Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Leukemia

Mastocytosis

Graft vs Host Disease

Mastocytosis, Systemic

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Mast Cell Activation Disorders

Homologous Wasting Disease

Systemic Mastocytosis

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Stem cell transplantation

This study will investigate the safety and effectiveness of an experimental stem cell transplant procedure for treating mastocytosis-a disease of abnormal mast cell growth. Patients often feel faint, have skin problems, joint and bone pain, low blood counts and enlarged liver, spleen or lymph nodes. As yet, there is no cure for mastocytosis, and treatment is aimed at controlling symptoms.

Stem cells are cells produced by the bone marrow that mature into the different blood components-white cells, red cells and platelets. Transplantation of allogeneic (donated) stem cells is a mainstay of therapy for some forms of leukemia. Patients first receive intensive chemotherapy and radiation to rid the body of cancer cells. This "conditioning" is followed by transplantation of donated stem cells to generate new, healthy bone marrow. In addition to producing the new bone marrow, the donated cells also fight any residual tumor cells that might have remained in the body. This is called a "graft-versus-tumor" effect. This study will examine whether a stem cell transplant from a healthy donor can similarly target and destroy mast cells in a "graft-versus-mast cell" effect. Also, to try to reduce the harmful side effects of chemotherapy and radiation, this study will use lower dose chemotherapy and no radiation.

Patients with advanced mastocytosis between 10 and 80 years old may be eligible for this study. They will be

tested for HLA type matching with a sibling and will undergo a medical history, physical examination and several tests to determine eligibility for the study.

Participants will undergo apheresis to collect lymphocytes (a type of white blood cell) for immune function tests. In this procedure, blood is drawn through a needle in the arm, similar to donating a unit of blood. The lymphocytes are then separated and collected by a cell separator machine, and the rest of the blood is returned through a needle in the other arm. Patients will also have a central venous line (flexible plastic tube) placed in their upper chest leading to a vein. This line will remain in place throughout the transplant and recovery period and will be used to transfuse blood components, administer medicines, infuse the donated stem cells, and draw blood for tests. Patients will begin conditioning with cyclophosphamide, starting 7 days before the transplant, and fludarabine, starting 5 days before the transplant, to prevent rejection of the donated cells. From 1 to 3 days after the chemotherapy is completed, the stem cells will be transfused through the central venous line. Also, from 4 days before the transplantation until about 3 months after the procedure, patients will receive cyclosporine and mycophenolate mofetil-drugs that help prevent both rejection of the donated cells and attack by the donor cells on the patient's cells (called graft-versus-host disease).

Patients will stay in the hospital about 20 to 30 days after the transplant. After discharge, they will continue to take antibiotics, cyclosporine and mycophenolate mofetil at home. If the mastocytosis progresses, cyclosporine and mycophenolate mofetil will be tapered over 4 weeks. If the mastocytosis persists, patients may receive additional transfusions of donor lymphocytes to help kill the mast cells.

Patients' progress will be followed weekly or twice weekly for 3 months, then at 6, 12, 18, 24, 30, 36, 48 and 60 months after transplant, and then twice a year for various tests, treatments and examinations.

Mastocytosis is a disease characterized by excessive numbers of mast cells in skin, bone marrow and internal organs such as liver, spleen and lymph nodes. Its genesis appears to be related to somatic mutations in c-kit, the receptor for mast cell growth factor. Although most patients present with the indolent form of the disease, approximately one-third of the patients have an associated hematologic disorder such as a myeloproliferative state or myelodysplastic syndrome. Patients with advanced forms of the disease, including those with an associated hematologic disorder have a poorer prognosis than those with indolent disease. There is no treatment known to cure or improve the natural course of mastocytosis. Since mast cells arise in the bone marrow from a CD34+ progenitor, bone marrow transplantation may offer the only hope for a cure.

In this protocol, we propose to treat patients with advanced forms of mastocytosis with an allogeneic stem cell transplant from an HLA-identical sibling, using a low intensity non-myeloablative regimen. This approach has the advantage of decreasing the transplant-related toxicity while allowing adequate immunosuppression to establish stem cell and lymphocyte engraftment. Donor derived CD4 and CD8 lymphocytes, which are important in killing of leukemic cells by mounting a "graft versus leukemia" effect, should be useful in the elimination of aberrant mast cells and their progenitors, that is "graft-versus-mast cell effect". This mechanism may be particularly relevant in mastocytosis as point mutations of c-kit may constitute an antigenically distinct T-cell target for recognition by the engrafted donor cells.

The primary end point of this study is regression of mastocytosis. The secondary end points are engraftment, hematologic response, degree of donor-host chimerism, incidence and severity of acute and chronic GVHD, transplant related morbidity and mortality, relapse, disease free survival, and overall survival.

Stem Cell Transplantation to Treat Systemic Mastocytosis

Low Intensity Preparative Regimen Followed by HLA-Matched, Mobilized Peripheral Blood Stem Cell Transplantation for Systemic Mastocytosis

National Heart, Lung, and Blood Institute (NHLBI)

Diseases and Abnormalities at or Before Birth

Symptoms and General Pathology

Dermatitis, Atopic

Dermatitis

Eczema

Blister

Skin Diseases

Skin Diseases, Genetic

Genetic Diseases, Inborn

Skin Diseases, Eczematous

Hypersensitivity

Hypersensitivity, Immediate

Cytokine Production Patterns in Patients with Systemic Mastocytosis Compared with Atopic Dermatitis and Healthy Individuals

Summary: This study will examine how mast cells (cells involved in allergic reactions) migrate and multiply in the skin of patients with mastocytosis, a condition characterized by too many mast cells in the body. The mast cells tend to multiply in the skin, causing dark, itchy skin spots known as urticaria pigmentosa. This study will determine if the skin of patients with mastocytosis produces chemicals called cytokines that cause mast cells to migrate to the skin and multiply. The findings will be compared with those from normal volunteers and patients with atopic dermatitis, a skin disease characterized by recurrent itchy rash usually seen in people with a family history of allergies.

Healthy volunteers, patients with mastocytosis and patients with atopic dermatitis 18 years of age and older may be eligible for this study. Participants will have the following tests and procedures:

* Suction blisters - Two to eight small blisters will be raised on the forearm using gentle suction. The fluid in the blisters will be collected with a syringe to study the chemicals produced by the skin. The tops of the blisters may be removed for research.
* Template study - Patients with high cytokine content in the blister fluid may have a template study. For this procedure, a plastic block (template) with holes matching the blister sites is placed over the blistered area. The wells of the template are filled with salt water and the fluid is removed with a syringe at 3, 8 and/or 24 hours. Patients are hospitalized for 24 hours for this study.
* Skin biopsy - A skin biopsy will be done to correlate cytokine levels with the number of mast cells in the skin. An area of skin is numbed with an anesthetic and a small circular area about the size of a pencil eraser is removed, using a sharp cookie cutter-type instrument.
* Blood draw - About 4 tablespoons of blood will be drawn to compare the chemicals in the blood with those in the blister fluid. The blood will also be analyzed for a complete blood count, clotting factors and substances that may be elevated in people with allergies.

Systemic mastocytosis is a disease characterized by an abnormal accumulation of mast cells in skin, bone marrow and viscera. Precise mechanisms of events leading to the migration and proliferation of mast cells in skin is not known. We propose to investigate the in vivo cytokine and chemokine production patterns of human skin in patients with mastocytosis and compare these findings to those of patients with atopic dermatitis and to healthy volunteers, using the suction blister technique. The cytokines/chemokines of interest in this study are stem cell factor (SCF), interleukin (IL)-3, IL-4, IL-6, IL-9, IL-10, TNF-alpha, TGF-beta, MCP-1 and RANTES, all of which have been shown to take part in the proliferation, differentiation or chemotaxis of mast cells. Our hypothesis is that human skin is producing mediators which allow the mast cells to migrate and proliferate in skin, resulting in the clinical picture of urticaria pigmentosa. Suction blisters will be generated in patients, and the cytokine/chemokine contents of the blister fluids will be analyzed by immunoassay. If the chemokine content of the blister fluid is found to be high, chemotaxis of mast cell precursors to the skin may also be examined in vivo by placing a template filled with sterile saline over the blister sites. Punch biopsies will be performed to correlate cytokine levels with mast cell numbers. This study will aid in understanding the pathogenesis of cutaneous mast cell disease and may provide insights into the regulation of mast cell growth and differentiation in tissue-specific microenvironments. It is hoped that these studies will contribute to the design of novel treatment strategies against mast cell associated skin diseases.

Cytokine Production Patterns in Patients With Systemic Mastocytosis Compared With Atopic Dermatitis and Healthy Individuals

Determination of Cytokine Production Patterns in the Skin of Patients With Systemic Mastocytosis and Atopic Dermatitis Using the Suction Blister Technique

National Institute of Allergy and Infectious Diseases (NIAID)

Patients have mast cell hyperplasia compatible with a diagnosis of systemic mastocytosis (applicable to systemic mastocytosis patients only) or other allergic, hematologic, orimmunologic condition.

Melody C Carter, M.D.

This study will investigate mast cell precursors that circulate in the blood. In a group of diseases collectively known as mastocytosis, mast cells accumulate in abnormal amounts in the skin, lymphoid tissues, bone marrow, liver and spleen. Some forms of mastocytosis have a generally good prognosis; for others, the prognosis is poorer. There is no known cure for any form of the disease. A better understanding of mast cells and how they respond to certain substances may provide insights that will lead to effective treatments for mastocytosis.

Patients with systemic mastocytosis and normal healthy volunteers between the ages of 20 and 60 may be eligible for this 8-day study. Participants will undergo the following procedures:

* Day 1 Medical history, physical examination, and blood tests to assess general health status
* Days 2 through 6 Daily injections under the skin of G-CSF a hormone that stimulates white blood cell production
* Day 7 Leukapheresis a procedure for collecting large numbers of white blood cells. In leukapheresis, blood is drawn through a needle placed in an arm and channeled into a cell separator machine. The white cells are collected and the rest of the blood is returned to the body through a needle in the other arm. The procedure takes up to 3 hours.
* Days 7 and 8 Blood draw (about 1 teaspoon) to monitor white blood cell counts.

The purpose of this protocol is to obtain large numbers of CD34+ cells from the peripheral blood of healthy volunteers and patients with systemic mastocytosis or other related allergic, hematological, and immunological conditions by leukapheresis for culture and characterization of mast cell progenitor cells and their response to various cytokines and anti-mitotic agents. Healthy volunteers and patients will be adults of both sexes from 18 to 70 years of age. Granulocyte colony stimulating factor (G-CSF) will be administered to healthy volunteers at dose of 10 mcg/kg/day as a subcutaneous dose daily for 5 days not to exceed 960mcg. Patients will receive Plerixafor at a dose of 0.24 mg/kg as a single subcutaneous dose not to exceed 24mg the night before leukapheresis as a mobilizing agent for CD34+ cells. In identified patients where leukapheresis yield is considered adequate without stimulation by the principal investigator, leukapheresis may proceed without stimulation. Healthy volunteers will undergo a single leukapheresis at day 7, and patients will undergo a single leukapheresis at day 3 or 4. This is not a therapeutic protocol and does not involve reinfusion of any manipulated cells, viruses or DNA constructs back into human subjects.

Study of Mast Cell Precursors

The Characterization of CD34+ Derived Mast Cell Precursors

Use of G-CSF administration healthy volunteers to mobilize and enhance CD34+ hematopoietic progenitor cell numbers into the peripheral blood in order to culture and characterize human mast cells, study and characterize CD34+ -derived human mast cells.

Collection of CD34+ cells with or without use of Plerixafor administration in patients with systemic mastocytosis and other related allergic, hematological and immunological conditions to mobilize and enhance CD34+ cells into the peripheral blood to culture and learn how mast cells contribute to these disease states.

Urticaria

Urticaria Pigmentosa

This study will evaluate children with mastocytosis, a disease of excessive mast cells in tissues such as skin and bone marrow, to identify the cause of the disease and describe its course. Mast cells can release chemicals that cause itching, blisters, flushing, bone pain, and abdominal pain. Usually, mastocytosis in children involves the skin only and is of limited duration. This study, however, will focus on children with more severe disease that more closely resembles adult-onset mastocytosis.

Patients up to 21 years of age with childhood-onset mastocytosis may be eligible for this study. Candidates must have one or more of the following abnormalities, which indicate severe disease: enlarged liver or spleen; diffuse skin involvement; history of gastrointestinal bleeding or peptic ulcer; bone marrow biopsy with abnormal mast cells either in number or shape; elevated blood levels of the enzyme tryptase; or abnormal hemoglobin, white blood cells, platelets, or clotting factors.

Participants will have a medical history and physical examination; various blood tests, including studies to identify genetic changes that are important in the growth, development, and functioning of human mast cells; and bone marrow aspiration and biopsy. For the bone marrow procedure, the skin over the hipbone and the outer surface of the bone itself are numbed with an injection of local anesthesia. Then, a special needle is inserted into the hipbone and about 2 tablespoons of bone marrow are drawn into a syringe. Another needle is then inserted through the first needle to collect a small piece of the bone marrow. Pain will be managed according to the individual patient s needs. Additional procedures, such as a gastroenterology consultation, colonoscopy to examine the colon, or computerized axial tomography (CT) or ultrasound of the abdomen to assess the liver and spleen, may be done if medically indicated. Standard medical treatment, including antihistamines for itching or steroids for abdominal cramping or diarrhea, will be recommended as appropriate.

Patients biologic parents may also be enrolled to provide a blood sample for genetic analysis and a bone marrow aspirate and biopsy for clinical and research purposes.

Patients will return to NIH once a year for follow-up evaluations until their disease is stable or until the 5-year study ends.

...

Mastocytosis in infants and children is an unusual disease characterized by an excess of mast cells in tissues. In pediatric onset mastocytosis, disease is usually localized to the skin and disease is considered to be of limited duration. However, a subset of children appear to develop a clinical picture resembling that observed in adults who have adult-onset disease. This study will focus on children with more severe mastocytosis in an attempt to define its pathogenesis, focusing on mutations and polymorphisms in genes regulating mast cell proliferation and survival to determine if they might contribute to this disease pattern. If severe pediatric-onset disease does not fit within the existing classification, new criteria of diagnosis must be proposed for the pediatric age group.

This study will examine children and young adults age birth to 21 years with pediatric-onset disease previously enrolled on NIAID mastocytosis protocols, or as a result of physician referral, which have disease more consistent with adult-onset disease or parameters associated with increased morbidity. The evaluation may include serum tryptase, blood count, bone marrow biopsy and aspirate, morphology and mutational analysis. Subjects may be asked to return in 12-24 months for assessment. If relevant mutation effecting mast cell growth and function are identified, such mutations will be sought in the biologic parents as appropriate, but only when such mutations are believed to be germ line (not somatic) mutations. This study will aid in the understanding of the characteristics of severe mastocytosis in the pediatric age group.

Cause and Natural Course of Pediatric-Onset Mastocytosis

Determining the Pathogenesis of Systemic Pediatric-Onset Mastocytosis

A blood test tube (only for scRNAseq, 2 tubes of 10 ml per patient)

scRNAseq

two Skin biopsies

one Skin biopsies

Cristina Bulai Livideanu, MD

This study will aim to study the heterogeneity of skin-resident mast cells and of blood circulating hematopoietic progenitors in patients suffering from isolated Cutaneous Mastocytosis and from systemic Mastocytosis with skin lesions.

Mastocytosis is a rare disease caused by abnormal mast cell accumulation/proliferation. Its clinical features are very heterogeneous. Among adult patients, 15% present an isolated cutaneous mastocytosis (CM), while 85% of them present a systemic mastocytosis (SM) with cutaneous lesions. In addition, regardless of the diagnosis (i.e., CM or SM), it is frequent to observe mast cell-dependent symptoms of variable severity, ranging from gastrointestinal discomfort to life-threatening reactions. To date, the origin of such heterogeneous manifestations in adult patients is still elusive. Researchers hypothesize that the heterogeneity in mastocytosis symptoms might originate, at least in part, from a broad diversity of mast cell populations in patients. This study will aim to uncover heterogeneity of skin-resident mast cells and of blood circulating hematopoietic progenitors in patients suffering from isolated CM or SM with skin lesions. Patients with isolated CM and patients with SM with cutaneous involvement will be recruited from the Mastocytosis Expert Center of Toulouse.

Cluster of Differentiation (CD) 45+ cells from skin biopsies and CD 34+ cells from blood will be isolated by magnetic cell sorting for scRNAseq. Bioinformatics analysis pipeline will be used in order to analyze the cellular heterogeneity of skin lesions and blood from CM and SM patients by comparing their transcriptomic signatures. Using trajectories analysis, the researchers will then deduce infer a differentiation pathway between blood progenitors and cutaneous mast cells at the patient level. Researchers will then confirm the expression of identified relevant biomarkers by highly multiplexed imaging in frozen skin biopsies from CM patients and from SM patients.

Study of Cellular Heterogeneity in Patients With Mastocytosis

Study of Cellular Heterogeneity in Patients With Mastocytosis (MastCellHet) Mastocytosis Cell Heterogeneity

through advanced imaging techniques (multiplexed imaging), marker in patients with isolated cutaneous mastocytosis and systemic mastocytosis will be identified compared with control sample

through advanced imaging techniques (multiplexed imaging), marker in patients with isolated cutaneous mastocytosis will be identified compared with control sample

through advanced imaging techniques (multiplexed imaging), marker in patients with systemic mastocytosis will be identified compared with control sample

This study aims to examine the diversity of CD 45+ cells in the skin and CD 34+ cells in the circulating blood in patients. The approach used will be single cell sequencing (scRNAseq) to identify the transcriptomic profiles of the different cell populations in these two types of mastocytosis.

This part of the study will focus on analyzing common or differential genetic transcripts between patients with isolated cutaneous mastocytosis and those with systemic mastocytosis. The aim is to understand the underlying molecular differences between these two forms of the disease.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Stem Cell Transplantation to Treat Systemic Mastocytosis	NCT00006413	Mastocytosis	Stem cell trans...	2 Years - 80 Years	National Institutes of Health Clinical Center (CC)
Cytokine Production Patterns in Patients With Systemic Mastocytosis Compared With Atopic Dermatitis and Healthy Individuals	NCT00001760	Atopic Dermatit... Healthy Mastocytosis		-	National Institutes of Health Clinical Center (CC)
Study of Mast Cell Precursors	NCT00001756	Mastocytosis Healthy Volunte...		18 Years - 70 Years	National Institutes of Health Clinical Center (CC)
Stem Cell Transplantation to Treat Systemic Mastocytosis	NCT00006413	Mastocytosis	Stem cell trans...	2 Years - 80 Years	National Institutes of Health Clinical Center (CC)
Cause and Natural Course of Pediatric-Onset Mastocytosis	NCT00050193	Mastocytosis		- 21 Years	National Institutes of Health Clinical Center (CC)
Study of Cellular Heterogeneity in Patients With Mastocytosis	NCT06432556	Mastocytosis	scRNAseq two Skin biopsi... one Skin biopsi...	18 Years -	University Hospital, Toulouse
Cause and Natural Course of Pediatric-Onset Mastocytosis	NCT00050193	Mastocytosis		- 21 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for mast cells

Every month we try and update this database with for mast cells 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 mast cells

Every month we try and update this database with for mast cells 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 mast cells 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.