Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Anti-Infective Agents

All Drugs and Chemicals

Plerixafor

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

They will receive Plerixafor (240 µg/kg/day subcutaneously for 1 dose) on Day 0 at 8 am

Plerixafor (Mozobil)

They will receive G-CSF (5 µg/kg/day) for 4 days (Days -4,-3,-2,-1 at 8 am) followed by Plerixafor (240 µg/kg/day subcutaneously for 1 dose) on Day 0 at 8 am

Plerixafor + G-CSF

Stephen Couban

Stem cells can be transplanted from a healthy donor to a patient to combat blood cancers and other disorders. This process is called stem cell transplantation. Stem cells normally live in the bone marrow. A bone marrow transplantation (BMT) is when the bone marrow is directly transplanted into a patient. However, stem cells can also be stimulated to move from the bone marrow to the blood where they can be collected, a process is called mobilization. When these stem cells are transplanted it is called peripheral blood stem cell transplantation (PBSCT). Both stem cell sources are used for different reasons, but PBSCT is much more common.

There is considerable debate as to which stem cell source, BMT or PBSCT, is optimal. There are differences between the two sources in important transplant outcomes. The stem cell product that is transplanted, also called the stem cell graft, contains more than just stem cells. Results from studies suggest that the variation in the cells with grafts may account for the variation in outcomes. Preliminary data from a recent study conducted by the Canadian Blood and Bone Marrow Transplant Group has associated relative frequencies of particular cell populations with leukemic relapse and another important outcome called graft versus host disease (GVHD). While the later essentially equates to a failed transplant, the former is the most common and devastating complication of stem cell transplantation.

The only drug used to mobilize stem cells into the blood of health donors for collection is G-CSF. However there is a new mobilization drug recently approved called plerixafor. This drug is able to mobilize stem cells when G-CSF has failed and pre-clinical studies suggest that it may produce a superior stem cell graft to G-CSF alone. There is little information available, besides safety and efficacy data, about the effects that plerixafor has on the stem cell graft of normal healthy donors.

This study will compare the stem cell graft in normal healthy donors following plerixafor mobilization versus plerixafor and G-CSF mobilization. Specifically, they will look at the cell populations that have been previously correlated with important transplantation outcomes like relapse and GVHD. The investigators suspect that the stem cell graft mobilized by plerixafor and G-CSF will provide a superior graft to that mobilized by plerixafor alone.

Background:

Stem cell transplantation (SCT) involves transfusing stem cells collected from 3 potential sources: bone marrow, peripheral blood, or umbilical cord. There are 2 major types of transplantation. Autologous SCT involves transplanting the patients own stem cells, while allogeneic transplantation involves transplanting stem cells from someone else. Whatever the source, the transplanted stem cell product is called the graft. Currently, the most common source is peripheral blood, However, there is considerably debate as to the optimal stem cell source because different sources have been associated with different transplant outcomes. One key outcome is graft versus host disease (GVHD). This is the most common complication of SCT and contributes significantly to transplant morbidity and mortality, as well as relapse.

Stem cells normally populate the bone marrow. Drugs are used to encourage stem cells to go into the peripheral blood, a process call mobilization. In the peripheral blood stem cells can be collected and subsequently transplanted. In Canada, the only drug used to mobilize stem cells from donors is filgrastim, a form of granulocyte colony stimulating factor (G-CSF). Although well tolerated, there are some shortcomings to this agent and there is clearly room to improve in terms of the donor experience and providing the optimal stem cell graft.

A soon to be completed study conducted by the Canadian Blood and Bone Marrow Transplant Group (CBMTG), called CBMTG 0601, is evaluating the best stem cell source. The study is aimed to compare the outcomes between allogeneic transplant patients who receive either G-CSF stimulated bone marrow or peripheral blood. This will be a seminal study that should provide valuable information as to the optimal stem cell source in allogeneic SCT. Early results suggest that the investigators may be able to predict important SCT outcomes, such as transplant related mortality, relapse or graft versus host disease, by looking at cell populations in the graft.

Plerixafor is a new mobilization agent that is approved for use in combination with neupogen in myeloma and relapsed lymphoma who are undergoing an autologous SCT. Following numerous publications on the safety and dosing of plerixafor, there were 2 pivotal high quality studies performed in this patient population. The results of this study lead to FDA approval, and Health Canada approval is close. Plerixafor may be a clinically superior mobilizing agent to Neupogen. More importantly though, it has a formidable safety profile and arguably superior in this respect. There has also been a case report and a trial demonstrating both the safety and efficacy of plerixafor in healthy donors as well. Finally, preclinical work suggests that plerixafor mobilization may yield a superior graft. Taken together, this work supports the notion that plerixafor may be a superior mobilization agent over neupogen.

Rationale:

Considering the shortcomings of neupogen and the demonstrated potential of plerixafor in trials with autologous SCT patients, it would be logical to further investigate the efficacy of plerixafor in normal healthy donors for allogeneic SCT. The investigators can confidently state that plerixafor is safe. Furthermore, plerixafor can mobilize myeloma and lymphoma patients who have failed neupogen mobilization. However, although suggested in preclinical data, there is no firm evidence to suggest that plerixafor mobilization provides a superior stem cell graft. The investigators will administer either plerixafor or plerixafor and neupogen then compare the cell populations in both peripheral blood and bone marrow..

Importance:

The use of SCT has steadily increased in the last 20 years. This has especially increased since using neupogen to mobilize stem cells thereby making transplants easier. Now that there is a new agent available that is likely safer and perhaps more efficacious, its use may improve both donor experience and patient outcomes. If plerixafor grafts consist of cell populations that are associated with superior transplant outcomes as determined in CBMTG 0601, then it will likely be used in an upcoming larger clinical trial comparing neupogen and plerixafor in normal healthy donors.

Objectives:

Our primary objective is to determine the best timing for harvesting stem cells from normal donors given plerixafor with or without neupogen. A secondary objective is to evaluate and compare the change over time after plerixafor with or without neupogen administration on the population of cells in the graft predicted to give superior transplant outcomes. The other secondary objective is to evaluate and compare the change over time after plerixafor with or without neupogen administration on the concentration of cells in the PB and BM of normal donors predicted to give GVHD or relapse. The investigators hypothesise that plerixafor with neupogen will provide a graft with increased cell populations associated with superior SCT outcomes.

Healthy Donor Study II - Comparing Plerixafor With G-CSF and Plerixafor

A Pilot Study To Design a Clinical Trial That Will Compare the Ability of Plerixafor Alone Versus Plerixafor Plus G-CSF To Generate a Bone Marrow Versus Blood Transplant Product In Normal Healthy Adults

The frequency of CD34+ and CD34+CD38- cells in a graft has been show to be an excellent measure of hematopoietic engrafting potential.

Relative frequencies of CD56bright NK cells, CD4+ central memory T-cells, perforin+ CD8+ T-cells, and CD19+ CD27-TLR9+ B-cells has been associated with GVHD.

A high frequency of CD56bright NK cells in the stem cell graft has been associated with low leukemia relapse.

Genzyme, a Sanofi Company

Hematologist

Nutritional and Metabolic Diseases

Digestive System Diseases

Metabolic Diseases

Hepatic Insufficiency

Liver Failure

Hematinics

Liver Extracts

Raymond Reding, Md-PhD

Evaluate the outcome of pediatric living donor liver transplantation (LDLT) regarding portal vein reconstruction, ABO-compatibility and impact of maternal donation on graft acceptance.

Data from 250 pediatric LDLT recipients (and their donors), transplanted at Cliniques universitaires Saint-Luc between July 1993 and June 2012, were collected retrospectively using electronic data files. Results were analysed according to ABO matching and portal vein complications. Uni- and multi-variate analysis was used to study the impact of immunosuppression, gender match and maternal donation on acute rejection rate.

Living Donor Liver Transplantation in Children

Living Donor Liver Transplantation in Children: Surgical and Immunological Results in 250 Recipients at Université Catholique de Louvain.

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

COVID-19

Neoplastic Cells, Circulating

Neoplasm Metastasis

Neoplastic Processes

The first cohort of patients to be enrolled for this study will be adults (males and females) with histological proven solid tumors of any stage, seen for routine cancer care at participating community cancer clinic sites. Patients on clinical trials with experimental study drugs will be allowed to participate in this observational prospective study.

Healthy volunteers make up the second, smaller study population for this observational biospecimen laboratory study. Healthy volunteers serve primarily to aid in the proficiency, quality control and/or optimization of study procedures, experimental design assay development, and for device/equipment validation.

Due to the COVID-19 pandemic and the consequent amendment to aid in the research response, study subjects with COVID-19 disease may participate in all aspects of this protocol, but depending on their disease state, infection timeline, and age, participation may be limited to only one component, procedure, and/or type of biospecimen collection. Age is a very important criteria, as pediatric subjects (5-17 years old) will only be eligible to participate in minimally invasive biospecimen collection procedures.

John Powderly, MD

Shruty Lakdawala, MD

Camila Vedia, BS

Primary Objective:

This is a study to investigate the feasibility of harvesting, expanding, and selecting T lymphocytes from cancer patients and healthy volunteers. The preliminary objective of this study is aimed at selecting PD-1+ and CTLA4+ T cells and other cellular fractions from peripheral blood of cancer patients and healthy volunteers by using specific conjugated antibodies, evaluating their functional ex vivo anti-tumor cytotoxicity against targeted autologous tumor cells.

Peripheral whole blood, immune cells, circulating tumor cells, discarded tissue obtained from biopsies and fluid (paracentesis, pleuracentesis), plasma-leukapheresis products, saliva, urine and stool.

A Biospecimen Collection Study of Leukapheresis-Derived Circulating Tumor Cells, Immune Cells, and Progenitor Cells.

A Biospecimen Collection Study to Facilitate Development of an Ex-Vivo Device Platform for Culture, Immune Assay, and Biobanking of Leukapheresis-Derived Circulating Tumor Cells, Immune Cells, and Progenitor Cells.

BioCytics, Inc.

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Patients with suspected prostate cancer (MRI or digital rectal examination), or prostatic hyperplasia with a PSA level\> 4 ng / ml

Male from 50 to 70 years old with a PSA level \<4 ng / mL

A blood sample and a urine sample after prostate massage will be carried out at baseline

Urine sampling

Sandra NESPOULOUS

Antonin MORILLON, PhD

Marie-Emmanuelle LEGRIER, PhD

Yves ALLORY, MD PhD

Constitution of a biological collection within the framework of the establishment of a diagnostic, prognostic and active surveillance test for prostate cancer from long non-coding RNA biomarkers, in 3 cohorts of patients, with cancer of the prostate, with suspected cancer without biopsy confirmation or with prostatic hyperplasia and healthy donors.

This biological collection will also be used as a support for further researches on the identification of biomarkers and genetic markers to improve the prognosis and diagnostic management of patients with prostate pathologies.

Multicenter, RIPH 2 study, evaluating on 3 patient cohorts the feasibility of setting up a diagnostic test, prognosis and active surveillance of prostate cancer using long non-coding RNA biomarkers.

For patients agreeing to participate in the study and having signed a consent form, during their routine care consultation in the urology department, will have a blood sample and a urine sample after prostate massage as part of the study, and if necessary, a tissue sample as part of the treatment.

Patients with prostate cancer will be followed as part of their care at least annually, and their follow-up data will be collected as part of the study, without additional sampling.

A blood sample and a urine sample after prostate massage will be carried out during a single consultation at the CIC Henri Mondor for

3 cohorts of 118 patients in the aim to have 90 evaluable participants will be included in the study:

* 40 patients with prostate cancer, or
* 40 patients with suspected cancer without confirmation on biopsy, or with hyperplasia of the prostate and
* 38 healthy donors.

Prostate cancer or suspicion of prostate cancer

Comparative Study of Diagnostic and Prognosis Biomarkers of Prostate Cancer in Liquid Biopsy

Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.

Criteria will be a minimum of 10ng of total RNA extracted per sample total RNA sequencing and greater than 10 million unique reads mapping to the Gencode V32 reference genome.

Institut Curie

Syndrome

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Hematologic Diseases

Bone Marrow Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

MGTA-145 in combination with plerixafor followed by apheresis on one or two consecutive days

MGTA-145 will be be administered as an IV infusion

MGTA-145

Steven Devine, MD

This research study tests a new medicine for mobilizing stem cells so they can be collected and used for allogeneic stem cell transplant for treatment of hematological malignancies. MGTA-145, the new medicine, will be given with plerixafor.

This is a Phase II, open-label, multicenter, prospective study of MGTA-145 + plerixafor mobilized HLA-matched sibling and matched unrelated donor allografts for myeloablative hematopoietic stem cell transplantation (HSCT) in recipients with hematological malignancies. Donors will undergo 1 or 2 days of mobilization and apheresis.

MGTA-145 + Plerixafor in the Mobilization of HSCs for Allogeneic Transplant in Hematologic Malignancies

A Phase II Study Evaluating the Safety and Efficacy of MGTA-145 in Combination With Plerixafor for the Mobilization and Transplantation of HLA-Matched Donor Hematopoietic Stem Cells in Recipients With Hematological Malignancies

To assess the efficacy of MGTA-145 in combination with plerixafor in mobilizing adequate number of hematopoietic stem cells (≥ 2.0 x 10\^6 CD34+ cells/kg) in healthy donors in one apheresis setting.

To determine the proportion of donors whose cells can be successfully mobilized and collected with a target CD34+ cell dose of at least 4.0 x 10\^6 CD34+ cells/kg actual recipient weight in one apheresis collection

To ascertain the incidence of adverse events (AEs) before and during apheresis experienced by donors receiving MGTA-145 + plerixafor

To ascertain the severity of adverse events (AEs) before and during apheresis experienced by donors receiving MGTA-145 + plerixafor

To determine the incidence of and kinetics of neutrophil and platelet recovery after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor

The proportion of participants with primary and secondary graft failure after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor

To determine the incidence and severity of acute and chronic graft versus host disease (GVHD) after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor

To determine the proportion of treatment-related mortality and disease relapse/progression after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor

To determine the probability of progression-free survival after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor

To determine the probability of overall survival after transplantation of hematopoietic cells mobilized with MGTA-145 + plerixafor

To characterize the adverse effects experienced by recipients receiving grafts mobilized by MGTA-145 + plerixafor

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Healthy Donor Study II - Comparing Plerixafor With G-CSF and Plerixafor	NCT01403896	Malignant Lymph...	Plerixafor (Moz... Plerixafor + G-...	18 Years - 30 Years	Nova Scotia Health Authority
Living Donor Liver Transplantation in Children	NCT02124382	Pediatric Liver... Healthy Donors		- 57 Years	Cliniques universitaires Saint-Luc- Université Catholique de Louvain
A Biospecimen Collection Study of Leukapheresis-Derived Circulating Tumor Cells, Immune Cells, and Progenitor Cells.	NCT00571389	Solid Tumor, Ad... Healthy Donors COVID-19 Donors		5 Years -	BioCytics, Inc.
Comparative Study of Diagnostic and Prognosis Biomarkers of Prostate Cancer in Liquid Biopsy	NCT05141383	Prostate Cancer Healthy Donors	Urine sampling	50 Years - 70 Years	Institut Curie
MGTA-145 + Plerixafor in the Mobilization of HSCs for Allogeneic Transplant in Hematologic Malignancies	NCT04762875	Related Donors ... Healthy Donors Acute Myelogeno... Acute Lymphobla... Myelodysplastic...	MGTA-145 Plerixafor	18 Years - 65 Years	Ensoma
MGTA-145 + Plerixafor in the Mobilization of HSCs for Allogeneic Transplant in Hematologic Malignancies	NCT04762875	Related Donors ... Healthy Donors Acute Myelogeno... Acute Lymphobla... Myelodysplastic...	MGTA-145 Plerixafor	18 Years - 65 Years	Ensoma
Healthy Donor Study II - Comparing Plerixafor With G-CSF and Plerixafor	NCT01403896	Malignant Lymph...	Plerixafor (Moz... Plerixafor + G-...	18 Years - 30 Years	Nova Scotia Health Authority
A Biospecimen Collection Study of Leukapheresis-Derived Circulating Tumor Cells, Immune Cells, and Progenitor Cells.	NCT00571389	Solid Tumor, Ad... Healthy Donors COVID-19 Donors		5 Years -	BioCytics, Inc.

Spots Global Cancer Trial Database for healthy donors