Blood and Lymph Conditions

All Conditions

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Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Rare Diseases

Thrombocytopenia

Syndrome

Leukemia

Anemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Leukemia, Myeloid, Chronic-Phase

Neutropenia

Bone Marrow Diseases

Hematologic Diseases

Fanconi Syndrome

Fanconi Anemia

Anemia, Diamond-Blackfan

Neoplasms by Histologic Type

Myeloproliferative Disorders

Chronic Disease

Disease Attributes

Blood Platelet Disorders

Cytopenia

Agranulocytosis

Leukopenia

Leukocyte Disorders

Anemia, Hypoplastic, Congenital

Anemia, Aplastic

Bone Marrow Failure Disorders

Pancytopenia

Congenital Bone Marrow Failure Syndromes

Genetic Diseases, Inborn

DNA Repair-Deficiency Disorders

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Kidney Diseases

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Female Urogenital Diseases and Pregnancy Complications

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Red-Cell Aplasia, Pure

Myeloid Leukemia

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Acute Graft Versus Host Disease

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Diamond-Blackfan Anemia

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Congenital Amegakaryocytic Thrombocytopenia

Chronic Myeloproliferative Disorders

Pure Red Cell Aplasia

Antineoplastic Agents

All Drugs and Chemicals

Fludarabine

Fludarabine phosphate

Busulfan

Antilymphocyte Serum

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Alkylating Agents

Antineoplastic Agents, Alkylating

anti-thymocyte globulin

busulfan

fludarabine phosphate

allogeneic bone marrow transplantation

peripheral blood stem cell transplantation

umbilical cord blood transplantation

radiation therapy

Morton J. Cowan, MD

RATIONALE: Drugs used in chemotherapy, such as busulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. A donor peripheral blood, bone marrow , or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin before the transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects of busulfan, antithymocyte globulin, and fludarabine when given together with a donor stem cell transplant in treating young patients with blood disorders, bone marrow disorders, chronic myelogenous leukemia in first chronic phase, or acute myeloid leukemia in first remission.

OBJECTIVES:

Primary

* Determine the efficacy, in terms of graft rejection at 4 weeks, of a conditioning regimen comprising busulfan, anti-thymocyte globulin, and fludarabine followed by donor stem cell transplantation (SCT) in children with stem cell defects, marrow failure syndromes, chronic myelogenous leukemia in first chronic phase, or acute myeloid leukemia in first remission.
* Determine the pharmacokinetics of busulfan in children undergoing donor SCT.

Secondary

* Determine the toxicity of this regimen in these patients.
* Determine engraftment at 3, 6, 9, and 12 months and mixed chimerism in patients treated with this regimen.
* Determine overall and disease-free survival of patients treated with this regimen.

OUTLINE: Patients receive one of the following cytoreductive regimens:

* Regimen 1 (patients with an HLA genotypic matched sibling donor): Patients receive busulfan IV over 2 hours every 6 hours on days -9 to -6, fludarabine IV on days -5 to -2, and anti-thymocyte globulin (ATG) IV over 10 hours on days -3 to -1.
* Regimen 2 (patients with an HLA closely matched related \[not genotypic\] or unrelated donor): Patients receive busulfan and fludarabine as in regimen 1, and ATG IV over 10 hours on days -4 to -1.
* Regimen 3 (patients with Fanconi's anemia or severe aplastic anemia with genotypic matched sibling donor): Patients receive fludarabine as in regimen 1 and ATG as in regimen 2.
* Regimen 4 (patients with Fanconi's anemia who have a closely matched related \[not genotypic\] or unrelated donor): Patients undergo thoracoabdominal irradiation on day -6 and receive fludarabine as in regimen 1 and ATG as in regimen 2.

All patients undergo allogeneic bone marrow, umbilical cord blood, or peripheral blood stem cell transplantation on day 0.

After the completion of study treatment, patients are followed periodically for 20 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission

Bone Marrow Stem Cell Transplantation for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myeloid Leukemia in 1Remission

National Cancer Institute (NCI)

University of California, San Francisco

Professor

Immune System Diseases

Preleukemia

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Neoplasm Metastasis

Immunologic Deficiency Syndromes

Anemia, Refractory, with Excess of Blasts

Anemia, Refractory

Precancerous Conditions

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Childhood Acute Lymphoblastic Leukemia

Myelodysplastic Syndrome With Excess Blasts

Thiotepa

Receiving haplocompatible T cell depleted peripheral blood stem cell transplant

therapeutic allogeneic lymphocytes

thiotepa

allogeneic hematopoietic stem cell transplantation

in vitro-treated peripheral blood stem cell transplantation

total-body irradiation

RATIONALE: Giving chemotherapy and total body irradiation before a donor bone marrow transplant or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin and removing the T cells from the donor cells before transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects and best dose of donor T cells and antithymocyte globulin when given together with chemotherapy and total-body irradiation in treating young patients who are undergoing T-cell depleted donor stem cell transplant for myelodysplastic syndrome, leukemia, bone marrow failure syndrome, or severe immunodeficiency disease.

OBJECTIVES:

* Determine the efficacy and toxicity of stem cell-enriched, T-cell-depleted, haplocompatible allogeneic hematopoietic stem cell transplantation in children with high-risk myelodysplastic syndromes, high-risk leukemia, severe acquired or congenital cytopenias, or primary immunodeficiency diseases.
* Determine the toxicity of a fludarabine and thiotepa-containing regimen in combination with lower doses of antithymocyte globulin in these patients.
* Determine the engraftment rate in patients treated with this regimen.
* Define T-cell reconstitution in these patients.
* Determine the toxicity and effects of administering stem cell and T-cell boosts after transplantation on hematopoiesis and immune reconstitution in these patients.

OUTLINE: This is a dose-escalation study of donor CD3+ cells and antithymocyte globulin (ATG).

* Cytoreductive regimen: Patients undergo total body irradiation twice daily on days -9 to -7. Patients also receive fludarabine IV on days -6 to -2, thiotepa IV every 12 hours on day -6, and ATG IV on days -5 to -2.
* Transplantation: Patients undergo CD34-enriched, T-cell-depleted, haplocompatible allogeneic peripheral blood stem cell or bone marrow transplantation on day 0.
* Donor T-cell infusion:Patients with no active graft-vs-host disease and evidence of engraftment but low absolute CD34+ lymphocyte count at 12 weeks post transplant may receive donor CD3+ cells at 4-week intervals.
* Donor stem cell boost: Patients with engraftment but either cytokine or transfusion dependent at 12 weeks post transplant may receive a boost of donor CD34+ cells.

Cohorts of 3-6 patients receive escalating doses of donor CD3+ cells and ATG until the optimum is determined. The optimum dose is defined as the dose at which both engraftment and T-cell recovery occur, without dose-limiting toxicity, in ≥ 5 of 6 patients.

After the completion of study treatment, patients are followed periodically for 5 years and then every 5 years thereafter.

PROJECTED ACCRUAL: A total of 21 patients will be accrued for this study.

Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency Disease

Stem Cell Enriched, T Cell Depleted Haplocompatible Peripheral Blood Transplantation for Children With Myelodysplastic Disease, Leukemia, Marrow Failure Syndromes, or Severe Immunodeficiency Diseases

Digestive System Diseases

Skin and Connective Tissue Diseases

Hematologic Neoplasms

Hemoglobinuria

Anemia, Sideroblastic

Shwachman-Diamond Syndrome

Anemia, Hypochromic

Hemoglobinuria, Paroxysmal

Proteinuria

Urination Disorders

Urological Manifestations

Hemolysis

Anemia, Hemolytic

Exocrine Pancreatic Insufficiency

Pancreatic Diseases

Gastrointestinal Diseases

Metabolism, Inborn Errors

Lipid Metabolism, Inborn Errors

Lipid Metabolism Disorders

Lipomatosis

Lipomatosis, Multiple Symmetrical

Paroxysmal Nocturnal Hemoglobinuria

Multiple Symmetric Lipomatosis

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Micronutrients

Hematinics

Vitamins

Tacrolimus

Antibodies

Methotrexate

Thymoglobulin

Immunoglobulins

Immunoglobulins, Intravenous

gamma-Globulins

Rho(D) Immune Globulin

Treosulfan

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Calcineurin Inhibitors

Folinic Acid

Folate

Vitamin B9

CONDITIONING REGIMEN: Patients receive treosulfan IV over 120 minutes on days -6 to -4, fludarabine phosphate IV over 60 minutes on days -6 to -2, and rATG IV over 4-6 hours on days -4 to -2.

TRANSPLANTATION: Patients undergo bone marrow or peripheral blood stem cell transplant on day 0.

GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously beginning on day -2 and a taper beginning on day 180. Patients may also receive tacrolimus PO. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Patients undergo ECHO or MUGA during screening and undergo bone marrow biopsy and aspiration at baseline and follow up. Patients may optionally undergo blood sample collection throughout the trial.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission	NCT00305708	Congenital Ameg... Diamond-blackfa... Fanconi Anemia Leukemia Severe Congenit... Thrombocytopeni...	anti-thymocyte ... busulfan fludarabine pho... allogeneic bone... peripheral bloo... umbilical cord ... radiation thera...	- 17 Years	University of California, San Francisco
Donor Stem Cell Transplant in Treating Young Patients With Myelodysplastic Syndrome, Leukemia, Bone Marrow Failure Syndrome, or Severe Immunodeficiency Disease	NCT00295971	Congenital Ameg... Leukemia Myelodysplastic... Severe Congenit...	anti-thymocyte ... therapeutic all... fludarabine pho... thiotepa allogeneic bone... allogeneic hema... in vitro-treate... total-body irra...	1 Year - 17 Years	University of California, San Francisco
Treosulfan-Based Conditioning Regimen Before a Blood or Bone Marrow Transplant for the Treatment of Bone Marrow Failure Diseases (BMT CTN 1904)	NCT04965597	Bone Marrow Fai... Congenital Ameg... Congenital Pure... Hereditary Side... Paroxysmal Noct... Shwachman-Diamo... Hematologic Neo... Hematologic Neo... Hematologic Neo...	Treosulfan Fludarabine Pho... Tacrolimus Methotrexate Lapine T-Lympho... Peripheral Bloo... Allogeneic Bone... Quality-of-Life... Echocardiograph... Multigated Acqu... Bone Marrow Bio... Bone Marrow Asp... Biospecimen Col...	1 Year - 49 Years	Fred Hutchinson Cancer Center

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