Symptoms and General Pathology

All Conditions

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Immune System Diseases

Heart and Blood Diseases

Rare Diseases

Syndrome

Anemia

Leukemia

Anemia, Aplastic

Cytopenia

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Myelodysplastic Syndromes

Hemoglobinuria

Hemoglobinuria, Paroxysmal

Bone Marrow Failure Disorders

Pancytopenia

Red-Cell Aplasia, Pure

Purpura

Purpura, Thrombocytopenic

Leukemia, Large Granular Lymphocytic

Leukemia, Lymphoid

Neoplasms by Histologic Type

Hematologic Diseases

Bone Marrow Diseases

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Blood Coagulation Disorders

Hemorrhage

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Proteinuria

Urination Disorders

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Urological Manifestations

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hemolysis

Anemia, Hemolytic

Thrombotic Microangiopathies

Thrombocytopenia

Blood Platelet Disorders

Paroxysmal Nocturnal Hemoglobinuria

Pure Red Cell Aplasia

Acquired Pure Red Cell Aplasia

Aggressive NK Cell Leukemia

Jaroslaw P. Maciejewski, MD, PhD

Bone marrow failure syndromes (BMFS) are rare disorders characterized by dysfunctional hematopoietic stem cells, which give rise to all red and white blood cells. The deficiency of blood cells, or cytopenia, caused by this malfunction leads to an assortment of diseases and disorders, all of which are characterized as BMFS. Because these diseases are rare, conducting research on them is difficult, and standards of treatment for most BMFS have yet to be developed. This study will collect clinical and laboratory data from people with BMFS to identify the characteristics and biological markers associated with these diseases over time. This information will assist doctors and researchers to develop better therapies and diagnostic tests that will help improve the management of BMFS and cytopenias.

BMFS result from hematopoietic progenitor or stem cell failure within the bone marrow. Specific causes of this problem, however, have been difficult to identify, as BMFS occur sporadically. For the same reason, few studies have been conducted to find out more about these diseases and to develop more appropriate and effective therapies. Aplastic anemia (AA) is the most common of all BMFS. Other types of BMFS include the following: myelodysplastic syndrome (MDS); paroxysmal nocturnal hemoglobinuria (PNH); pure red cell aplasia (PRCA); amegakaryocytic thrombocytopenic purpura (ATP); and large granular lymphocyte leukemia (LGL leukemia). Though AA is the most common of the BMFS, all BMFS are closely related in terms of their symptoms and characteristics. This study will collect clinical and laboratory data from people with BMFS to identify the characteristics and biological markers specific to each disease as it evolves. This information will assist doctors and researchers to devise better therapies and diagnostic tests that will help improve the management of BMFS and cytopenias.

Participants in this observational study will report to the study site for an initial screening visit, followed by study visits every 6 months for at least 5 years. At each visit, participants will be interviewed and examined by a physician. Laboratory tests, including blood collection and a bone marrow aspirate, will also be performed. Data collected for this study's database will be used to determine the prevalence of clinical events and laboratory abnormalities over the course of disease, to study the evolution of disease parameters and symptoms, and to evaluate current therapies and diagnostic tests.

Residual samples from peripheral blood and bone marrow aspiration/biopsies

Identifying Characteristics of Bone Marrow Failure Syndromes

Screening Protocol and Longitudinal Study of Bone Marrow Failure Syndromes and Cytopenias

Rare Diseases Clinical Research Network

Office of Rare Diseases (ORD)

Jaroslaw Maciejewski, MD, PhD

Lymphoma

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Hematologic Neoplasms

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Leukemia, Myelomonocytic, Juvenile

Myeloproliferative Disorders

Chronic Disease

Disease Attributes

Myelodysplastic-Myeloproliferative Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Chronic Graft Versus Host Disease

Acute Non Lymphoblastic Leukemia

Chronic Myeloid Leukemia

Acute Graft Versus Host Disease

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Myeloproliferative Disorders

Myelodysplastic/myeloproliferative Disease

All Drugs and Chemicals

Antineoplastic Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Anti-Infective Agents

Antibodies

Cyclophosphamide

Methotrexate

Cyclosporine

Cyclosporins

Immunoglobulins

Thiotepa

Immunologic Factors

An infusion of HLA matched unrelated bone marrow or peripheral blood stem cells.

Allogeneic Stem Cell Transplantation

Participants received a standard conditioning regimen consisting of total body irradiation, cyclophosphamide, thiotepa and ATG. GVHD prophylaxis consisted of cyclosporine and Methotrexate.

Chemotherapy and antibodies

Gregory Hale, M.D.

Childhood leukemias which cannot be cured by chemotherapy alone may be effectively treated by allogeneic bone marrow transplantation. Moreover, for patients with chronic myelogenous leukemia (CML), allogeneic hematopoietic stem cell transplantation (HSCT) is the only proven curative modality of treatment. Patients who have received hematopoietic stem cells from an HLA matched sibling donor have proven to be less at risk for disease relapse and regimen related toxicity. However, about 70% of patients in need of HSCT do not have an HLA matched sibling donor. This necessitates the search for alternative donors, which may increase the risk of a poor outcome.

The nature of the hematopoietic stem cell graft has been implicated as a primary factor determining these outcomes. The standard stem cell graft has been unmanipulated bone marrow, but recently several advantages of T-lymphocyte depleted bone marrow and mobilized peripheral blood progenitor cells (PBPC) have been demonstrated. However, T-cell depletion may increase the risk of infectious complications and leukemic recurrence while an unmanipulated stem cell graft may increase the risk of graft vs. host disease (GVHD). A key element in long range strategies in improving outcomes for patients undergoing matched unrelated donor (MUD) HSCT is to provide the optimal graft.

The primary objective of this clinical trial is to estimate the incidence of acute GVHD in pediatric patients with hematologic malignancies who receive HSCT with an unmanipulated marrow graft. The results of this study can be used as the foundation for future trials related to engineering unrelated donor graft.

Secondary outcome evaluations for this clinical study include the following:

* To estimate the overall survival in patients with high risk hematological malignancies who receive a HSCT with an unmanipulated marrow graft or a peripheral blood stem cell graft
* To estimate disease-free survival and relapse rates
* To estimate the rates of chronic GvHD and graft failure
* To estimate the incidence of non-hematologic peri-transplant regimen-related toxicity and regimen-related mortality in the first 100 days after transplantation
* To estimate the time to neutrophil and platelet engraftment after transplantation
* To determine the degree of NK cell and T-cell immune reconstitution at 30 days and 100 days post-transplant
* To estimate the incidence of EBV reactivation or post-transplant lymphoproliferative disease (PTLPD)
* To determine the pharmacokinetics of anti-thymocyte globulin (rATG) in patients receiving allogeneic transplantation and the development of rATG antibodies

Originally this study began as a randomized comparison between unmanipulated bone marrow and T-cell depleted bone marrow utilizing the investigational CliniMACS selection system. The hypothesis to be tested at the time was that the incidence of severe acute GvHD was significantly reduced in children who received HSCT with a T-cell depleted bone marrow stem cell graft as compared to those receiving an unmanipulated graft. Approximately midway through the study the evidence indicated that although the incidence of severe acute GvHD with T-cell depletion was low, it was not significantly lower than the standard treatment of unmanipulated bone marrow. Therefore the study was amended to remove the T-cell depleted arm and continue accrual to one arm providing all patients with an unmanipulated bone marrow stem cell graft. The primary objective then being to determine if the true incidence of severe acute GvHD was below 15% as reported. The observational group receiving PBPC remained open for those patients whose donors or donor centers chose to provide PBPC in lieu of bone marrow. Only one such patient was assigned to this group; therefore, no valid conclusions can be formulated.

Intervention analysis was based on those patients who received an unmanipulated stem cell product only. For this study, the investigators had requested bone marrow for all study subjects. However, the final determination of the source of the hematopoietic stem cells, bone marrow or peripheral blood, was at the discretion of the donor and the donor center. Those participants who received a peripheral blood stem cell product were followed in the observational group only. All participants, whether recipients of a bone marrow or blood stem cell product, received the same preparative conditioning regimen

Stem Cell Transplantation for Patients With Hematologic Malignancies

Hematopoietic Stem Cell Transplantation Using Matched Unrelated Donor Peripheral Blood or Bone Marrow for Patients With Hematologic Malignancies

St. Jude Children's Research Hospital

Gregory Hale, MD / Principal Investigator

Multiple Myeloma

Neoplasms, Plasma Cell

Primary Myelofibrosis

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Melphalan

Busulfan

Alemtuzumab

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunosuppressive Agents

Antineoplastic Agents, Immunological

Three drug regimen using busulfan, and melphalan, and alemtuzumab.

intravenous busulfan 3.2 mg/kg/dose daily for 2 days, on days -5 and -4 (i.e., 5 and 4 days, respectively, before PBSCT).

intravenous melphalan 100 mg/m2 on day -3.

intravenous alemtuzumab 30 mg/dose for 2 days, on days -2 and -1.

busulfan, and melphalan, and alemtuzumab

Andrew M Yeager, MD

The purpose of this study is to look at whether the combination of lower-dose chemotherapy with two chemotherapy (anti-cancer) drugs, called busulfan and melphalan, and an antibody medication called alemtuzumab (Campath®), can prevent rejection of donor blood stem cells so that those cells take hold and build a healthy new blood cell factory after transplant. The study will also look at the safety of the combination of drugs and of the transplant of peripheral blood stem cells from a healthy relative or an unrelated donor.

Transplantation of related or unrelated allogeneic peripheral blood stem cells (PBSCs) after administration of a reduced-intensity regimen of busulfan, melphalan and alemtuzumab will be associated with satisfactory engraftment and acceptable post-transplant non-relapse mortality.

Reduced Intensity Allogeneic PBSCT to Treat Hematologic Malignancies and Hematopoietic Failure States

A Phase II Study of Reduced-Intensity Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT) for Treatment of Hematologic Malignancies and Hematopoietic Failure States

To determine the efficacy of related or unrelated allogeneic PBSC transplantation (PBSCT) using a preparative regimen of busulfan, melphalan and alemtuzumab, as measured by durable donor lymphohematopoietic cell engraftment. The primary efficacy endpoint is the presence of donor lymphohematopoietic chimerism (defined as at least 50% donor cells in the peripheral blood) in peripheral blood by day +100 (i.e., 100 days after allogeneic PBSCT).

To determine the safety of related or unrelated allogeneic PBSCT using a preparative regimen of busulfan, melphalan and alemtuzumab. The primary safety endpoint is non-relapse mortality at day +100.

University of Arizona

Three drug regimen using busulfan, and melphalan, and alemtuzumab.

Busulfan, and melphalan, and alemtuzumab: intravenous busulfan 3.2 mg/kg/dose daily for 2 days, on days -5 and -4 (i.e., 5 and 4 days, respectively, before PBSCT).

Intravenous melphalan 100 mg/m2 on day -3.

Intravenous alemtuzumab 30 mg/dose for 2 days, on days -2 and -1.

Busulfan, and Melphalan, and Alemtuzumab

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

United States

Region of Enrollment

Program Coordinator

Data were collected but could not be analyzed. PI for this study has retired and any data that were gathered, are lost. No data are available for this assessment

Number of Participants With Presence of Donor Lymphohematopoietic Chimerism (Defined as at Least 50% Donor Cells in the Peripheral Blood) in Peripheral Blood by Day +100 (i.e., 100 Days After Allogeneic PBSCT).

Data were collected but could not be analyzed. PI for this study has retired and any data that were gathered, are lost. No data are available for this assessment.

Number of Participants With Relapse-free Survival.

Number of Participants With Event-free Survival.

Number of Participants With Overall Survival.

Overall Study

Leukemia, Lymphocytic, Chronic, B-Cell

Hodgkin Disease

Leukemia, B-Cell

Aplastic Anemia

Chronic Lymphocytic Leukemia

Hodgkin Lymphoma

Basiliximab

Basiliximab will be given by IV on Day +7 post transplant for recipients of matched unrelated cells. Basiliximab will be given by IV on Day +9 post transplant for recipients of matched related cells.

Basiliximab given 1 time on Day +7 or Day +9.

Robert Nelson, MD

The purpose of this study is to compare the effects (good and bad) of the medication basiliximab in combination with cyclosporine (investigational therapy) for the prevention of a complication of bone marrow transplantation known as graft-versus-host disease (GVHD). GVHD is a complication in which the cells of the transplanted bone marrow react against organs and tissues.

This study is for patients with a blood condition or myelodysplasia (bone marrow disease) which has either not responded to treatment or is not treatable by conventional/routine medical treatments. Bone marrow transplantation is a medical treatment that involves giving high doses of chemotherapy followed by the transplantation of the blood-forming and immune cells from a relative or from a "matched" unrelated person through the National Marrow Donor Program, in an attempt to cure disease in the recipient (the person receiving the donated cells). Nonmyeloablative (bone-marrow preservation) bone marrow transplantation is a relatively new technique in which lower than usual doses of chemotherapy are given before transplantation, in hopes of reducing adverse side effects of the chemotherapy in transplant patients. Nonmyeloablative bone marrow transplantation has several advantages which doctors have determined are beneficial for this condition.

This research is being done because the complication of graft-versus-host disease can be bad for a person and there is no completely safe and effective way to prevent this complication. We know that cyclosporine helps but would like to know if the addition of basiliximab, given with cyclosporine, will decrease the incidence and/or severity of graft-versus-host disease after a transplant known as nonmyeloablative or "mini" transplant.

Basiliximab #2: In-Vivo Activated T-Cell Depletion to Prevent Graft-Versus_Host Disease (GVHD) After Nonmyeloablative Allotransplantation for the Treatment of Blood Cancer

Basiliximab #2: In-Vivo Activated T-Cell Depletion to Prevent GVHD After Nonmyeloablative Allotransplantation for the Treatment of Blood Cancer

The percent of patients where a patient experienced a Grade 3 or 4 acute GVHD

Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. Patients who did not have neutrophil engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided.

Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of seven consecutive days after transplantation during which the platelet count is at least 20 x109/l without transfusion support. Patients who did not have platelet engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided.

Indiana University School of Medicine

Patients administered 40 mg of basiliximab as a single intravenous dose on day +7, +8, or +9 following infusion of allogeneic peripheral blood hematopoietic cells

Overall

Age, Continuous

Race (NIH/OMB)

Dr. Robert Nelson

All patients enrolled and received treatment

Grade 3-4 Acute GVHD Rate

All patients enrolled and received treatment, excluding the patient who entered after the stopping rule was met.

Time to Neutrophil Engraftment

Time to Platelet Engraftment

Amino Acids

Mechlorethamine

Phenylalanine

Non-myeloablative preparative regimen (reduced-intensity) of busulfan, melphalan and alemtuzumab followed by a haploidentical-related peripheral blood stem cell transplant.

Days -5 and -4: IV busulfan 3.2 mg/kg/dose daily for 2 days

Day -3: IV melphalan 100 mg/m2 as a single dose

Days -2 and -1: IV alemtuzumab 30 mg/dose daily for 2 days

Day 0: Transplantation of haploidentical related allogeneic peripheral blood stem cells (PBSCs)- target cell dose 10 x 106 donor CD34+ cells per kilogram of recipient weight

haploidentical allogeneic PBSC transp

The purpose of this study is to transplant haploidentical related peripheral blood stem cells (PBSCs) that come from a relative such as a parent, sibling, a child or other relative who has a half-matched tissue type with the recipient (rather than being completely matched) following administration of a reduced-intensity regimen of busulfan, melphalan and alemtuzumab.

Fewer than 35% of patients who might benefit from allogeneic HCT have an HLA-identical sib. Transplantation of peripheral blood stem cells (PBSCs) or bone marrow (BM)from HLA-matched or one-locus mismatch unrelated volunteer donors may be an alternative in some patients who lack HLA-matched sib donors. Despite increasing numbers of volunteer unrelated donors in national and international registries, identification of suitable unrelated donors who are matched with the recipient at all HLA-A, -B, -C and -DRB1 loci (8/8 HLA match) or mismatched at one of those loci (7/8 HLA match) is still challenging, especially for patients who are African-American or multiracial. Additionally, the 3- to 4-month delay between initiation of unrelated donor search to HCT is unacceptably long in patients with aggressive hematologic malignancies that are likely to relapse or progress during that interval. Transplantation of single or dual unrelated umbilical cord blood cells (UCB) units is another alternative, although problems with inadequate cell doses, delayed engraftment, graft rejection and infection persist in adult recipients of unrelated UCB transplants.

This is a phase II single-arm open-label study to evaluate the efficacy and safety of haploidentical related allogeneic PBSCT using a nonmyeloablative preparative regimen of intravenous busulfan (Busulfex®), intravenous melphalan (Alkeran®) and intravenous alemtuzumab (Campath®) in subjects who are candidates for related or unrelated allogeneic hematopoietic cell transplantation (HCT; transplantation of bone marrow or PBSCs) but who lack histocompatible related or unrelated donors. This study will also evaluate immunological reconstitution following haploidentical PBSCT by measurement of circulating T cell receptor excision circle (TREC)-positive cells, an indicator of thymic output. Systematic analyses of TREC-positive cells have not been performed in recipients of haploidentical PBSCT after the preparative regimen described in this protocol.

Peripheral Blood Stem Cell Transplantation (PBSCT)From Haploidentical Related Donors

A Phase II Study of Peripheral Blood Stem Cell Transplantation (PBSCT)From Haploidentical Related Donors for Treatment of Hematologic Malignancies and Hematopoietic Failure States

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Identifying Characteristics of Bone Marrow Failure Syndromes	NCT00315419	Bone Marrow Fai... Anemia, Aplasti... Myelodysplastic... Hemoglobinuria,... Red-Cell Aplasi... Purpura, Thromb... Leukemia, Lymph...		11 Years -	Office of Rare Diseases (ORD)
Stem Cell Transplantation for Patients With Hematologic Malignancies	NCT00152139	Acute Lymphobla... Acute Myelocyti... Chronic Myeloid... Juvenile Myelom... Myelodysplastic... Hemoglobinuria,... Non-Hodgkin Lym...	Allogeneic Stem... Chemotherapy an...	2 Years - 21 Years	St. Jude Children's Research Hospital
Stem Cell Transplantation for Patients With Hematologic Malignancies	NCT00152139	Acute Lymphobla... Acute Myelocyti... Chronic Myeloid... Juvenile Myelom... Myelodysplastic... Hemoglobinuria,... Non-Hodgkin Lym...	Allogeneic Stem... Chemotherapy an...	2 Years - 21 Years	St. Jude Children's Research Hospital
Reduced Intensity Allogeneic PBSCT to Treat Hematologic Malignancies and Hematopoietic Failure States	NCT00997386	Hematologic Neo... Multiple Myelom... Anemia, Aplasti... Hemoglobinuria,... Myelofibrosis	busulfan, and m...	18 Years - 75 Years	University of Arizona
Reduced Intensity Allogeneic PBSCT to Treat Hematologic Malignancies and Hematopoietic Failure States	NCT00997386	Hematologic Neo... Multiple Myelom... Anemia, Aplasti... Hemoglobinuria,... Myelofibrosis	busulfan, and m...	18 Years - 75 Years	University of Arizona
Basiliximab #2: In-Vivo Activated T-Cell Depletion to Prevent Graft-Versus_Host Disease (GVHD) After Nonmyeloablative Allotransplantation for the Treatment of Blood Cancer	NCT00975975	Acute Myelogeno... Acute Lymphocyt... Chronic Myeloge... Chronic Lymphoc... Myelodysplasia Non-Hodgkin's L... Hodgkin's Disea... Multiple Myelom... Myelofibrosis Anemia, Aplasti... Hemoglobinuria,...	Basiliximab	18 Years -	Indiana University
Basiliximab #2: In-Vivo Activated T-Cell Depletion to Prevent Graft-Versus_Host Disease (GVHD) After Nonmyeloablative Allotransplantation for the Treatment of Blood Cancer	NCT00975975	Acute Myelogeno... Acute Lymphocyt... Chronic Myeloge... Chronic Lymphoc... Myelodysplasia Non-Hodgkin's L... Hodgkin's Disea... Multiple Myelom... Myelofibrosis Anemia, Aplasti... Hemoglobinuria,...	Basiliximab	18 Years -	Indiana University
Peripheral Blood Stem Cell Transplantation (PBSCT)From Haploidentical Related Donors	NCT00618969	Hematologic Neo... Anemia, Aplasti... Hemoglobinuria,... Multiple Myelom...	haploidentical ...	18 Years - 75 Years	University of Arizona

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