Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Cohort 1: 1x10\^6 cells/kg Cohort 2: 1x10\^7 cells/kg

Cohort 3: 1x10\^6 cells/kg Cohort 4: 3x10\^6 cells/kg Cohort 5: 1x10\^7 cells/kg Cohort 6: 3x10\^7 cells/kg

Allogeneic NK cells

Allogeneic natural killer (NK) cells (MG4101) were manufactured from normal healthy donor who underwent leukapheresis. These cells were processed based on a novel method for ex vivo activation and expansion using an irradiated and activated autologous feeder cell system. MG4101 has anti-tumor activities against various tumors including malignant lymphomas in vitro as well as in vivo tumor model.

Allogeneic Natural Killer (NK) Cell Therapy in Patients With Lymphoma or Solid Tumor

A Phase I Study of Allogeneic NK Cell Therapy in Patients With Refractory/Relapsed Lymphoma or Solid Tumor

DLT is defined as follows:

* Any toxicity at grade 3 or over for 5 days or more
* All grade 4 toxicities
* GVHD at grade 2 or over

RECIST v1.1 for solid tumor or revised response criteria for malignant lymphoma

To quantify the persistence of donor NK cells in recipients

GC Biopharma Corp

Seoul National University Hospital

Tae Min Kim/Assistant Professor

Digestive System Diseases

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Colorectal Neoplasms

Neoplasms, Glandular and Epithelial

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Cetuximab

Antineoplastic Agents, Immunological

WU-NK-101 is a non-engineered Natural Killer (NK) cell derived from peripheral blood mononuclear cells (PBMC) that is cytokine-reprogrammed, expanded, and cryopreserved to create an allogeneic enhanced memory-like anti-tumor NK cell therapy product.

Each 8 week cycle in dose escalation is divided into two 28- days segments. Patients will receive WU-NK-101 (Days 1 and 15) in the first segment and a combination of cetuximab (500mg/m2 on Days 29 and 43) plus WU-NK-101 (Days 30 and 44) in the second segment.

Patients will receive cetuximab dosed at 500 mg/m2 on Days 1 and 15, and WU-NK-101 on Days 2 and 16, in each 4-week cycle. Depending on response patients may receive up to 6 cycles of treatment.

WU-NK-101 administered on Days 1, 15, 30 and 44

WU-NK-101 - Dose Escalation

Cetuximab 500mg/m2 administered on Days 29 and 43

Cetuximab - Dose Escalation

WU-NK-101 - Cohort Expansion

Cetuximab 500mg/m2 administered on Days 1 and 15

Cetuximab - Cohort Expansion

Eileen McNulty

Jan Davidson, MD, PhD

This study is a Phase 1b open-label study designed to characterize the safety, tolerability, and preliminary anti-tumor activity of WU-NK-101 in combination with cetuximab in patients with advanced and/or metastatic CRC (Cohort 1), and in patients with advanced and/or metastatic SCCHN (Cohort 2). The overall study will be comprised of two phases, a Dose Escalation Phase, and a Cohort Expansion Phase.

In the Dose Escalation Phase, up to 12 patients with either advanced and/or metastatic CRC or advanced and/or metastatic SCCHN will be treated with WU-NK-101, alone and in combination with cetuximab, in successive cohorts of 3 to 6 patients using a standard 3 + 3 design. Intra-patient dose escalation is not permitted. Patients may receive up to one 8-week cycle of treatment. Each 8-week cycle is divided into two 28-day segments, (Segments A and B).

During Segment A, only WU-NK-101 (monotherapy) will be administered. Segment A will consist of two doses of WU-NK-101 infused on Day 1 and Day 15. Patients that do not experience a dose limiting toxicity (DLT) will proceed to Segment B.

During Segment B, WU-NK-101 will be administered in combination with cetuximab (combination therapy). WU-NK-101 cells will be administered on Days 30 and 44. Cetuximab will be administered on Days 29 and 43 at 500 mg/m2 (FDA-approved dose).

Once the MTD/MAD is defined in the Dose Escalation Phase, up to 9 additional patients will be enrolled in 2 parallel, disease specific, expansion cohorts (Cohort 1 \[patients with CRC\] and Cohort 2 \[patients with SCCHN\]) to further characterize the safety, tolerability, and preliminary anti-tumor activity of WU-NK-101 cells in combination with cetuximab. Patients will receive cetuximab dosed at 500 mg/m2 on Days 1 and 15, and WU-NK-101 on Days 2 and 16, in each 4-week cycle.

At the end of Cycle 2, patients who achieve a partial response (PR) or stable disease (SD) may receive up to 4 additional cycles of treatment of WU-NK-101 cells in combination with cetuximab with disease assessments on Day 28 (+/- 3 days) of each even numbered cycle, for a maximum of 6 cycles.

In dose expansion patients will be enrolled in 2 parallel, disease specific cohorts to further characterize the safety, tolerability and preliminary anti- tumor activity of WU-NK-101 in combination with cetuximab

A Phase 1b Study of WU-NK-101 in Combination With Cetuximab

A Phase 1b Study of WU-NK-101 in Combination With Cetuximab for Advanced and/or Metastatic Colorectal Cancer (CRC) and Advanced and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of consent until the end of the study visit or at the end of treatment visit.

Maximum tolerated or administered dose of WU-NK-101 in combination with cetuximab

Time of response to the time of disease relapse, progression or death due to any cause

ORR is defined as the proportion of patients that achieve complete remission (CR) + partial response (PR) using modified Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)

Wugen, Inc.

Neuroblastoma

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Gaucher Disease Type 2

Neuroepithelioma

Antirheumatic Agents

Anti-Infective Agents

Anticonvulsants

Nootropic Agents

Dermatologic Agents

Analgesics

Amino Acids

Antibodies

Antibodies, Monoclonal

Etoposide

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Molgramostim

Sargramostim

Aldesleukin

Topotecan

Vincristine

Melphalan

Cisplatin

Lenograstim

Levetiracetam

Etoposide phosphate

Immunoglobulins

Busulfan

Isotretinoin

Tretinoin

Interleukin-2

Mechlorethamine

Dinutuximab

Mesna

Immunoglobulins, Intravenous

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

Topoisomerase I Inhibitors

Analgesics, Non-Narcotic

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

Adjuvants, Immunologic

Phenylalanine

Participants receive IV hu14.18K322A with each course of chemotherapy (cyclophosphamide, topotecan, cyclophosphamide, doxorubicin, vincristine, cisplatin, and etoposide). Mesna will be given prior to and after cyclophosphamide infusion. Peripheral blood stem cell harvest (PBSC) and surgical resection of primary tumor will be performed, if feasible. Intensification therapy includes busulfan, melphalan, and levetiracetam with peripheral blood stem cell transplantation. A course of hu14.18K322A with natural killer cell infusion will be given to consenting participants. Radiation therapy will follow PBSC transplant with the exception of any patient requiring emergent radiotherapy. MRD treatment includes hu14.18K322A, G-CSF, GM-CSF, interleukin-2 and isotretinoin.

Cells for infusion are prepared using the CliniMACS System.

cyclophosphamide

topotecan

hu14.18K322A

Following evaluation and approval by a member of the transplant staff and completion of the consent form by the participant, collection of peripheral blood stem cells (PBSC) may take place.

peripheral blood stem cell harvest

The primary tumor will be resected surgically following two initial courses of chemotherapy, if feasible. Patients who are unable to have their primary tumor resected after the initial two courses of induction chemotherapy will undergo surgery for resection of the primary tumor mass and careful lymph node staging.

surgical resection

cisplatin

etoposide

doxorubicin

vincristine

busulfan

melphalan

Transplantation of previously harvested peripheral blood stem cells.

peripheral blood stem cell transplantation

Natural killer (NK) cells obtained from a suitable donor will be given together with hu14.18K322A prior to early hematopoietic cell recovery. In the event there is not a suitable parental donor, consenting participants will receive an additional course of hu14.18K322A.

natural killer cell infusion

Radiation therapy to the primary and metastatic disease sites will follow peripheral blood stem cell transplant with the exception of any patient requiring emergent radiotherapy. External beam radiotherapy will be delivered to the primary site and select metastatic and bulky nodal sites.

radiation therapy

GM-CSF

G-CSF

mesna

levetiracetam

Given by continuous infusion during MRD maintenance, and SQ during induction.

interleukin-2

The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.

CliniMACS

Sara M. Federico, MD

Neuroblastoma is the most common extracranial solid tumor in childhood, with nearly 50% of patients presenting with widespread metastatic disease. The current treatment for this group of high-risk patients includes intensive multi-agent chemotherapy (induction) followed by myeloablative therapy with stem-cell rescue (consolidation) and then treatment of minimal residual disease (MRD) with isotretinoin. Recently a new standard of care was established by enhancing the treatment of MRD with the addition of a monoclonal antibody (ch14.18) which targets a tumor-associated antigen, the disialoganglioside GD2, which is uniformly expressed by neuroblasts. Despite improvement in 2-year event-free survival (EFS) of 20%, more than one-third of children with high-risk neuroblastoma (HR defined in) still cannot be cured by this approach. Therefore, novel therapeutic approaches are needed for this subset of patients. This study will be a pilot Phase II study of a unique anti-disialoganglioside (anti-GD2) monoclonal antibody (mAb) called hu14.18K322A, given with induction chemotherapy.

PRIMARY OBJECTIVE:

* To study the efficacy \[response: complete remission + partial remission (CR+PR)\] to two initial courses of cyclophosphamide and topotecan combined with hu14.18K322A (4 doses/course followed by GM-CSF) in previously untreated children with high-risk neuroblastoma.
* To estimate the event-free survival of patients with newly diagnosed high-risk neuroblastoma treated with the addition of hu14.18K322A to treatment.

SECONDARY OBJECTIVES:

* To study the feasibility of delivering hu14.18K322A to 6 cycles induction chemotherapy and describe the antitumor activity (CR+PR) of this 6 course induction therapy.
* To estimate local control and pattern of failure associated with focal intensity modulated or proton beam radiation therapy dose delivery in high-risk abdominal neuroblastoma.
* To describe the tolerability of four doses of hu14.18K322A with allogeneic natural killer (NK) cells from an acceptable parent, in the immediate post-transplant period \[day +2 - +5 after peripheral blood stem cell (PBSC) infusion\] in consenting participants.
* To describe the tolerability of hu14.18K322A with interleukin-2 and GM-CSF as treatment for minimal residual disease (MRD).

The phases of the study are:

1. Screening phase: Tests and evaluations will be done before treatment starts.
2. Induction phase: Includes chemotherapy plus hu14.18K322A mAb. Participants will also have surgery during this part of the study to remove as much tumor as possible.
3. Consolidation/Intensification phase: Includes high doses of chemotherapy and blood stem cell transplantation with additional, experimental "minimal residual disease" (MRD) treatment. Participants will also get radiation treatment to all sites of the tumor(s) after recovery from the stem cell transplant.
4. Maintenance/MRD treatment phase: With immune therapy in addition to the standard treatment with the drug isotretinoin.

Therapy for Children With Advanced Stage Neuroblastoma

Neuroblastoma Protocol 2012: Therapy for Children With Advanced Stage High-Risk Neuroblastoma

Per the 1993 INRC: measurable tumor defined as product of the longest x widest perpendicular diameter, elevated catecholamine levels and tumor cels in bone marrow. Complete Response (CR)-no evidence of primary tumor or metastases. Very Good Partial Response (VGPR)-\>90% reduction of primary tumor; no metastases; no new bone lesions, all pre-existing lesions improved. Partial Response (PR)-50-90% reduction of primary tumor; \>50% reduction in measurable sites of metastases; 0-1 bone marrow samples with tumor; number of positive bone sites decreased by \>50%. Mixed Response (MR)-\>50% reduction of any measurable lesion with \<50% reduction in other sites; no new lesions; \<25% increase in any existing lesion. No Response (NR)-no new lesions; \<50% reduction but \<25% increase in an any existing lesion. No Response (NR)-no new lesions; \<50% reduction but \<25% increase in any existing legions. Progressive Disease (PD)-any new/increased measurable lesion by \>25%; previous negative marrow positive.

EFS was estimated as time to relapse, progressive disease, secondary neoplasm, or death from any cause from enrollment. The EFS was estimated by Kaplan-Meier method

The study is designed to monitor the feasibility of delivering hu14.18K332A to 6 cycles of Induction chemotherapy. The feasibility of Induction therapy for this study will be to target no worse than 75%. A patient was considered as a "failure" for the 6 cycles of Induction therapy if the patient failed to complete Induction therapy within 155 days since treatment initiation due to toxicity or disease progression, unless the delay was a result of non-medical issues (e.g. not due to protocol toxicity). The proportion of patients who successfully received hu14.18K322A with 6 cycles of induction chemotherapy was estimated together with a 95% confidence interval. The response rate (CR + VGPR + PR) to 6 cycles of Induction chemoimmunotherapy was estimated together with the 95% confidence intervals

Local failure is defined as relapse or progression of disease at the primary site. The cumulative incidence of local failure will be estimated; competing events will include distant failure or death prior to local failure.

Number of patients who experience an unacceptable dose limiting toxicity (per CTCAE v 4.0) including the following toxicities: 1) toxicity requiring the use of pressors, including Grade 4 acute capillary leak syndrome or Grade3 and 4 hypotension; 2) Toxicity requiring ventilation support, including Grade 4 respiratory toxicity; 3) Grade 3 or 4 neurotoxicity with MRI evidence of new CNS thrombi, infarction or bleeding in any subject receiving the hu14.18K322A with NK cell combination; 4) Failure of recovery of ANC \> 500/mm3 by day 35 after PBSC infusion. Number of patients who experience Grade 3 or Grade 4 (per Common Toxicity Criteria v 4.0) veno occlusive disease (VOD).

Number of patients who experience an unacceptable dose limiting toxicity (per CTCAE v 4.0) including the following toxicities: 1) Toxicity requiring the use of pressors, including Grade 4 acute capillary leak syndrome or Grade 3 and 4 hypotension; 2) Toxicity requiring ventilation support, including Grade 4 respiratory toxicity; 3) Grade 3 or 4 neurotoxicity with MRI evidence of new CNS thrombi, infarction or bleeding.

Cookies for Kids' Cancer

CURE Childhood Cancer, Inc.

St. Jude Children's Research Hospital

All newly diagnosed, high-risk neuroblastoma participants \<19 years of age who had histologic proof of neuroblastoma or positive bone marrow for tumor cells with increased urine catecholamines, with adequate renal and hepatic function, no prior therapy and consent to the study.

NB2012 Therapy (Including Induction, Consolidation, and MRD) Plus Antibody (hu14.18K322A)

All newly diagnosed, high-risk neuroblastoma participants \<19 years of age who had histologic proof of neuroblastoma or positive bone marrow for tumor cells with increased urine catecholamines, with adequate renal and hepatic function, no prior therapy and consent to the study will receive Induction, Consolidation and MRD treatment with humanized anti-GD2 antibody (hu14.18K322A) included during Induction and Consolidation. A subset of patients also received hu14.18K322A during Consolidation.

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Cyclophosphamide and topotecan combined with humanized anti-GD2 antibody (hu14.18K322A)

NB2012 Therapy (Including Induction, Consolidation, and MRD) Antibody (hu14.18K322A)

Overall Response Rate [Complete Response + Very Good Partial Response + Partial Response (CR + VGPR + PR)]

All newly diagnosed, advanced stage, high-risk neuroblastoma participants \<19 years of age who had histologic proof of neuroblastoma or positive bone marrow for tumor cells with increased urine catecholamines, with adequate renal and hepatic function, no prior therapy and consent to the study.

Event-free Survival (EFS)

Feasibility of Delivering hu14.18K322A to 6 Cycles of Induction Therapy

NB2012 Therapy (Including Induction, Consolidation, and MRD) Antibody Antibody (hu14.18K322A)

Local Failure Rate and Pattern of Failure

All newly diagnosed, high-risk neuroblastoma participants \<19 years of age who had histologic proof of neuroblastoma or positive bone marrow for tumor cells with increased urine catecholamines, with adequate renal and hepatic function, no prior therapy and consent to the study. Patients had a parent to donate NK cells to be given during Consolidation.

Dose Limiting Toxicity (DLT) or Severe (Grade 3 or 4) VOD With hu14.18K322A With Allogeneic NK Cells in Consolidation

Dose Limiting Toxicity (DLT)

All newly diagnosed high-risk neuroblastoma participants \<19 years of age who had histologic proof of neuroblastoma or positive bone marrow for tumor cells with increased urine catecholamines, with adequate renal and hepatic function, no prior therapy and consent to the study will receive cyclophosphamide and topotecan combined with humanized anti-GD2 antibody (hu14.18K322A).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Allogeneic Natural Killer (NK) Cell Therapy in Patients With Lymphoma or Solid Tumor	NCT01212341	Malignant Lymph... Solid Tumors	Allogeneic NK c...	18 Years -	Seoul National University Hospital
A Phase 1b Study of WU-NK-101 in Combination With Cetuximab	NCT05674526	Colorectal Canc... Squamous Cell C...	WU-NK-101 - Dos... Cetuximab - Dos... WU-NK-101 - Coh... Cetuximab - Coh...	18 Years -	Wugen, Inc.
Allogeneic Natural Killer (NK) Cell Therapy in Patients With Lymphoma or Solid Tumor	NCT01212341	Malignant Lymph... Solid Tumors	Allogeneic NK c...	18 Years -	Seoul National University Hospital
Therapy for Children With Advanced Stage Neuroblastoma	NCT01857934	Neuroblastoma	cyclophosphamid... topotecan hu14.18K322A peripheral bloo... surgical resect... cisplatin etoposide doxorubicin vincristine busulfan melphalan peripheral bloo... natural killer ... radiation thera... GM-CSF G-CSF mesna levetiracetam interleukin-2 Isotretinoin CliniMACS	- 18 Years	St. Jude Children's Research Hospital
Therapy for Children With Advanced Stage Neuroblastoma	NCT01857934	Neuroblastoma	cyclophosphamid... topotecan hu14.18K322A peripheral bloo... surgical resect... cisplatin etoposide doxorubicin vincristine busulfan melphalan peripheral bloo... natural killer ... radiation thera... GM-CSF G-CSF mesna levetiracetam interleukin-2 Isotretinoin CliniMACS	- 18 Years	St. Jude Children's Research Hospital

Spots Global Cancer Trial Database for allogeneic nk cells