product following a preparative regimen comprising cyclophosphamide, fludarabine phosphate, and total-body irradiation in treating patients with recurrent and/or metastatic ovarian, fallopian tube, or primary peritoneal cancer.

Secondary

* To characterize the quantitative and qualitative toxicities of this treatment regimen.
* To estimate disease response (complete or partial response) or clinical benefit (stable disease for \> 6 months) as measured by Response Evaluation Criteria in Solid Tumours (RECIST) criteria.
* To estimate time to progression and overall survival.
* To estimate the association between clinical response and donor/recipient KIR ligand matching status.

Tertiary

* To evaluate immune activation of the in vivo expanded haploidentical allogeneic NK cells and its effect on the immune system.

OUTLINE:

* Preparative regimen: Patients receive fludarabine phosphate IV on days 6 to 2 preceding natural killer (NK) cell infusion and cyclophosphamide IV on days 5 and 4 preceding NK cell infusion. Patients also undergo total-body irradiation on day 1 preceding NK cell infusion.
* Allogeneic natural killer (NK) cell administration and aldesleukin: Patients receive aldesleukin-activated haploidentical allogeneic NK cells intravenously (IV) on day 0. Beginning 4-6 hours after allogeneic NK cell infusion, patients receive aldesleukin subcutaneously (SC) 3 times a week for 6 doses.

Patients achieving any initial response (complete or partial response) or a clinical benefit (stable disease for \> 6 months) who progress after 6 months may receive 1 re-treatment course as above.

Blood samples are collected at baseline, on days 0, 7, 14, and 28, and then at 2 and 3 months post NK cell infusion for cytokine measurements, immunophenotyping, functional analyses, and testing for persistence of donor cells.

After completion of study treatment, patients are followed periodically for at least 1 year.

Allogeneic Natural Killer Cells in Patients With Recurrent Ovarian Cancer, Fallopian Tube, and Primary Peritoneal Cancer

MT2007-19R: WCC #53 Allogeneic Natural Killer Cells in Patients With Recurrent Ovarian Cancer, Fallopian Tube, and Primary Peritoneal Cancer

Detection of an absolute donor derived cell count of \> or = 100 cells/mL after NK cell infusion.

Response Evaluation Criteria in Solid Tumors (RECIST) criteria: Complete Response (CR)-Disappearance of all target lesions (TL); Partial Response (PR)-\< or = 30% decrease in the sum of the longest diameter (LD) of TL, reference baseline sum LD; Stable Disease (SD)-Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference the smallest sum LD since the treatment started; Progressive Disease (PD)- \< or = 20% increase in the sum of the LD of TL, reference the smallest sum LD recorded since treatment started or appearance of \< or = 1 new lesion.

Median number of days from first date of treatment to date of disease progression (appearance of new metastatic lesions or objective tumor progression). Defined by computated tomography (CT) imaging based on Response Evaluation Criteria In Solid Tumors (RECIST): Progressive Disease (PD) \> or = 20% increase in sum of all target or any new lesions.

Median number of days patients alive from date of treatment to date of death or date of last follow-up if censored.

Masonic Cancer Center, University of Minnesota

Adverse event collection for the purposes of this study focused on targeted adverse events and unexpected adverse events at specific time points in relation to the NK cell infusion and post infusion IL-2 injections.

This group includes all patients consented to participate in this study.

All Patients Enrolled

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Endpoint for association of clinical benefit response with donor/recipient KIR ligand matching status is not evaluable due to 0 complete responders.

Correlative laboratory objectives are irrelevant due to ineffectiveness of study regimen.

Melissa Geller, M.D.

This group includes patients with recurrent ovarian, fallopian tube or primary peritoneal cancer who received at least one dose of chemotherapy (cyclophosphamide 60 mg/m\^2 and fludarabine 25 mg/m\^2 for 2 doses, and aldesleukin 10 million units for 6 doses), infusion of natural killer cells (1.5-8.0 \* 10\^7 kg) and/or total body irradiation per protocol (200 Gy on Day 1 preceding natural killer cell infusion).

Ovarian/Fallopian Tube/Peritoneal Cancer Patients

Number of Patients With In Vivo Expansion of Infused Allogeneic Natural Killer (NK) Cell Product

Complete Response

Partial Response

Stable Disease

Progressive Disease

This group includes patients with recurrent ovarian, fallopian tube or primary peritoneal cancer who received at least one dose of chemotherapy (cyclophosphamide 60 mg/m\^2 and fludarabine 25 mg/m\^2 for 2 doses, and aldesleukin 10 million units for 6 doses), infusion of natural killer cells (1.5-8.0 \* 10\^7 kg) and no total body irradiation.

No Total Body Irradiation

This group includes patients with recurrent ovarian, fallopian tube or primary peritoneal cancer who received at least one dose of chemotherapy (cyclophosphamide 60 mg/m\^2 and fludarabine 25 mg/m\^2 for 2 doses, and aldesleukin 10 million units for 6 doses), infusion of natural killer cells (1.5-8.0 \* 10\^7 kg) and total body irradiation (200 Gy on Day 1 preceding natural killer cell infusion).

Total Body Irradiation

Includes 12 patients that completed treatment per protocol criteria.

Number of Patients Per Disease Response

Median Number of Days to Progression

This group includes patients that received chemotherapy, infusion of natural killer cells and total body irradiation per protocol.

This group includes patients that received chemotherapy, infusion of natural killer cells and no total body irradiation per protocol.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Humanized Anti-GD2 Antibody Hu3F8 and Allogeneic Natural Killer Cells for High-Risk Neuroblastoma	NCT02650648	Neuroblastoma High-Risk	cyclophosphamid... NK cells hu3F8 rIL-2	-	Memorial Sloan Kettering Cancer Center
Allogeneic Natural Killer Cells in Patients With Recurrent Ovarian Cancer, Fallopian Tube, and Primary Peritoneal Cancer	NCT00652899	Fallopian Tube ... Ovarian Cancer Peritoneal Cavi...	Allopurinol Cyclophosphamid... Fludarabine pho... total-body irra... Allogeneic natu... Aldesleukin	18 Years -	Masonic Cancer Center, University of Minnesota

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