Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

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

Ovarian Cancer

Ovarian Epithelial Cancer

Consolidation intensity-modulated whole-abdominal radiotherapy using helical tomotherapy to a total dose of 30 Gy in 1.5 Gy fractions

intensity-modulated whole-abdominal radiotherapy

Nathalie Rochet, MD

Juergen Debus, MD, PhD

Andreas Schneeweiss, MD

The primary objective of this phase-II study is to assess the toxicity of consolidation intensity-modulated whole-abdominal radiotherapy using tomotherapy in patients with advanced optimally debulked stage International Federation of Gynecology and Obstetrics (FIGO) III ovarian cancer with a complete remission after adjuvant chemotherapy.

36 patients will be treated to a total dose of 30 Gy in 1.5 Gy fractions. The planning target-volume includes the entire peritoneal cavity and the pelvic and para-aortal node regions. Intensity-modulated whole-abdominal radiotherapy allows an effective sparing of liver, kidneys and bone-marrow (vertebral bodies and pelvic bones).

Consolidation Whole Abdominal Intensity-Modulated Radiation Therapy (IMRT) in Advanced Ovarian Cancer

Consolidation Intensity-Modulated Whole Abdominal Radiotherapy for High-Risk Patients With Ovarian Cancer Stage FIGO III

Therapy compatibility defined as non-occurrence of life-threatening grade 4 (CTCAE v3.0) acute toxicity

Rate of incomplete radiotherapy due to treatment toxicity

Rate of delayed radiotherapy due to treatment toxicity

assessed using EORTC QLQ-C30 Questionnaire

Deutsche Krebshilfe e.V., Bonn (Germany)

University Hospital Heidelberg

Juergen Debus / Prof., M.D., PhD

Blood and Lymph Conditions

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Starting on day -6, 60mg/Kg cyclophosphamide by vein will be administrated. Day -5 to -1 fludarabine administrated by vein at 25 mg/m2. 24-48 hours after chemotherapy completion, NK cell infusion will be injected (day 0). On day 7 a second NK cell infusion will be administrated. First infusion consist of 5x10\^7/kg NK CD3-CD56+ NK cells. The second NK cell infusion will include up to 5x10\^8 CD3-CD56+ cells if no treatment related toxicity occurred. Subcutaneous IL-2 (1x10\^6 UI/m2) three times a week for two weeks will be administrated after first NK infusion.

cyclophosphamide

* First allogeneic haploidentical NK cell iv. infusion: 5x10e7/kg, NK CD3-CD56+ immunophenotype, 24-48h after chemotherapy
* Second allogeneic haploidentical NK cell iv. infusion: up to 5x10e8/kg, NK CD3-CD56+immunophenotype, 7 days after the first infusion.

NK cell infusion

1x10\^6 UI/m2 three times a week for two weeks from first NK infusion (day 0)

IL-2

Antonio Pérez Martínez, MD, PhD.

The main goal of this study is to evaluate the anti-relapse prophylactic activity of inoculating Natural Killer (NK) cells as consolidation therapy of acute myeloid leukemia in paediatric patients with cytologic remission. The patients included have intermediate risk of relapse and no indication for allogeneic hematopoietic stem cell transplantation.

After the standard induction and consolidation chemotherapy treatment, patients will receive five days of fludarabine to try to kill any minimal residual disease and prevent NK cell rejection. Two different NK cells infusions will be performed within one week (day 0 and 7). Interleukin 2 (IL-2) will be administrated to increase the cytotoxic activity of NK cells.

Hypothesis:

NK cells are the natural defence against cancer cells. Thus, supplementing compatible NK cells from a related donor might increase the probability to eliminate any residual chemotherapy resistant cell in Acute myelogenous leukemia patients.

Description:

NK cells will be donated from a compatible family member who has a certain genetic code in their blood, called HLA, which partly matches patient genetic code, reducing any potential rejection. Interleukin-2 is co administrated during NK cell treatment to improve effectiveness.

Methodology:

The day that patient receive first NK cell infusion is called day 0. The days before are called minus days (-D). Conversely, the days after NK cell infusion are called plus days (+D).

Study administration

* After standard chemotherapy treatment against acute myeloid leukemia (AML) and restoration of haematologic normal levels, patients will receive a 60mg/kg of cyclophosphamide (day -6) and five daily intravenous cycles 25 mg/m2 of the chemotherapic fludarabine every day (day -5, -4, -3, -2, -1).
* Day 0 will be settled from 24h to 48h after fludarabine treatment completion. NK cells will be intravenous administered twice (day 0 and day 7). The first dose of NK cells (day 0) will contain up to 5x10\^7 cells/kg with immunophenotype NK (CD3-CD56+). The second dose might be higher (up to 5x10\^8 cells/kg) in case of no treatment related toxicity after first NK injection. In any case, no more than 1x10\^6 cells/kg with an immunophenotype T (CD56-CD3+) will be administrated.
* From day 0, IL-2 1x10\^6 UI/m2 subcutaneous will be administrated three times a week during two weeks.

Study visits

Before and after the treatment a bone marrow aspirate will be analyzed in order to evaluate minimal residue disease (cytology, cytometry and/or molecular studies) at least one month after NK injection. objective response rate will be reevaluated at least once a year.

Before treatment starts:

* Birthday, gender and personal medical history will be recorded
* physical examination, including measurement of the vital signs (temperature, heart and breathing rate, etc...)
* Blood and urine test
* Bone marrow aspirate in order to evaluate the basal disease

On every visit

* Physical examination and vital signs will be recorded
* Adverse event form
* Other concomitant drugs

After NK treatment

* It will be 11 visits on days +30, +60, +90, +180, +270, +360, +480, +600, +720, +900, +1080 which included a blood and urine test and Lansky/karnofsky scale.
* Additionally on days +30, +360, +720 and +1080 a bone marrow aspirate will be performed to evaluate relapse.

Length of the study:

Up to 35 AML patients will be included in the study during a 32 months recruitment period with a patient follow-up of thirty-six months. The maximum length of the study will be six years.

NK Cells as Consolidation Therapy of Acute Myeloid Leukemia in Children/Adolescents

NK Cells Infusion as Consolidation Treatment of Acute Myeloid Leukemia in Children and Adolescents

Relapse-free rate according to the clinical guidelines. A bone narrow aspirate one month after NK cell infusion will be evaluated for cytomorphological criteria and minimal residue disease (cytometry or real time PCR). Relapse defined as myeloid blast bone marrow presence with the same diagnosis markers, new ones or mixed. From cytologic analysis 25% of blast or minimal residue disease by cytometry (0,01%) and/or molecular level (0,0001%) present at diagnosis with or without cytogenetic alterations.

Relapse-free rate according to the clinical guidelines. A bone narrow aspirate one month after NK cell infusion and at least once a year during the three-year follow-up will be evaluated for cytomorphological criteria and minimal residue disease (cytometry or real time PCR). Relapse defined as myeloid blast bone marrow presence with the same diagnosis markers, new ones or mixed. From cytologic analysis 25% of blast or minimal residue disease by cytometry (0,01%) and/or molecular level (0,0001%) present at diagnosis with or without cytogenetic alterations.

All adverse events (AE) will be monitorized. AE of special interest: administration issues, infections, immunological/allergic/toxic reactions and concomitant drug interactions. AE will be classified according to the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTC) v4.0 criteria or MedDRA classification (mild, moderate, severe or life threatening ).

Donor HLA phenotype will be determined by SS-PCR. The aim is identify KIR ligand mismatch between donor and recipient to achieve better response. Ideally we will choose KIR ligand mismatch recipient donor pair (http://www.ncbi.nlm.nih.gov/pubmed/26341478).

Patient HLA phenotype will be determined by SS-PCR. The aim is identify KIR ligand mismatch between donor and recipient to achieve better response. Ideally we will choose KIR ligand mismatch recipient donor pair (http://www.ncbi.nlm.nih.gov/pubmed/26341478).

The objective is to identify activating KIRs and B haplotype (cen B), by PCR. Ideally we will choose B haplotype donors (http://www.ncbi.nlm.nih.gov/pubmed/20581313)

Chimerism after NK cell infusion by PCR or flow cytometry: to correlate with NK survival and expansion and with clinical outcome (http://www.ncbi.nlm.nih.gov/pubmed/26772158).

Ligand expression of the activatory (MICA, MICB and ULBPs) or inhibitory (HLA-1) receptors of the NK cells will be determined by multiparametric flow cytometry in order to determine the main variables to predict treatment effectiveness and safety.

In vitro allogenic NK cytotoxic activity against leukemic blast will be performed by real time Eur-TDA fluorescence (Blomberg et al. J Immunol Methods 1986).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Consolidation Whole Abdominal Intensity-Modulated Radiation Therapy (IMRT) in Advanced Ovarian Cancer	NCT01180504	Ovarian Cancer Tubal Carcinoma Primary Periton...	intensity-modul...	18 Years -	University Hospital Heidelberg
NK Cells as Consolidation Therapy of Acute Myeloid Leukemia in Children/Adolescents	NCT02763475	Acute Myeloid L... Leukemia Myeloid Leukemi...	cyclophosphamid... Fludarabine NK cell infusio... IL-2	- 21 Years	Instituto de Investigación Hospital Universitario La Paz
Consolidation Whole Abdominal Intensity-Modulated Radiation Therapy (IMRT) in Advanced Ovarian Cancer	NCT01180504	Ovarian Cancer Tubal Carcinoma Primary Periton...	intensity-modul...	18 Years -	University Hospital Heidelberg

Spots Global Cancer Trial Database for consolidation treatment