Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Blood and Lymph Conditions

Immune System Diseases

Breast Neoplasms

Neoplasm Metastasis

Lung Neoplasms

Lymphopenia

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Blood samples must be made within 48 hours after the inclusion of the patient. Patients are treated according to the standards of the centre where they are supported. No follow-up is provided in this study.

For each patient, the following analyses is performed:

* The analysis of TCR and BCR repertoire diversity,
* The phenotypic analysis of immune subpopulations,
* The analysis of the global lymphopenia or subpopulations T,
* The analyses by multiplex assay of a large panel of plasma cytokines and chemokines.

Breast cancer cohort

Lung cancer cohort

Olivier TREDAN, MD

The T and B cells repertoire diversity represent one of the immune defence level which controls the integrity of the organism and determines its ability to recognize and control infectious attacks and development of tumours. The study of the lymphocytes TCR and BCR diversity could permit to better understand how lymphopenia act on overall survival and to improve detection of high risk patients who could benefit of adapted therapies for better care.

The therapeutic management recommendations of patients with metastatic cancer offer standard treatment in specific situations. But, there is always a subgroup of patients who do not benefit from treatment and which has a very low survival. The risk of death for patients is very variable depending on the initial cancer site, tumor aggressiveness and chemosensitivity of tumours.

It's therefore important to have relevant prognostic tools to predict such an excess of relative toxicity or drug resistance. Simple prognostic factors for survival as the performance status (PS) have already been highlighted in several studies. Thus, the possibility to identify a group of patients with a higher risk of mortality could be of major interest for clinicians. In fact such stratification will allow:

* To limit this risk by adjusting the therapy and/or associated treatments (antibiotic prophylaxis, dose reduction ...),
* To develop protocols for testing innovative strategies specific to this high risk population.

The objectives of these innovative protocols would be designed to correct lymphodivpenia.

The main objective is to show that T divpenia (low TCR combinatorial diversity \<30%) is a risk factor for early death after chemotherapy (early death: any death occurring within 3 months (lung cancer) or within 6 months (breast cancer) after the start of chemotherapy).

The secondary objectives are:

* To establish that the divpenia factor is independent of clinical and biological prognostic factors (PS, LDH, haemoglobin, lymphopenia or ANC) to predict a early death,
* To establish that the prognostic score NDL which will combine in a two-dimensional graph the CD4 count or total lymphocytes count and TCR repertoire diversity will allow a better stratification of lympho-divpenic patients who will benefit from more appropriate treatments,
* To characterize other circulating markers this could improve the identification of the early death risk (phenotypic markers, cytokines ...) in combination with the previous settings.

Prognostic models have been established in many tumor types at the initial stage or at time of the relapse (breast and lung cancers ...). It seems necessary to highlight other clinical and biological prognostic factors that would estimate a lower survival at 6 months, whatever the nature or the original site of the tumour.

The strong prognostic value of lymphopenia in the early death after chemotherapy or hematologic toxicity of chemotherapy has recently been established in several tumor models. 25% of patients with metastatic solid cancers have a systemic immune dysfunction.

Further analysis incorporating prior any treatment (D0) a systematic phenotypic analysis of lymphocyte subpopulations in the patients' blood showed that a significant reduction in the absolute number of peripheral CD4+ T cells (\<450/μl) was an independent factor risk of early death and febrile neutropenia in patients with solid cancers of different origin (lymphoma, myeloma, sarcoma, breast cancer) treated with chemotherapy.

However, early death remains rare events and a more recent study has established that a lymphopenia (\<1000 lymphocytes/µl) was an independent prognostic factor for overall survival in patients with solid tumours.

Recent studies have shown the importance of combinatorial diversity of T and B lymphocytes repertoire (TCR/BCR) in the efficiency of the immune response against infection.

A preliminary analysis of TCR repertoire diversity, in a retrospective cohort of patients with metastatic breast cancer, demonstrated the independent predictive value of divpenia for overall survival in these patients. This research has demonstrated that patients with cancer had a very large disparity in immune TCR diversity and that it was not always correlated with lymphocyte count.

These preliminary data show that the discriminating power of TCR diversity is greater than the measurement of cell count. The combined analysis of these data in a NDL® graph may help to better discriminate patients at risk for which it is necessary to develop new therapeutic strategies.

Prognostic Value of Divpenia and CD4 Count in Relapsed Breast or Lung Cancer Patients

Study of Prognostic Value of T Cell Receptor Diversity and CD4 Lymphopenia in First Relapse Breast or Lung Cancer Patients

To show that T divpenia (low TCR combinatorial diversity \<30%) is a risk factor for early death after chemotherapy (early death: any death occurring within 3 months (lung cancer) or within 6 months (breast cancer) after the start of chemotherapy).

Establish that the divpenia factor is independent of clinical and biological prognostic factors (PS, LDH, initial metastasis localization, Hb, PMN, age, sex) to predict a early death,

Establish that the prognostic score NDL which will combine in a two-dimensional graph the CD4 count or total lymphocytes count and TCR repertoire diversity will allow a better stratification of lympho-divpenic patients who will benefit from more appropriate treatments

Characterize other circulating markers this could improve the identification of the early death risk (phenotypic markers, cytokines ...) in combination with the previous settings

The Biostatistics and Therapy Evaluation Unit

BEC (Department of Clinical Sciences)

Centre Leon Berard

Digestive System Diseases

Carcinoma

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Leukopenia

Cytopenia

Hematologic Diseases

Leukocyte Disorders

Syndrome

Immunologic Deficiency Syndromes

Hematinics

All Drugs and Chemicals

Liver Extracts

Immunosuppressive Agents

A total of 145 Liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) were retrospectively enrolled at Kaohsiung Chang Gung Memorial Hospital between 2006 and 2019. Clinical records from 7 days before LT (pre-LT) to 1 year after LT (post-LT) were analysed. In a prospective study from March 2022 to June 2023, 20 lymphopenia and 25 non-lymphopenia HCC recipients were enrolled, and a phenotypic analysis of peripheral blood lymphocytes was performed using multiparameter flow cytometry.

A total of 145 Liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) were retrospectively enrolled at Kaohsiung Chang Gung Memorial Hospital between 2006 and 2019. Clinical records from 7 days before LT (pre-LT) to 1 year after LT (post-LT) were analysed including overall survival, recurrence-free survival, association between clinical parameter with mortality, patient characteristics by pre-lymphopenia and post-lymphopenia levels and lymphocyte status of HCC patients with usage of different immunosuppressants. In prospective study from March 2022 to June 2023, 20 lymphopenia and 25 non-lymphopenia HCC recipients were enrolled, and a phenotypic analysis of peripheral blood lymphocytes was performed using multiparameter flow cytometry to identify the major immune cell subsets and the characteristics of patients in the prospective cohort between pre-LT lymphopenia and non-lymphopenia groups.

Persistent Lymphopenia in Liver Transplantation and Its Molecular Insights for Hepatocellular Carcinoma

Persistent Lymphopenia as a Prognostic Indicator in Liver Transplantation and Its Molecular Insights for Hepatocellular Carcinoma Recipients

The clinical records of 145 patients with HCC from seven days pre-LT to one-year post-LT illustrated that the longitudinal values of lymphocytes were persistently low in patients with peritransplant high neutrophil lymphocyte ratio, indicating a significant decrease in survival rate when compared to other patients.

A significant decrease in cell counts and percentage of overall T cells in the peritransplant lymphopenia group. In particular, the counts of T cell subsets, T helper cells, and cluster of differentiation 8 (CD8+) cytotoxic/activated T cells significantly decreased in the peritransplant lymphopenia group with all of their naïve, effector, and memory forms.

In the subset of 116 of 145 HCC recipients (80%) who did not experience or recover from lymphopenia, no significant associations were observed with immunosuppressant use. Surprisingly, HCC recipients with long-term peritransplant lymphopenia exhibited a significant association with increased sirolimus use (p = 0.024) and decreased tacrolimus use (p = 0.001), whereas those with post-LT lymphopenia showed no association with the use of different immunosuppressants.

Chang Gung Memorial Hospital

Disease Progression

Breast Diseases

Skin Diseases

Immunomodulating Agents

the patients will receive Placebo before the 1st and during the 3rd CT cycle (N=6)

patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle and the placebo during the 3rd CT cycle (N=6)

patients will receive the placebo before the 1st CT cycle and a delayed treatment with CYT107 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (N=6)

patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle and a maintenance cycle of IL-7 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (N=6).

Placebo before the 1st (D0, D7, D14)and during the 3rd CT cycle (D57, D64, D71)

placebo

patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle (D0, D7, D14) and the placebo during the 3rd CT cycle (D57, D64, D71)

interleukin 7

patients will receive the placebo before the 1st CT cycle (D0, D7, D14) and a delayed treatment with CYT107 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (D57, D64, D71)

patients will receive an induction cycle of CYT107 (10µg/kg/week subcutaneously for 3 weeks) before the 1st CT cycle (D0, D7, D14) and a maintenance cycle of IL-7 (10µg/kg/week subcutaneously for 3 weeks) during the 3rd CT cycle (D57, D64, D71)

Isabelle Ray Coquart

The purpose of the study is to evaluate the impact of an immunotherapy by IL-7 on CD4 lymphopenia, risks of severe haematological toxicity and tumor progression in metastatic breast cancer patients.

The primary objective is to determine the optimal schedule to deliver CYT107 during chemotherapy based on restoration of CD4 count.

This study is a phase II, randomised, double-blind, placebo-controlled, single-centre.

24 patients will be included in the study.

A key secondary objective is to determine if CYT107 treatment enables to reduce the incidence of severe haematological toxicity (any type of haematological toxicity Grade ≥ 3) post-chemotherapy.

Other secondary objectives are to assess the impact of CYT107 treatment on the following parameters:

* Overall incidence of side effects (any type any grade)
* Progression-free survival (PFS)
* Compliance to chemotherapy regimen (dose intensity, number of chemotherapy cycles).
* CD4 lymphopenia over the study period

Exploratory biological markers

A series of biomarkers analyses will be performed to evaluate if CYT107 treatment will:

* selectively stimulate the proliferation and activation of peripheral immune subsets (analysis of phenotype and activation status of peripheral immune e sub-populations)
* selectively improve the functional response of T cells, DC subsets and NK cells.
* is able to revert tolerogenic immune burden to increase specific anti-tumor response (measure of antigen specific CD8 response, measure of cytokine plasmatic levels)
* enable to increase TCR diversity (analysis of combinatorial diversity).

Study Evaluating Impact of IL-7 on CD4 Lymphopenia, Risks of Severe Haematological Toxicity and Tumor Progression in Metastatic Breast Cancer Patients

A Randomised, Multicentric, Phase 2a Study Evaluating the Impact of an Immunotherapy by IL-7 on CD4 Lymphopenia, Risks of Severe Haematological Toxicity and Tumor Progression in Metastatic Breast Cancer Patients

Evolution of CD4 count from Day 0 to Week 11 with repeated measures from D0 to W12 (D0, D21, D57, D78).

Time from randomisation to first evidence of progression or death of any cause.

Number of CT cycles, CT dose delays and/or reduction, CT discontinuation

Evolution of CD4 count from Day 0 to end of study visit

Measure of frequency and activation status of circulating immune subpopulations on fresh whole blood. Multi-parametric marker sets (6-8 markers) will be used to analyse phenotype of immune subpopulations (TCD4+, TCD8+, Treg, T, NK, DC) and their activation status (PD1, ICOS, CD39, CD73, CD62L, CCR7, CD45RO, CD45RA, CD86).

Analysis of the functional response of T cells, DC subsets and NK cells

* Analysis of tumor associated antigen (TAA) specific CD8 responses
* Quantification of circulating cytokines including mainly, but not limited to, IL-6, IL-2, IFN, VEGF, TNF, IL-15,F FGF using Luminex technology and VEGF, TGF, IL-7R by Elisa.

Evaluation of T cell receptor diversity using ImmuneTraCkeR test and Constel'ID software (ImmunID Technologies, Grenoble, France).

Number of patients with AEs (any type any grade) using NCI-CTCAE scale (version 4.0) from D0 to W12

Ministry of Health, France

Cytheris, Inc.

Rare Diseases

Esophageal Neoplasms

Head and Neck Neoplasms

Esophageal Diseases

Esophageal Cancer

Vaccines

30 participants currently receiving, planning to receive, or recently completed chemoradiation for esophageal cancer. This group will be subdivided into Group 1A, which will comprise 15 participants treated with proton therapy, and Group 1B, which will comprise 15 patients treated with intensity modulated radiation therapy (IMRT).

30 participants currently receiving, planning to receive, or recently completed chemoradiation for hepatocellular carcinoma. This group will be subdivided into Group 2A, which will comprise 15 participants treated with proton therapy, and Group 2B, which will comprise 15 patients treated with intensity modulated radiation therapy (IMRT).

Pneumonia vaccine

Steven H Lin, MD

To learn how radiation treatment may affect your responses to vaccines against pneumonia.

Primary Objectives

- Determine the impact of Grade IV radiation-induced lymphopenia on serologic responses to pneumococcal vaccination.

Secondary Objectives

* Determine the impact of chemoradiation on serologic responses to pneumococcal vaccination.
* Determine the impact of radiation modality on serologic responses to pneumococcal vaccination.
* Determine the impact of radiation modality on systemic immunity.
* Determine the incidence of pneumonia among patients treated with a pneumococcal vaccine.
* Determine the impact of radiation modality on pathologic response.
* Determine the impact of radiation modality on intratumoral immunity.
* Determine the relationship between changes in systemic and intratumoral immunity and clinical outcomes (i.e., incidence of pneumonia and pathologic response)
* Determine the impact of tumor histology on serologic responses to pneumococcal vaccination.

Serologic Response to Pneumococcal Vaccination Among Esophageal Cancer Patients With High Grade Lymphopenia After Chemoradiation

Serologic responses will be calculated as the average fold change in antibody titer for each of 20 pneumococcal serotypes between baseline (time 0) and the first post-vaccination blood draw.

M.D. Anderson Cancer Center

Infections

Communicable Diseases

Thoracic Diseases

Central Nervous System Depressants

Anesthetics

Post operative infections and their association with lymphopenia are assessed in this study for patients over 18 years of age undergoing digestive or thoracic cancer surgery under general anesthesia.

Lymphocytes counts are obtained from patients undergoing pulmonary or digestive cancer surgery. The rates are assessed before surgery (day 0) and at days 1, 3, 5 and 8 after surgery. Anesthetic and surgical procedures are collected as well as risk factors for postoperative infections recognized in the literature. Clinical and biological signs of infection are collected.

Collection of plasma cell rate

Serge Molliex, PhD

Postoperative infections are one of the most common complications in thoracic and digestive cancer surgery. Former studies have demonstrated that inflammatory response is altered during peri-operative period causing lymphopenia. It has been suggested that lymphopenia may contribute to postoperative infection. To date, no one has proved it in a multivariate analysis. The aim of this study is to determine if lymphopenia is associated with postoperative infections in thoracic and digestive cancer surgery.

Postoperative infections are one of the most common complications in thoracic and digestive cancer surgery. Former studies have demonstrated that inflammatory response is altered during peri-operative period causing lymphopenia. It has been suggested that lymphopenia may contribute to postoperative infection. To date, no one has proved it in a multivariate analysis.

The aim of this study is to determine if lymphopenia is associated with postoperative infections in thoracic and digestive cancer surgery. It is a multicenter French cohort study. Lymphocytes counts are obtained from patients undergoing pulmonary or digestive cancer surgery before surgery (day-0) as well 1, 3, 5 and 8 days after surgery. Anesthetic and surgical procedures are collected as well as risk factors for postoperative infections recognized in the literature. Clinical and biological signs of infection are collected.

Assessment of Postoperative Lymphopenia as Risk Factor for Postoperative Infections

Assessment of Postoperative Lymphopenia as Risk Factor for Postoperative Infections: EVALYMPH Study

Patients undergoing general anesthesia for thoracic or digestive surgery could present lymphopenia. In this situation, the presence of post operative infection is notified. The correlation between lymphopenia and post operative infections is studied.

To identify anesthetic and surgical parameters influencing postoperative lymphocytes cells count.

Centre Hospitalier Universitaire de Saint Etienne

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroepithelioma

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

Dexamethasone

Temozolomide

Dexamethasone acetate

Patients receive single dose of NT-I7 IM. Treatment continues in the absence of disease progression or unacceptable toxicity. Dose Escalation

Laboratory Biomarker Analysis Correlative Studies

Patients receive single dose Placebo IM (blinded). Patients also on Dexamethasone \</=0.75mg daily Treatment continues in the absence of disease progression or unacceptable toxicity. Pilot

Laboratory Biomarker Analysis Correlative Studies

Patients receive single dose MTD NT-I7 IM determined in Arm A (Blinded) . Patients also on Dexamethasone \<=0.75mg daily Treatment continues in the absence of disease progression or unacceptable toxicity. Pilot

Laboratory Biomarker Analysis Correlative Studies

Patients receive single dose MTD NT-I7 IM determined in Arm B (Blinded) . Patients also on Dexamethasone \>= 4mg daily Treatment continues in the absence of disease progression or unacceptable toxicity. Pilot

Laboratory Biomarker Analysis Correlative Studies

Laboratory Biomarker Analysis

NT-I7

Placebo

Jian L Campian, MD, PhD

The purpose of this study is to determine the maximum tolerated dose (MTD) and select optimal biological doses (OBD) of the study drug NT-I7 in High Grade Glioma patients with severe lymphopenia, as well as to test the effect of NT-I7 on the CD4 counts of patients in comparison to control participants. This study has both a Phase I and Pilot component.

PRIMARY OBJECTIVES:

Phase I: To determine the MTD (Maximum Tolerated Dose) and select optimal biological doses (OBD) of NT-I7 in HGG patients with severe lymphopenia

Pilot Study: To test the effect of NT-I7 on CD4 counts compared to control

SECONDARY OBJECTIVES:

1. To evaluate the optimal biological dose of NT-I7
2. To evaluate the effect of concurrent dexamethasone
3. To evaluate the duration of effect on CD4 counts (up to 6 months)
4. To evaluate the total lymphocyte counts over time and serial T cell lymphocyte subtypes and the effect on T cell repertoire (up to 6 months)
5. To evaluate the serial cytokine levels (up to 6 months)
6. To evaluate the impact of adjuvant temozolomide on NT-I7 effects on CD4 counts
7. To evaluate anti-drug antibodies
8. To evaluate the pharmacokinetic profile of NT-I7 after intramuscular administration in this patient population
9. To evaluate the safety and toxicity of NT-I7 in patients with high grade glioma

OUTLINE: Patients are assigned to 1 of 2 groups depending on their use of dexamethasone.

GROUP A: Patients not on dexamethasone (or equivalent of an alternative corticosteroid), or on a dose lower than a physiologic dose (=\< 0.75 mg daily)

GROUP B: patients who require dexamethasone (or equivalent of an alternative corticosteroid) =\> 4 mg daily

Patients must have been on the group assignment dose of corticosteroids for at least 5 days prior to the dose of NT-I7. Corticosteroid dose changes prior to the start of treatment are allowed as long as they do not alter patient's group assignment.

PHASE I TREATMENT PLAN

All patients (both Groups A and B) will be given a single dose of NT-I7 by intramuscular injection starting at 60 μg/kg, within one week after completing concurrent RT+TMZ and before starting adjuvant TMZ treatment, during the standard post-radiation break. Following this period, as per standard treatment, patients will go on to receive adjuvant temozolomide on Days 1-5 of 28-day cycles for 6 cycles. There should be about six weeks between the study injection and the start of adjuvant temozolomide; thus the start of adjuvant TMZ will be approximately two weeks later than the usual start, which is 4 weeks post-end of radiation. Patients who are delayed from receiving or are not able to receive adjuvant TMZ treatment may continue on study; adjuvant TMZ treatment is not a requirement for participation.

PILOT STUDY TREATMENT PLAN

GROUP A: participants will be given either a placebo (NT-I7 diluent) or one dose of NT-I7 at the Phase I Group A OBD by intramuscular injection within one week after completing concurrent RT+TMZ and before starting adjuvant TMZ treatment, during the standard post-radiation break.

GROUP B: participants will be given one dose of NT-I7 at the Phase I Group B OBD by intramuscular injection within one week after completing concurrent RT+TMZ and before starting adjuvant TMZ treatment, during the standard post-radiation break.

After completion of study treatment, patients are followed up every 2 months for 2 years and then every 6 months thereafter.

Dose Escalation - 3 levels - Group A Dexamethasone less/equal 0.75mg/day; Group B Dexamethasone greater/equal 4mg/day. At MTD Group A - w/outDexamethasone randomized Arm 1 placebo and Arm 2 MTD; Group B MTD w/ Dexamethasone single arm

Participant is blinded and partially randomized in the Pilot study.

Study of the Effect NT-I7 on CD4 Counts in Patients With High Grade Gliomas

A Phase I and Pilot Study of the Effect of rhIL-7-hyFc (NT-I7) on CD4 Counts in Patients With High Grade Gliomas and Severe Treatment-related CD4 Lymphopenia After Concurrent Radiation and Temozolomide

The primary treatment effect is defined as an absolute increase in CD4 counts in patients treated with glycosylated recombinant human interleukin-7 compared to the control group patients without glycosylated recombinant human interleukin-7 at week 6 after radiation treatment + temozolomide treatment.

The optimal dose will be selected based on the highest absolute increase of CD4 counts compared to the control if toxicity profiles are similar between the two dose levels. Otherwise, safety will be the first consideration for dose selection. The results of the two concurrent dexamethasone groups will be summarized with standard descriptive statistics. The dose selection criteria will be similar to the non-dexamethasone groups with priority on safety rather than the highest absolute increase of CD4 counts.

National Cancer Institute (NCI)

NeoImmuneTech

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Glioblastoma

Astrocytoma

Anaplastic Astrocytoma

Fingolimod Hydrochloride

Immunologic Factors

Five evaluable patients with newly diagnosed high grade gliomas who will undergo standard concomitant radiation and temozolomide followed by adjuvant temozolomide will be accrued to this open-label, single arm, safety study. Oral fingolimod will be given 1 week prior to the initiation of concurrent radiation and temozolomide and will be discontinued immediately upon completion of the six weeks of therapy. Fingolimod will be administered at 0.5 mg every day for the first two weeks. Beginning the third week, they will take fingolimod on Monday, Wednesday and Friday until the end of radiotherapy or until the 28th dose, whichever comes first.

Oral fingolimod will be given 1 week prior to the initiation of concurrent radiation and temozolomide and will be discontinued immediately upon completion of the six weeks of therapy.

Fingolimod

Stuart Grossman, MD

A recent prospective multicenter study by Dr. Grossman demonstrated that 40% of patients with high grade glioma undergoing radiation and chemotherapy developed severe and persistent lymphopenia (CD4 counts \<200 cells/mm3). This lymphopenia lasted for twelve months following radiation treatment and on multivariate analysis was associated with shorter survival. Our group has data that strongly suggests that this lymphopenia is secondary to the inadvertent radiation of circulating lymphocytes as they pass through the radiation beam. Investigators propose the use of FDA approved for multiple sclerosis, fingolimod to signal lymphocytes to leave the circulation prior to the initiation of radiation. It is a functional antagonist of the sphingosine-1-phosphate receptor (S1PR) pathway and prevents lymphocyte egress from secondary lymphoid organs.

Oral fingolimod will be given 1 week prior to the initiation of concurrent radiation and temozolomide and will be discontinued immediately upon completion of the six weeks of therapy. The primary objective is to evaluate if fingolimod can be safely combined with radiation and temozolomide. Secondary endpoint is total lymphocyte counts (TLC) for the proposed study participants. Investigators expect that patients receiving radiation and temozolomide plus fingolimod have a recovery of lymphocyte counts to 80% of baseline within four months, reference to historical control in which sustained lymphopenia lasted for twelve months.

Five evaluable patients with newly diagnosed high grade gliomas who will undergo standard concomitant radiation and temozolomide followed by adjuvant temozolomide will be accrued to this open-label, single arm, safety study. Oral fingolimod will be given 1 week prior to the initiation of concurrent radiation and temozolomide and will be discontinued immediately upon completion of the six weeks of therapy.

The primary objective is to evaluate if fingolimod can be safely combined with radiation and temozolomide. This standard chemoradiation causes 40% of patients to develop severe lymphopenia two months after initiation of therapy. Investigators expect that when this is combined with fingolimod, virtually all patients will have severe lymphopenia two months after beginning treatment. Investigators will determine if these patients who routinely receive pneumocystis jiroveci prophylaxis develop other severe opportunistic infections that would prohibit further evaluation of this novel treatment approach. Primary endpoint is incidence of greater than or equal to Grade III infections attributable to fingolimod-induced lymphopenia defined by the NIH/NCI Common Terminology Criteria for Adverse Events (CTCAE) within four months of starting fingolimod.

The secondary objective is to obtain preliminary information regarding the ability of fingolimod to reduce radiation-related lymphopenia three months after stopping fingolimod. The NIH funded Adult Brain Tumor Consortium (ABTC) followed total lymphocyte and CD4 counts in 96 patients after treatment with radiation and temozolomide. The severe lymphopenia (CD4 count less than 200/mm3) lasted for twelve months in this historical control. Secondary endpoint is total lymphocyte counts (TLC) for the proposed study participants. These will be compared with patient level data on TLC from an historical cohort obtained from the ABTC. Investigators expect that patients receiving radiation and temozolomide plus fingolimod have a recovery of lymphocyte counts to 80% of baseline within four months, reference to historical control in which sustained lymphopenia lasted for twelve months.

Investigators will also obtain laboratory analysis on lymphocyte subtypes and cytokine levels (CD3, CD4, CD8, IL-7, TGF-Beta, etc.). Routine care for high grade gliomas includes weekly Heme-8 and absolute lymphocyte count. Research blood will be obtained at 2 weeks prior to chemoradiation and again at weeks 6, 10, 18, 26 and 46. Patients will be on study for approximately one year.

A Safety Study of Fingolimod With Radiation and Temozolomide in Newly Diagnosed High Grade Glioma

Incidence of greater than or equal to Grade III infections attributable to fingolimod-induced lymphopenia defined by the NIH/NCI Common Terminology Criteria for Adverse Events (CTCAE)

Total lymphocyte counts (TLC) for study participants compared to TLC for historical control

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Thrombocytopenia

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Anemia

Neutropenia

Blood Platelet Disorders

Agranulocytosis

Ovarian Cancer

Ovarian Epithelial Cancer

Granulocytopenia

Antihypertensive Agents

Vasodilator Agents

Vasoconstrictor Agents

Gemcitabine

Angiotensin I (1-7)

Angiotensin II

Angiotensinogen

Combination gemcitabine and platinum-based chemotherapy with concurrent placebo

Combination gemcitabine and platinum-based chemotherapy with concurrent 100 ug/kg/day TXA127

Combination gemcitabine and platinum-based chemotherapy with concurrent 300 ug/kg/day TXA127

Once daily subcutaneous injection of 100 ug/kg

TXA127

Once daily subcutaneous injection of 300 ug/kg

Once daily subcutaneous injection of placebo

Gere S diZerega, MD

This research study will investigate the safety and effectiveness of two different dose levels of a new, unapproved drug to be given along with the chemotherapy regimens gemcitabine and carboplatin or gemcitabine and cisplatin prescribed to women for the treatment of ovarian cancer. This experimental drug is called TXA127 and is being tested for effectiveness to see if it will help reduce some of the side effects of the chemotherapy, primarily low blood platelet levels that lead to excess bleeding. This study also intends to test the safety of TXA127 when given as an injection under the skin on a daily basis concurrently with up to 6 cycles of the prescribed chemotherapy.

This is a Phase IIb, multicenter, randomized, double-blind, placebo-controlled study comparing safety and efficacy of two dose levels of TXA127 when administered during 6 cycles of combination gemcitabine and platinum-based chemotherapy. This study intends to investigate the effectiveness of TXA127 for the mitigation of severity and/or incidence of thrombocytopenia, as well as safety when administered as a self-injected, subcutaneous solution.

Females 18 years of age or older with a confirmed diagnosis of ovarian carcinoma who are scheduled to undergo combination chemotherapy with gemcitabine and carboplatin or gemcitabine and cisplatin will be considered for this study. Subjects may be chemotherapy naïve, newly diagnosed, or post a single course of chemotherapy followed by a progression- and treatment-free interval of at least 3 months, or post 2 or more previous courses of chemotherapy after a progression- and treatment-free interval of at least 6 months.

Subjects will be randomized in a 1:1:1 ratio to one of the following three blinded treatment groups: placebo, 100 ug/kg/day TXA127 and 300 ug/kg/day TXA127.

Treatment will be concurrent with up to six consecutive 21-day cycles of one of the following gemcitabine and platin regimens:

Regimen A

* Intravenous cisplatin therapy at a dose of 30-50 mg/m2 given on Day 1 of the cycle
* Intravenous gemcitabine at a dose of 800 mg/m2 given on Day 1 after cisplatin and on Day 8 of the cycle.

Regimen B

* Intravenous gemcitabine at a dose of 1000 mg/m2 given on Days 1 and 8 of the cycle
* Intravenous carboplatin AUC 4 given after gemcitabine on Day 1 of the cycle

TXA127 will be self-administered as a subcutaneous injection by the subject once daily on Days 2-6 and 9-15 during each cycle of chemotherapy. Blood specimens will be drawn for hematologic analysis on Days 1, 8 and 15 of each treatment cycle.

Study of Drug to Reduce Thrombocytopenia in Patients Receiving Chemo for Ovarian, Fallopian Tube or Peritoneal Cancer

Ph IIb Study Evaluating the Safety & Efficacy of TXA127 in the Reduction of Incidence and Severity of Thrombocytopenia in Patients Receiving Combination Gemcitabine and Platinum Therapy for Ovarian, Fallopian Tube, or Peritoneal Carcinoma

Mean percentage of cycles with platelet counts below 50,000/mm3

Number of subjects who experienced a platelet count below 50,000/mm3

Mean percentage of treatment cycles where platelets counts were below 25,000/mm3

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prognostic Value of Divpenia and CD4 Count in Relapsed Breast or Lung Cancer Patients	NCT01306188	Breast Cancer Lung Cancer	Breast cancer c... Lung cancer coh...	18 Years -	Centre Leon Berard
Persistent Lymphopenia in Liver Transplantation and Its Molecular Insights for Hepatocellular Carcinoma	NCT06368349	Lymphopenia		20 Years - 80 Years	Chang Gung Memorial Hospital
Study Evaluating Impact of IL-7 on CD4 Lymphopenia, Risks of Severe Haematological Toxicity and Tumor Progression in Metastatic Breast Cancer Patients	NCT01368107	Metastatic Brea...	placebo interleukin 7 interleukin 7 interleukin 7	18 Years -	Centre Leon Berard
Serologic Response to Pneumococcal Vaccination Among Esophageal Cancer Patients With High Grade Lymphopenia After Chemoradiation	NCT06181656	Pneumococcal Va... Esophageal Canc... Lymphopenia Chemoradiation	Pneumonia vacci...	18 Years -	M.D. Anderson Cancer Center
Assessment of Postoperative Lymphopenia as Risk Factor for Postoperative Infections	NCT02799251	Cancer of the D... Thoracic Diseas...	Collection of p...	18 Years -	Centre Hospitalier Universitaire de Saint Etienne
Study of the Effect NT-I7 on CD4 Counts in Patients With High Grade Gliomas	NCT02659800	Lymphopenia Malignant Gliom...	Laboratory Biom... NT-I7 Placebo	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
A Safety Study of Fingolimod With Radiation and Temozolomide in Newly Diagnosed High Grade Glioma	NCT02490930	Glioblastoma Anaplastic Astr...	Fingolimod	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Persistent Lymphopenia in Liver Transplantation and Its Molecular Insights for Hepatocellular Carcinoma	NCT06368349	Lymphopenia		20 Years - 80 Years	Chang Gung Memorial Hospital
Study of Drug to Reduce Thrombocytopenia in Patients Receiving Chemo for Ovarian, Fallopian Tube or Peritoneal Cancer	NCT00771810	Thrombocytopeni... Neutropenia Lymphopenia Anemia	TXA127 TXA127 Placebo	18 Years -	Tarix Pharmaceuticals

Spots Global Cancer Trial Database for lymphopenia

Every month we try and update this database with for lymphopenia cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for lymphopenia

Every month we try and update this database with for lymphopenia cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for lymphopenia cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.