Fludarabine IV infusion over 30 minutes on D-7 to D-3. The dose will be 30 mg/m2/dose (adjusted for renal function). Melphalan: IV infusion over 30-60 minutes, depending on volume, on D-2. The dose will be 100mg/m2.Total body irradiation: 200 cGy AP/PA with 4MV or 6MV photons at 8 12 cGy/min at the point of prescription (average separation of measurements at mediastinum, abdomen, and hips) will be administered in a single fraction on day -1. Bone Marrow will be harvested and infused on day 0. Post-transplantation Cyclophosphamide 50mg/kg will be given on D+3 post-transplant (within 60-72 hr of marrow infusion) and on D+4 post-transplant. Tacrolimus begins on Day 5, at least 24 hours after completion of posttransplantation Cy at 0.015mg/kg IBW/dose IV over 3 hours every 12 hours. Mycophenolic acid mofetil (MMF) F will be given at a dose of 15 mg/kg PO TID (based upon actual body weight) with the maximum total daily dose not to exceed 3 grams (1 g PO TID).

Refractory and/or Relapsed Metastatic Solid Tumors

Cyclophosphamide

Fludarabine

low dose total body irradiation

Melphalan

Tacrolimus

Johns Hopkins All Children's Hospital

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Albert Einstein College of Medicine, Children's Hospital at Montefiore

New York Medical Center/ Maria Fareri Children's Hospital

Levine Cancer Institute/ Atrium Health

Reduced Intensity Haploidentical BMT for High Risk Solid Tumors

A Phase II Trial of Reduced Intensity Conditioning and Partially HLA-mismatched (HLA-haploidentical) Related Donor Bone Marrow Transplantation for High-risk Solid Tumors

Safety of shortened duration immunosuppression assessed by the number of participants with non-relapse mortality (NRM) and grade III-IV acute graft versus host disease (Przepiorka criteria stages the degree of organ involvement in the skin, liver and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least sever and Stage 4+ being most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, liver 4+))

Overall survival in patients receiving reduced intensity conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow.

Cumulative incidence by competing risks analysis of relapse in patients receiving reduced intensity conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow.

Time from start of intervention to death without relapse in patients receiving reduced intensity conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow.

Number of months from start of intervention until first adverse event as defined as relapse/disease progression or death by CTCAE v5.0 in participants receiving reduced intensity conditioning haploBMT

Number of months alive without progression in patients receiving reduced intensity conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow.

Number of months alive without progression (as defined by RECIST, Any new lesion or increase of a measurable lesion by >25%; previous negative marrow positive for tumor. ** MIBG scan must be negative for patient to be classified as having a complete response. New site of disease documented by MIBG scan qualifies patient as having progressive disease.) in patients receiving reduced intensity conditioning and transplantation of partially human leukocyte antigen (HLA)-mismatched bone marrow.

To determine the cumulative incidence by competing risks analysis of acute GVHD as defined by Przepiorka criteria stages the degree of organ involvement in the skin, liver and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least sever and Stage 4+ being most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, liver 4+)

To determine the cumulative incidence by competing risks analysis of chronic GVHD as defined by the NIH Consensus criteria

To document any unexpected toxicities after RIC haploidentical BMT.

To compare the tumor microenvironment, circulating tumor cells, and expression of MHC antigens as well as tumor specific antigens pre- and post BMT

To document the incidence of significant viral, bacterial and fungal infections as defined by the NCI's Common Terminology Criteria for Adverse Events (CTCAE) as well as the fungal criteria (proven and probable)

% of patients achieving donor bone marrow chimerism >/= 95% at Day 60

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Fludarabine 25 mg/m^2 intravenous (IV) Daily Over 30 minutes Starting 6 days before the NK cell infusion (considered Day -6) and once a day through Day -2. Cyclophosphamide 60 mg/kg IV Daily Over 2 Hours On Days -5 and -4. Natural Killer Cell Infusion on Day 0. Mesna 12 mg/kg By Vein, Over about 15 minutes, 5 Times Per Day on Days -5 and -4. Interleukin-2 subcutaneously three times weekly for 9 total doses following NK Cell Infusion.

Fludarabine + Cyclophosphamide + NK Cell Infusion

Sex: Female, Male

Region of Enrollment

Neuroblastoma International Response Criteria: Complete Response (CR): No evidence of disease (primary and metastasis) clinically & radiographic studies, (homovanillic acid (HVA)/vanillylmandelic acid (VMA) normal). Very Good Partial Response (VGPR): >90% reduction in primary tumor, resolution all metastatic tumor except bone. No new bone lesions and improvement on scan of all pre-existing lesions; HVA/VMA decreased >90%. Partial Response (PR): 50-90% reduction primary and all measurable metastatic lesions, 0-1 bone marrow samples with tumor; scans of bone lesions same as VGPR. HVA/VMA decreased 50-90%. Mixed Response (MR): > 50% reduction any measurable disease (primary or metastases); no new lesions; <25% increase in any existing lesion (exclude bone marrow evaluation). No Response (NR): No new lesions; < 25% increase in existing lesion. Progressive Disease (PD): Any new lesions. Increase <25% in measurable lesion, previous negative bone marrow positive for tumor.

Participant Disease Response

Feasibility of an infused allogeneic donor NK cell product and IL-2 following a cyclophosphamide and fludarabine preparative regimen to treat relapsed neuroblastoma after autologous peripheral blood stem cell (PBSC) transplant where feasibility is defined as being able to infuse NK cells on day 0.

Number of Participants Infused Haploidentical Donor-derived Natural Killer (NK) Cells and Low-dose Interleukin-2 (IL-2)

Overall Study

Eugenie S Kleinerman,MD/Professor, Pediatrics - Research

Neuroblastoma

25 mg/m^2 By Vein Daily Over 30 minutes Starting 6 days before the NK cell infusion (considered Day -6) and once a day through Day -2.

60 mg/kg By Vein Daily Over 2 Hours On Days -5 and -4

Natural Killer Cell Infusion

12 mg/kg By Vein, Over about 15 minutes, Five Times Per Day on Days -5 and -4.

Mesna

Received under skin three times weekly for 9 total doses following NK Cell Infusion:
For patients weighing 45 kg or more, dose administered is 10 Million units three times weekly for 9 total doses. For patients less than 45 kg, dose administered is 5 Million units/m2 (max dose 10 Million units) three times weekly for 9 total doses.

Interleukin-2

UT MD Anderson Cancer Center

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

Study to Infuse Haploidentical Natural Killer Cells in Patients With Relapsed or Refractory Neuroblastoma

M.D. Anderson Cancer Center

Brain Tumor

Retinoblastoma

Wilms Tumor

Mycoses

2.5 mg/kg twice daily for the first two days --> once daily

itraconazole

Samsung Medical Center

Efficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation

Clinical Study to Evaluate the Efficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation for Pediatric Solid Tumors

neuroblastoma/koorts

Reduced Intensity Haploidentical BMT for High Risk Solid Tumors

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

Efficacy of Prophylactic Itraconazole in High-Dose Chemotherapy and Autologous Hematopoietic Stem Cell Transplantation

Therapy for Children With Neuroblastoma

De meest complete database met geneeskrachtige kruiden, ondersteund door de wetenschap