Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Behaviors and Mental Disorders

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Neoplasms by Histologic Type

Hematologic Diseases

Myeloproliferative Disorders

Bone Marrow Diseases

Chronic Disease

Disease Attributes

Myeloid Leukemia

Quality of Life

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

questionnaire

na xu, doctor

Department of Hematology Nanfang Hospital Southern M University

Successful outcomes in CML require both prolonged adherence to oral TKI therapy by patients and careful monitoring of treatment responses by their physicians. Patient Reported Outcomes(PRO) assessment is important to facilitate decisions in the current treatment landscape of CML.

1. Above 18 years of age.
2. Patient with confirmed diagnosis of Philadelphia chromosome positive and/or BCR-ABL positive chronic myeloid leukemia (CML).
3. Written informed consent.
4. Patients enrolled in investigational drug-trials or other type of clinical trials are also eligible.

A Study for PRO of CML in Real Word

Validation Value of the Questionnaire to Assess Health-related Quality of Life in Patients With CML

Health-related quality of life (HRQOL) assessment in the current treatment landscape of chronic myeloid leukemia

xuna

professor

Immune System Diseases

Syndrome

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Hematologic Neoplasms

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma

Precancerous Conditions

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Lymphocytic Leukemia

Acute Graft Versus Host Disease

Lymphosarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach. Older subjects will receive a lower dose of irradiation to reduce the regimen intensity. Determine appropriate level of post transplant immunosuppression

Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach.

Miltenyi system

Minocher M Battiwalla, M.D.

This study will try to improve the safety and effectiveness of stem cell transplant procedures in patients with cancers of the blood. It will use a special machine to separate immune cells (T cells) from the blood of both the donor and the patient and will use photodepletion, a laboratory procedure that selectively kills cancer cells exposed to light. These special procedures may reduce the risk of graft-versus-host-disease (GVHD), a serious complication of stem cell transplants in which the donor's immune cells destroy the patient's healthy tissues, and at the same time may permit a greater graft-versus-leukemia effect, in which the donated cells fight any residual tumor cells that might remain in the body.

Patients between 18 and 75 years of age with a life-threatening disease of the bone marrow (acute or chronic leukemia, myelodysplastic syndrome, or myeloproliferative syndrome) may be eligible for this study. Candidates must have a family member who is a suitable tissue match.

Peripheral blood stem cell transplant research carried out by the NHLBI BMT Unit focus on approaches in transplant techniques designed to decrease graft versus host disease (GVHD), increase the graft-versus-leukemia (GVL) effect, and/or reduce the risk for post-transplant graft rejection or disease relapse.

Ex vivo selective depletion of alloreacting T cells, hereafter referred as selective depletion (SD), represents a translational strategy aiming to reduce severe GVHD whilst preserving GVL. We found that selectively depleted transplants are safe to administer and associated with less severe acute GVHD. This protocol is designed to evaluate the safety and efficacy of photodepletion (PD) as an improved selective depletion procedure in the HLA-matched peripheral blood stem cell transplant setting and to determine whether post-transplant immunosuppression with cyclosporine is necessary to prevent severe GVHD after a photodepleted transplant.

The protocol will accrue subjects ages 18-75 who are diagnosed with a hematological malignancy where allogeneic stem cell transplantation from an HLA-matched sibling would be normally indicated. Diagnostic categories will include acute and chronic leukemias, myelodysplastic syndromes, B-cell lymphomas, multiple myeloma, and myeloproliferative syndromes.

Participants have a central intravenous (IV) line placed into a large vein. The tube is used for giving the donated stem cells and antibiotics and other medicines, for transfusions of red blood cells and platelets, and for collecting blood samples. Treatment starts with a conditioning regimen of chemotherapy (fludarabine and cyclophosphamide) and total body irradiation to suppress immunity and prevent rejection of the donated stem cells. The day after chemotherapy ends, the stem cells are given through the central line. This is followed by transfusion of the donor's immune cells, which have been treated to remove cells that could cause severe GVHD. Also to minimize the risk of GVHD, patients are given cyclosporine. Not all participants receive the same amount of this drug; in order to determine how much immunosuppression is needed to protect against severe GVHD, the length of treatment with cyclosporine varies among patients, depending on when they entered the study and how well preceding patients did.

The average hospital stay for stem cell transplantation is 3 to 4 weeks. Patients return for frequent follow-up visits for the first 2 to 4 months after transplantation. The patient's referring physician is asked to send results of any laboratory testing to the NIH researchers at least every 3 months for the first 3 years and annually thereafter. Patient follow-up visits are scheduled at NIH at 1, 2, and 3 years after transplantation. After 3 years, participants are offered the opportunity to enroll in NHLBI's long-term evaluation and follow-up care protocol.

Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach (Kiadis Pharma). Older subjects will receive a lower dose of irradiation to reduce the regimen intensity.

To determine appropriate level of post transplant immunosuppression, we will utilize a three sequential de-escalation stage design involving 17 subjects per cohort (minimum 17, maximum 51 total evaluable subjects in study). Stopping rules for non-relapse mortality in each cohort will determine whether to continue to the next stage; to continue accumulating subjects at the same level; or to stop the protocol.

Cohort 1: Low dose cyclosporine until day 90 then dose tapered to stop within 2 weeks.

Cohort 2: If no severe GVHD is encountered in Cohort 1, the cyclosporine withdrawal will begin on day 45.

Cohort 3: If no severe GVHD is encountered in Cohort 2, cyclosporine will not be used in the post-transplant period.

Primary endpoints will be the incidence of acute grade III/IV GVHD at day 90. Secondary endpoints will be standard transplant outcome variables: toxicity, non relapse mortality and survival.

Evaluation of selective depletion of alloreactive T cells to prevent graft vs host disease

Stem Cell Transplantation for Patients With Cancers of the Blood

Selective Depletion of Alloreacting T Cells Using a Photodepletion Technique to Prevent GVHD After HLA-Matched Peripheral Blood Stem Cell Transplantation for Subjects With Hematologic Malignancies

Patients will receive a selectively photodepleted lymphocyte product which will be delivered together with the T cell depleted stem cell product on the day of transplantation. Subjects will receive a conditioning regimen of cyclophosphamide, fludarabine and total body irradiation followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34-selection and a lymphocyte product that has been selectively depleted using the photodepletion approach. Older subjects will receive a lower dose of irradiation to reduce the regimen intensity. To determine appropriate level of post transplant immunosuppression, a three sequential de-escalation stage design for timing of cyclosporine will be utilized. To determine if selective T cell depletion using the photodepletion procedure can substantially reduce the number of severe acute GVHD (grade III/IV) after transplantation followed by low-dose or no immunosuppression.

National Heart, Lung, and Blood Institute (NHLBI)

Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach. Older subjects will receive a lower dose of irradiation to reduce the regimen intensity. To determine appropriate level of post transplant immunosuppression, a three sequential de-escalation stage design for timing of cyclosporine will be utilized.

Selective T Cell Depletion Transplant Recipients

Sex: Female, Male

United States

Region of Enrollment

Age, Categorical

Minocher Battiwalla, MD

Subjects affected by Acute Grade III/ IV GVHD

Subjects unaffected by Acute Grade III/ IV GVHD

Subjects will receive a myeloablative conditioning regimen of cyclophosphamide, fludarabine and total body irradiation, followed by an infusion of a stem cell product prepared using the Miltenyi CliniMacs system for CD34 selection and a lymphocyte product that has been selectively depleted using the photodepletion approach (Kiadis Pharma). Older subjects will receive a lower dose of irradiation to reduce the regimen intensity.

To determine appropriate level of post transplant immunosuppression.

The study accrued 31 transplant recipents and 30 donors. Of the 31 transplant recipients, there were 24 evaluable recipients. Seven of the 24 recipients did not receive transplantation.

To Determine if Selective T Cell Depletion Using the Photodepletion Procedure Can Substantially Reduce the Rate of Severe Acute GVHD (Grade III/IV) After Matched Sibling Transplantation Followed by Low-dose or no Immunosuppression.

Overall Study

Amino Acids

Angiogenesis Inhibitors

Tyrosine Kinase Inhibitors

Tyrosine

Samir HENNI, MD

project is a pilot prospective, longitudinal, before-after, open label multicentric study.

Antiangiogenic drugs and tyrosine kinase inhibitor (TKI) represent a new therapeutic issue in the treatment of several neoplasic tumors (colon, kidney, breast, lung, skin) and hemopathy. Antiangiogenic drugs acts through neutralization of the activity (e.g. bevacizumab) or the inhibition of post-receptor tyrosine kinase pathways (e.g. sunatinib, sorafenib), leading to a reduction and inhibition of the tumoral tissular neovascularization. Due to the ubiquitous role of and the systemic administration of the antiangiogenic drugs, almost all of them are responsible for several side effects, many involving the cardiovascular system (e.g. arterial hypertension, cardiomyopathies, proteinuria, bleedings,...) and leading to a reduction of the doses or withdrawal of the treatment. To date, the mechanism and the impact of these cardiovascular effects is not well understood involving structural (i.e. capillary rarefaction) and functional vascular dysfunction (i.e. vasomotor dysfunction, stiffening).

Vascular Dysfunction and Antiangiogenic Therapy

Micro and Macro Vascular Dysfunction Induced by Antiangiogenic Therapy: Identification of New Vascular Biomarkers (DYVA-AAGG)

arterial stiffness, diameter and resistance will be performed using echotracking technologies.

University Hospital, Angers

Infections

Communicable Diseases

Virus Diseases

Adenoviridae Infections

MVST

PBMCs will be collected by apheresis prior to mobilization for Hematopoietic stem cells collection, donor apheresis will be used partially to prepare DLIs per PI specification and remaining will be further processed by elutriation.

Monocytes and Lymphocytes are cryopreserved for further manufacture of MVSTr.

MVSTr

Allogeneic hematopoetic stem cell transplantation (SCT) is frequently complicated by life threatening viral reactivation. Conventional antiviral therapy is suboptimal for cytomegalovirus (CMV), adenovirus (AdV) and Epstein-Barr virus (EBV) and nonexistent for BK virus (BKV). An alternative approach to prevent viral reactivation is to infuse virus-specific cytotoxic T cells (CTL) prepared from the donor early after SCT. Such multivirus-specific CTL cells (MVST) have been successfully used in a number of centers to prevent or treat CMV, Ad and EBV. Activity of BKV-reactive cells has not been studied. Multi virus-specific T cells (MVST) are donor lymphocytes that are highly enriched for viral antigens and expanded in vitro before infusion into the transplant recipient. Viral reactivation is a particular problem inT cell depleted SCT. Median time to CMV reactivation is estimated as 28 days post T-depleted transplant, but infusion of MVST within the immediate post-SCT period has not been previously studied. This protocol will be the first of a planned series of cellular therapies to be layered on our existing T lymphocyte depleted transplant platform protocol 13-H-0144.

The aim of this study is to determine the safety and efficacy of very early infusion of MVST directed against the four most common viruses causing complications after T-depleted SCT. GMP-grade allogeneic MVST from the stem cell donor will be generated using monocyte-derived donor dendritic cells (DCs) pulsed with overlapping peptide libraries of immunodominant antigens from CMV, EBV, Ad, and BKV and expanded in IL-7 and IL-15 followed by IL-2 for 10-14 days. A fraction of the routine donor leukapheresis for lymphocytes obtained prior to stem cell mobilization will be used to generate the MVST cells. MVST passing release criteria will be cryopreserved ready for infusion post SCT.

Eligible subjects on NHLBI protocol 13-H-0144 will receive a single early infusion of MVST within 30 days (target day +14, range 0-30 days) post SCT. Phase I safety monitoring will continue for 6 weeks. Viral reactivation (CMV, EBV, Ad, BK) will be monitored by PCR by serial blood sampling. The only antiviral prophylaxis given will be acyclovir to prevent herpes simplex and varicella zoster reactivation. Subjects with rising PCR exceeding threshold for treatment, or those with clinically overt viral disease will receive conventional antiviral treatment. Patients developing acute GVHD will receive standard treatment with systemic steroids. These patients are eligible for reinfusion of MVST when steroids are tapered.

The clinical trial is designed as a single institution, open label, non-randomized Phase I/II trial of MVST in transplant recipients, designed as 3-cohort dose escalation Phase I followed by a 20 subject extension Phase II at the maximum tolerated dose of cells. Safety will be monitored continuously for a period of 6 weeks post T cell transfer. The primary safety endpoint will be the occurrence of dose limiting toxicity, defined as the occurrence of Grade IV GVHD or any other SAE that is deemed to be at least probably or definitely related to the investigational product. The primary efficacy endpoint for the phase II will be the proportion of CMV reactivation requiring treatment at day 100 post transplant. Secondary endpoints are technical feasibility of MSVT manufacture, patterns of virus reactivation by PCR, and clinical disease from EBV, Ad, BK, day 100 non-relapse mortality.

Allogeneic hematopoetic stem cell transplantation (SCT) is frequently complicated by life threatening viral reactivation. Conventional antiviral therapy is suboptimal for cytomegalovirus (CMV), adenovirus (AdV) and Epstein-Barr virus (EBV) and nonexistent for BK virus (BKV). An alternative approach to prevent viral reactivation is to infuse virus-specific cytotoxic T cells (CTL) prepared from the donor early after SCT. Such multivirus-specific CTL cells (MVST) have been successfully used in a number of centers to prevent or treat CMV, Ad and EBV. Activity of BKV-reactive cells has not been studied. Multi virus-specific T cells (MVST) are donor lymphocytes that are highly enriched for viral antigens and expanded in vitro before infusion into the transplant recipient. Viral reactivation is a particular problem inT cell depleted SCT. Median time to CMV reactivation is estimated as 28 days post T-depleted transplant, but infusion of MVST within the immediate post-SCT period has not been previously studied. This protocol will be the first of a planned series of cellular therapies to be layered on our existing T lymphocyte depleted transplant platform protocol 13-H-0144.

The aim of this study is to determine the safety and efficacy of very early infusion of MVSTr cells directed against the four most common viruses causing complications after T-depleted SCT. GMP-grade allogeneic MVSTr from the stem cell donor will be generated using or peripheral blood mononuclear cells (PBMCs) pulsed with overlapping peptide libraries of immunodominant antigens from CMV, EBV, Ad, and BKV and expanded in IL-7 and IL-15 followed by IL-2 for 14 days. A fraction of the routine donor leukapheresis for lymphocytes obtained prior to stem cell mobilization will be used to generate the MVST cells. MVST passing release criteria will be cryopreserved ready for infusion post SCT.

Eligible subjects on NHLBI protocol 13-H-0144 will receive a single early infusion of MVSTr on day +7 post transplant range 0-14 days) post SCT. Phase I safety monitoring will continue for 6 weeks after infusion. Viral reactivation (CMV, EBV, Ad, BK) will be monitored by PCR by serial blood sampling. The only antiviral prophylaxis given will be acyclovir to prevent herpes simplex and varicella zoster reactivation. Subjects with rising PCR exceeding threshold for treatment, or those with clinically overt viral disease will receive conventional antiviral treatment. Patients developing acute GVHD will receive standard treatment with systemic steroids. These patients are eligible for reinfusion of MVST when steroids are tapered.

The clinical trial is designed as a single institution, open label, non-randomized Phase I trial of MVSTr in transplant recipients, designed as a single cohort Phase I study. Safety will be monitored continuously for a period of 6 weeks post MVSTr transfer. The primary safety endpoint will be the occurrence of dose limiting toxicity (DLT), defined as the occurrence of Grade IV GVHD, Grade III cytokine release syndrome (CRS), Grade III autoimmunity or any other SAE that is deemed to be at least probably or definitely related to the investigational product.

Phase I/II Trial of Early Infusion of Rapidly-generated Multivirus Specific T Cells (MVST) to Prevent Post Transplant Viral Infections

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study for PRO of CML in Real Word	NCT05092048	CML (Chronic My...	questionnaire	18 Years -	Nanfang Hospital, Southern Medical University
A Study for PRO of CML in Real Word	NCT05092048	CML (Chronic My...	questionnaire	18 Years -	Nanfang Hospital, Southern Medical University
Stem Cell Transplantation for Patients With Cancers of the Blood	NCT00467961	CML (Chronic My... CLL (Chronic Ly... AML (Acute Myel... Acute Lymphocyt... MDS (Myelodyspl...	Miltenyi system	18 Years - 75 Years	National Institutes of Health Clinical Center (CC)
Vascular Dysfunction and Antiangiogenic Therapy	NCT02161978	Solid Tumor Tumor Angiogene... Endothelial Dys... CML (Chronic My...		18 Years -	University Hospital, Angers
Phase I/II Trial of Early Infusion of Rapidly-generated Multivirus Specific T Cells (MVST) to Prevent Post Transplant Viral Infections	NCT02231853	Chronic Lymphoc... CML (Chronic My... MDS (Myelodyspl... Acute Lymphobla... AML (Acute Myel...	MVST MVSTr	18 Years - 75 Years	National Institutes of Health Clinical Center (CC)
Stem Cell Transplantation for Patients With Cancers of the Blood	NCT00467961	CML (Chronic My... CLL (Chronic Ly... AML (Acute Myel... Acute Lymphocyt... MDS (Myelodyspl...	Miltenyi system	18 Years - 75 Years	National Institutes of Health Clinical Center (CC)
A Study for PRO of CML in Real Word	NCT05092048	CML (Chronic My...	questionnaire	18 Years -	Nanfang Hospital, Southern Medical University

Spots Global Cancer Trial Database for cml (chronic myelogenous leukemia)