Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Rare Diseases

Hematologic Neoplasms

Graft vs Host Disease

Hematologic Diseases

Homologous Wasting Disease

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

After preferred conditioning regimen for the patient, cyclophosphamide 50 mg/kg/day will be administered at +3 and +4 post transplant day. At +6 post transplant day, 2-8x10\^8 cell/kg mesenchymal stem cells will be infused.

mesenchymal stem cells

After preferred conditioning regimen for the patient, cyclophosphamide 50 mg/kg/day will be administered at +3 and +4 post transplant day.

cyclophosphamide administration

Mesenchymal stem cells (MSCs) have been used in the treatment and prevention of graft-versus host disease (GVHD). In this study the investigators aim to present the efficacy of mesenchymal stem cells in graft versus host disease prophylaxis and effect of engraftment in haploidentical recipients. Forty patients aged older than 18 who have indications for haploidentical hematopoietic stem cell transplantation will be included to the study. MSCs will be isolated from donor bone marrows and infused to the patient after conditioning regimen on day +6. If the haploidentical transplantation results improve with MSCs treatment it would be possible to ameliorate the problem of HLA-matched donor paucity in Turkey and prefer haploidentical donors.

Mesenchymal stem cells (MSCs) have been utilized in the treatment and prevention of graft-versus-host disease(GVHD) after allogeneic hematopoietic stem cell transplantation (alloSCT). However, studies on MSC use in alloSCT from haploidentical donors (haploSCT) have been limited.

In this study, the investigators aim 1) to evaluate MSCs' efficacy in GVHD prophylaxis and effect on engraftment of the haploidentical graft, 2) to improve the success rate of haploSCT by further decreasing GVHD incidence and graft failure rate. With higher haploSCT success rates, haploidentical donors would be important alternative graft sources in patients without HLA-matched donors.

Forty patients who present to Ankara University, School of Medicine, Division of Hematology with hematological malignancies and have indications for haploSCT will be included in the study after informed consent is obtained. MSCs will be procured and isolated from donor bone marrows. MSCs will be isolated, cultured, and stored in the good manufacturing practice (GMP) laboratory in Ankara University Stem Cell Institute. Donor bone marrow will be harvested, four to six weeks prior to transplantation, for MSC isolation and culture. Patients will receive either an ablative or non-ablative induction regimen based on their age, diagnosis, and the disease status at the time of transplantation. Donor bone marrow will be harvested a second time on the day of transplantation and the procured bone marrow graft will be infused to the patient the same day. GVHD prophylaxis will include post-transplantation cyclophosphamide (Cy) on days +3 and +4 (50 mg/kg/day), tacrolimus, and mycophenolate mofetil. Stored MSCs will be infused to the patient on day +6. The endpoints include graft failure rate, GVHD incidence, transplant-related mortality, disease-free survival, and overall survival.

The investigators aim to evaluate the utility of MSCs in improving haploSCT results and to enhance the reliability and success of haploSCT. Successful transplants from haploidentical donors would ameliorate the problem of matched donor paucity in countries with a limited number of hematopoietic stem cell donors, such as Turkey, and would establish haploidentical donors an alternative donor source for patients without matched donors in Turkey. As haploidentical donors may be parents or children, rapid and easy access to donors would decrease wait times for alloSCT. Moreover, national current account deficit may be reduced through using grafts obtained from haploidentical donors residing in Turkey instead of grafts from foreign stem cell/umbilical cord banks.

In this project, the investigators seek to develop clinical therapy applications in concordant with the ambition of "renewal and repair of human cells, tissues, and organs through cellular therapy and cellular products" that is included in the The Scientific and Technological Research Council of Turkey 1003 Call for Projects.

Mesenchymal Stem Cell Infusion in Haploidentical Hematopoietic Stem Cell Transplantation in Patients With Hematological Malignancies

The Scientific and Technological Research Council of Turkey

Ankara University

MD, Department of Hematology, Clinical Professor

Symptoms and General Pathology

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Diseases and Abnormalities at or Before Birth

Occupational Diseases

Wounds and Injuries

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Syndrome

COVID-19

Communicable Diseases

Respiratory Distress Syndrome

Respiratory Distress Syndrome, Newborn

Acute Lung Injury

Laboratory Infection

Lung Injury

Disease Attributes

Pneumonia

Pneumonia, Viral

Respiratory Tract Infections

Virus Diseases

Coronavirus Infections

Coronaviridae Infections

Nidovirales Infections

RNA Virus Infections

Lung Diseases

Respiratory Tract Diseases

Respiration Disorders

Premature Birth

Infant, Premature, Diseases

Infant, Newborn, Diseases

Respiratory Distress Syndrome, Infant

Acute Respiratory Distress Syndrome

Acute Graft Versus Host Disease

Patients receive MSCs as in the Pilot study.

Patients receive MSCs IV over 1-2 hours on day 1. Patients may receive a second infusion of MSCs within 7 days after the first infusion per physician discretion.

Best Practice

Mesenchymal Stem Cell

Bethany Overman

Bethany J. Overman

Amanda Olson

This is a phase I trial followed by a phase II randomized trial. The purpose of phase I study is the feasibility of treating patients with acute respiratory distress syndrome (ARDS) related to COVID-19 infection (COVID-19) with cord blood-derived mesenchymal stem cells (MSC). The purpose of the phase II trial is to compare the effect of MSC with standard of care in these patients. MSCs are a type of stem cells that can be taken from umbilical cord blood and grown into many different cell types that can be used to treat cancer and other diseases. The MSCs being used for infusion in this trial are collected from healthy, unrelated donors and are stored and grown in a laboratory. Giving MSC infusions may help control the symptoms of COVID-19 related ARDS.

PRIMARY OBJECTIVE:

I. To assess the safety of administering cord blood derived mesenchymal stem cell (CB-MSC) infusions for treatment of COVID-19 acute respiratory distress syndrome (ARDS).

SECONDARY OBJECTIVES:

I. In the group of patients who present intubated on ventilator support, assess the proportion that are able to be successfully extubated.

II. In the group of patients who present requiring supplemental oxygen but otherwise breathing without assistance, assess the rate of progression to intubation.

III. Estimate the survival rate at day 30 post treatment separately by group.

IV. Determine the treatment effect on clinical parameters, oxygenation and respiratory parameters:

IVa. Resolution of fever. IVb. Changes in oxygen demand (increased oxygen saturation at similar fraction of inspired oxygen \[FiO2\] or decreased FiO2 requirement).

IVc. Progression to mechanical ventilation. IVd. Length of mechanical ventilation. IVe. Decrease in positive end-expiratory pressure (PEEP) in intubated patients. IVf. Decrease in FiO2 in intubated patients.

V. Determine the treatment effect on laboratory markers:

Va. Complete blood count. Vb. C-reactive protein (CRP). Vc. Ferritin. Vd. D dimer. Ve. Procalcitonin. Vf. Cytokine levels. VI. Estimate hospitalization and intensive care unit (ICU) stay. VII. Report on study related adverse events.

OUTLINE:

Currently not shipping cells outside of MD Anderson Cancer Center in Houston.

PILOT STUDY: Patients receive MSCs intravenously (IV) over 1-2 hours on day 1. Patients may receive a second infusion of MSCs within 7 days after the first infusion per physician discretion.

PHASE II STUDY: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive MSCs IV over 1-2 hours on day 1. Patients may receive a second infusion of MSCs within 7 days after the first infusion per physician discretion.

ARM II: Patients receive standard of care.

After completion of study treatment, patients are followed up at days 7, 14, 30, 60, and months 6 and 12.

Cord Blood-Derived Mesenchymal Stem Cells for the Treatment of COVID-19 Related Acute Respiratory Distress Syndrome

Study of Cord Blood Derived Mesenchymal Stem Cells for Treatment Acute Respiratory Distress Syndrome

Serious adverse events with be comprised of grade 3 or 4 graft versus host disease or death and will be estimated and reported overall and by group, along with 95% confidence intervals.

Will be estimated and reported with 95% confidence intervals.

The effect of MSCs on clinical parameters will be assessed. Continuous clinical parameters will be summarized by means, medians, standard deviations, ranges, and quartiles. Categorical parameters will be summarized by frequency tables.

The effect of MSCs on oxygenation parameters will be assessed. Continuous oxygenation parameters will be summarized by means, medians, standard deviations, ranges, and quartiles. Categorical parameters will be summarized by frequency tables.

The effect of MSCs on respiratory parameters will be assessed. Continuous respiratory parameters will be summarized by means, medians, standard deviations, ranges, and quartiles. Categorical parameters will be summarized by frequency tables.

The effect of MSCs on laboratory markers will be assessed. Continuous laboratory parameters will be summarized by means, medians, standard deviations, ranges, and quartiles. Categorical parameters will be summarized by frequency tables.

All grades of infusion-related adverse events will be summarized by grade and type.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Mouth and Tooth Diseases

Head and Neck Neoplasms

Xerostomia

Salivary Gland Diseases

Mouth Diseases

Stomatognathic Diseases

Central Nervous System Depressants

Analgesics

Anesthetics

The surgical procedure is done under local anaesthesia using ultrasonic guidance and sterile technique. After receiving the MSC-suspension , the surgeon will identify the submandibular glands and inject the suspension MSCs into the submandibular gland. Calculation of injected number of MSCs pr. participant rests on the following calculation: 2.8 x 10\^6 MSC / Cm\^3 X volume , where volume is the volume of the submandibular gland, and a gland-volume of app. 7-8cm3 is the norm. Therefore the amount of cells given to each participant will be app. 4.6 x 10\^7 MSC in total. Afterwards the participant will be given a band-aid and over the counter analgesics.

The surgical procedure is done under local anaesthesia using ultrasonic guidance and sterile technique. After receiving the placebo-suspension , the surgeon will identify the submandibular glands and inject the suspension. Placebo will be 2ml of Isotonic NaCl (0,9mg/ml) and HA 1%.

Mesenchymal stem cell

Isotonic NaCl

The current study aims to assess the safety and feasibility of the injection of autologous adipost tissue derived MSCs on radiation-induced salivary gland hypofunction and xerostomia in head and neck cancer participants. The project can potentially help to develop a clinically relevant treatment option for the growing number of patients suffering from xerostomia after radiotherapy. The development of new therapies is especially important, since only sub-optimal symptomatic treatments are currently available and the symptom of xerostomia greatly reduces the quality of life.

Design Randomized, controlled trial with blinding. To maintain allocation concealment all participants, care givers, trial investigators and outcome assessors except the Blood Bank staff will be blinded to the intervention. Staff from the Blood Bank will not have direct contact with the patients (hereafter the participants) as such.

Project plan For inclusion in the study participants will have their usual medical history taken according to guidelines from the Ear, Nose and Throat Surgical Department, Copenhagen University Hospital Rigshospitalet.

All participants will undergo a mini lip-suction, from which MSCs will be ex vivo expanded in a good manufacturing practice (GMP)-approved clean room facility (The Blood Bank, section 2014). When the cells arrive at the Blood Bank, participants will be randomized to either ex vivo expansion of their mesenchymal stem cells or having them frozen for potential later use. Expected ex vivo expansion phase is 3-4 weeks. The purification and isolation will be based on a protocol previously approved for clinical use.

Amount of MSCs required for injection Based on published animal studies the amount given for xerostomia to mice varies from 2 x 105 to 2 x 106 \[19\]. To convert these mice data to a realistic dose in humans we have extrapolated based on the following data: The volume density of submandibular glands very closely approximates 1 (1.06-1.07 mg/mm3) \[27\]. In the mice studies on radiotherapy the mean gland weight was approximately 350mg, which corresponds to an approximate volume of 350mm3. Therefore the mouse dose pr. gland volume is approximately 286.000-2.860.000cells pr. cm3 gland (when calculated from either 1 x 105 to 1 x 106). The volume of the submandibular gland in human subjects after radiotherapy is 6.6-7.9cm3 \[28\]. This corresponds to an approximate dose pr. patient of between 1.9 x 106 to 2.2 x 106, or 1.9 x 107 to 2.2 x 107 cells pr. submandibular gland. From the above assumptions and in order not to give to few cells we have chosen to proceed with the maximum dose corresponding to 2.8\*10\^6 MSC/cm\^3 gland, i.e. a maximum total dose per patient of approximately 4,6 \* 10\^7 MSCs. However to standardize the dose given to patients, the amount given will be standardized to the size of their submandibular glands, as described below.

Injection of MSCs into submandibular glands Subjects will go to the ENT-department, section 2073 for inpatient procedures. The surgical procedure is done under local anaesthesia using ultrasonic guidance and sterile technique. After receiving the MSC-suspension or placebo-suspension, the surgeon will identify the submandibular glands and inject the suspension MSCs. Calculation of injected number of MSCs pr. participant rests on the following calculation: , where volume is the volume of the submandibular gland, and a gland-volume of app. 7-8cm3 is the norm. Therefore the amount of cells given to each participant will be app. in total. Afterwards the participant will be given a band-aid and over the counter analgesics. The MSCs will be suspended in Isotonic NaCl (0,9 mg/ml) and Human Albumin (HA) 1% to a final volume of 2ml. Placebo will be 2ml of Isotonic NaCl (0,9mg/ml) and HA 1%.

Follow-up MRI of the recipient place will be performed after 3-4 weeks and 3-4 months postoperatively. MRI is used for volume determination of salivary glands and control of recipient place.

After 3-4 months, a small biopsy is randomly taken from one of the two salivary glands. The procedure takes place under local anaesthesia. Histology is determined (samples are blinded to the pathologist).

When the final MRI, biopsy and salivary function test has been performed approx. 3-4 months after treatment specific study related tests and activities are concluded. To detect late complications or late adverse events all study participants who received MSC-treatment are invited for a check-up 1 year and 3 years after treatment.

Safety, isolation and propagation of MSC The Blood Bank has its cell-tissue approval from the Danish Health and Medicines Authority (according to the Danish Tissue Law), as well as a Manufacturer's/Importer's Authorisation regarding Human Medicinal Products, the necessary physical facilities, personnel and operational resources to produce MSCs in accordance with good manufacturing practice (GMP).

The MSC product will be tested for recognized surface markers (CD73, CD90, CD105,) using flow cytometry, and undergo general quality checks before the final release (cell viability and tests for microorganisms). With regard to the cultivation of the MSC we will use basal medium supplemented with human platelet lysate from healthy blood donors instead of the former use of animal-derived serum (fetal bovine serum, FBS). This has the following benefits: 1) No likelihood of transfection of both known and unknown animal pathogens, or risk of xeno-immunization 2) Small batch-to-batch variation and thus more consistent growth performance, since each group is prepared from approx. 50 healthy donors.

All harvest, isolation, expansion, etc. of MSC will be in accordance with GMP regulations. The Blood Bank has clean room facilities approved by the Danish Health and Medicines Authority for GMP compliant cell expansion for clinical use, and all studies will be carried out by specially trained personnel.

Assessment of xerostomia and subjective treatment outcome The subjective effect of the treatment is assessed by a 100 mm visual analogue scale of xerostomia filled out by the patient \[31\] and a physician-rated questionnaire \[32\], both carried out before as well as after treatment. Each participant will also be asked about daily symptoms of dry mouth according to the UKU side-effect rating scale item 3.3 \[29\]. This scale includes four scores where 0 denotes no feeling of dry mouth, 1 denotes a slight feeling of dry mouth, 2 denotes a severe feeling of dry mouth, and 3 denotes troublesome feeling of dry mouth that makes speech and eating difficult.

Assessment of salivary flow rate and objective treatment outcome Changes in the secretion rate of the unstimulated whole saliva in the oral cavity is probably the most important parameter for the biological development of xerostomia and accompanying pathological oral conditions. Whole saliva, e.g., the mixed secretions from the major and minor salivary glands is mixed in the oral cavity. A correct determination of this value is crucial for the assessment of treatment outcome in this project. For assessment of the saliva flow rate, whole saliva will be collected between 9 and 12 a.m. Subjects will refrained from eating, drinking, smoking and oral hygiene for 2 hr before the collection. After being seated upright in a chair, they relax for 5 min and are then instructed to make as few movements as possible, including swallowing, during the collection.

Before and after treatment unstimulated whole saliva will be collected using the spitting method \[33\] where participants spit their saliva into a collection container over a period of 15 minutes. The salivary flow rate (SFR) (ml / min) is determined as the increase in weight of the container divided by the collection time in minutes.

After the collection of unstimulated saliva, the subjects are instructed to chew on 1 g of sterile paraffin wax. They will be asked to keep their mouths closed during chewing and to avoid swallowing. Every 60 sec they will be asked to spit into a new saliva collector before starting a new chewing period. This will be repeated for 5 min.

To assess treatment outcome of the submandibular glands, saliva is also collected directly from the floor of the mouth in an unstimulated and stimulated state. The unstimulated whole saliva flow rate of the submandibular glands will be assessed by the swab method with cotton rolls placed buccally in each maxillary molar region and under the tongue on the floor of the mouth. Immediately prior to the start of collection they will be asked to swallow, in case this is not possible saliva will be extracted by a pipette. Collection takes place during two subsequent periods of 3 min and, at the end of each period, the chin and lips will be wiped with a napkin. Saliva flow rates are determined by weight (1 g equals 1 ml of saliva) with rolls and napkins weighed before collection and reweighed after. The flow rates is calculated as the increment in weight during collection and expressed as millilitres per minute. Saliva from the cotton rolls will be extracted by centrifugation (1500g) and analyzed for its composition. This stimulated collection process will be performed afterwards with citrus-containing rolls to stimulate the submandibular glands maximally. From each of these collections of saliva, saliva will be aliquoted and stored at -800C.

Chemical analysis of saliva Whole saliva contains a large number of bacteria and epithelial cells, as well as gingival crevicular fluid. Therefore, whole saliva is normally not suited for the analysis of sensitive chemical parameters. For this purpose, the selectively collected saliva from individual glands is much better. As a result, the majority of analyzes can be performed from either the parotid and submandibular gland / sublingualis saliva. The following analyzes will be performed on the collected saliva: pH and bicarbonate by ionic balance estimation \[34\], sodium, potassium, calcium, phosphate, chloride and fluoride \[35\], total protein and selected proteins \[36\] and amylase \[37\]. The purpose of the studies is to evaluate whether saliva will be normalized after treatment, and thus provide an estimate of the saliva dental and mucosal protective capacity before and after treatment.

Data collection and analysis Source data: There will be source documentation for all data in Case Report Form (CRF).

The study director allows direct access to study data and study documents for the monitoring, audit and inspection of the Science Ethics Committee, the Danish Health and Medicines Authority or similar authorities in other countries. Permission will be sought from the DPA for the processing of personal data under the Danish Data Protection Act. Applications will be sent via the legal secretariat, Rigshospitalet.

Mesenchymal Stemcells for Radiation Induced Xerostomia

Mesenchymal Stem Cells for Radiation-induced Xerostomia (MESRIX) in Previous HPV-positive Oropharyngeal Head and Neck Cancer Patients - A Safety and Feasibility Study

Criteria for Adverse Events (CTCAE). Since this is a local treatment with MSCs the primary safety measures are: All measures of adverse events will be graded according to Common Terminology

Rigshospitalet, Denmark

MD, PhD student

The surgical procedure is done under local anaesthesia using ultrasonic guidance and sterile technique. After receiving the MSC-suspension , the surgeon will identify the submandibular glands and inject the suspension MSCs into the submandibular gland. Calculation of injected number of MSCs pr. participant rests on the following calculation: 2.8 x 10\^6 MSC / Cm\^3 X volume , where volume is the volume of the submandibular gland, and a gland-volume of app. 7-8cm3 is the norm. Therefore the amount of cells given to each participant will be app. 4.6 x 10\^7 MSC in total. Afterwards the participant will be given a band-aid and over the counter analgesics.

Mesenchymal stem cell: Stemcells injected into submandibularis

Stemcells Injected Into Submandibularis

The surgical procedure is done under local anaesthesia using ultrasonic guidance and sterile technique. After receiving the placebo-suspension , the surgeon will identify the submandibular glands and inject the suspension. Placebo will be 2ml of Isotonic NaCl (0,9mg/ml) and HA 1%.

Isotonic NaCl

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Mesenchymal Stem Cell Infusion in Haploidentical Hematopoietic Stem Cell Transplantation in Patients With Hematological Malignancies	NCT03106662	Hematopoietic S...	mesenchymal ste... cyclophosphamid...	18 Years -	Ankara University
Cord Blood-Derived Mesenchymal Stem Cells for the Treatment of COVID-19 Related Acute Respiratory Distress Syndrome	NCT04565665	COVID-19 Infect... COVID-19-Associ... Hematopoietic a... Malignant Solid... Symptomatic COV...	Best Practice Mesenchymal Ste...	18 Years -	M.D. Anderson Cancer Center
Mesenchymal Stemcells for Radiation Induced Xerostomia	NCT02513238	Xerostomia	Mesenchymal ste... Isotonic NaCl	18 Years -	Rigshospitalet, Denmark
Mesenchymal Stemcells for Radiation Induced Xerostomia	NCT02513238	Xerostomia	Mesenchymal ste... Isotonic NaCl	18 Years -	Rigshospitalet, Denmark

Spots Global Cancer Trial Database for mesenchymal stem cell