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Sponsors and Collaborators: |
Roswell Park Cancer Institute National Cancer Institute (NCI) |
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Information provided by: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00003662 |
RATIONALE: Umbilical cord blood transplantation may be able to replace cells destroyed by chemotherapy or radiation therapy.
PURPOSE: Phase II trial to study the effectiveness of umbilical cord blood transplantation in treating patients who have hematologic cancer or other hematologic or metabolic diseases.
Condition | Intervention | Phase |
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Graft Versus Host Disease Leukemia Myelodysplastic Syndromes Thymoma and Thymic Carcinoma |
Biological: anti-thymocyte globulin Drug: busulfan Drug: cyclophosphamide Drug: cyclosporine Drug: melphalan Drug: methylprednisolone Procedure: umbilical cord blood transplantation Radiation: radiation therapy |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment |
Official Title: | A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Adults and Children With Bone Marrow Failure Syndromes or Inherited Metabolic or Hematologic Diseases |
Estimated Enrollment: | 90 |
Study Start Date: | August 1998 |
OBJECTIVES: I. Determine the rates of durable engraftment in patients with severe aplastic anemia, myelodysplastic syndrome, inborn errors of metabolism, or inherited hematopoietic disorders refractory to medical management, who are undergoing high dose chemoradiotherapy followed by unrelated cord blood (UCB) transplantation. II. Determine the incidence and severity of acute and chronic graft-versus-host disease in these patients. III. Monitor overall and event-free survival of these patients. IV. Evaluate rate and quality of immunologic reconstitution of these patients. V. Determine whether nucleated cell or progenitor cell content of the graft is predictive of engraftment.
OUTLINE: This is a multicenter study. Patients are stratified according to low vs high weight. Patients with severe aplastic anemia, myelodysplastic syndrome, or bone marrow failure receive cyclophosphamide IV over 1 hour on days -6 to -3 or melphalan IV over 20 minutes on days -4 to -2, antithymocyte globulin (ATG) IV over 4 hours or methylprednisolone IV over 1 hour twice a day on days -3 to -1, and total lymphoid irradiation on day -1. On day 0, patients receive umbilical cord blood (UCB) infusion. Patients with inborn errors of metabolism or inherited hematopoietic disorders receive oral busulfan every 6 hours on days -9 to -6, cyclophosphamide IV over
1 hour on days -5 to -2 or melphalan IV over 20 minutes on days -4 to -2, and ATG IV over 4 hours or methylprednisolone IV over 1 hour on days -3 to -1. On day 0, patients receive UCB infusion. Patients with Fanconi's anemia receive ATG IV over 4 hours or methylprednisolone IV over 1 hour on days -6 to -1, cyclophosphamide IV over 1 hour on days -5 to -2, thoracoabdominal irradiation on day -1, and then the UCB infusion on day 0. Patients also receive cyclosporine and methylprednisolone beginning on day -2 and continuing as necessary as graft-versus-host disease prophylaxis. Patients are followed indefinitely for survival and late toxicity.
PROJECTED ACCRUAL: A total of 4-90 patients will be accrued for this study within 5 years.
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of one of the following: - Severe aplastic anemia with bone marrow cellularity less than 20% and at least 2 of the following criteria: Granulocyte count less than 500/mm3 Platelet count less than 20,000/mm3 Reticulocyte count less than 50,000/mm3 Etiologies may be Fanconi's anemia, hypoplastic leukemia, monosomy 7, drug exposure (chloramphenicol, NSAIDS), viral exposure (EBV, hepatitis, parvovirus, HIV), nutritional deficiencies, thymoma, paroxysmal nocturnal hemoglobinuria, and amegakaryocytic thrombocytopenia - Myelodysplastic syndrome (MDS) that is refractory to medical management or with cytogenetic abnormalities predictive of transformation into acute leukemia, including 5q-, 7q-, monosomy 7, and trisomy 8 De novo primary or therapy-related secondary MDS Refractory anemia or refractory anemia with ringed sideroblasts only - Inherited hematopoietic disorders that are refractory to medical management Severe combined immunodeficiency Familial erythrophagocytic lymphohistiocytosis Wiskott-Aldrich syndrome Kostmann's syndrome (infantile agranulocytosis) Chronic granulomatous disease Leukocyte adhesion deficiency Chediak-Higashi syndrome Paroxysmal nocturnal hemoglobinuria Fanconi's anemia Dyskeratosis congenita Diamond-Blackfan anemia Amegakaryocytic thrombocytopenia Osteopetrosis Gaucher's disease Lesch-Nyhan syndrome Mucopolysaccharidoses Lipidoses Must also meet all the following conditions: No HLA-ABC/DR identical related bone marrow or UCB donor No 5/6 antigen matched related bone marrow or UCB donor Condition precludes waiting to search and find a donor in the National Marrow Donor Registry Must have backup autologous or haploidentical related marrow Must have available serologic match umbilical cord blood unit in the New York Blood Center's Placental Blood Project
PATIENT CHARACTERISTICS: Age: Not specified Performance status: Zubrod 0-1 OR Karnofsky or Lansky 80-100% Life expectancy: At least 3 months Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 2.0 mg/dL ALT/AST no greater than 4 times normal Renal: Creatinine no greater than 2.0 mg/dL Creatinine clearance at least 50 mL/min Cardiovascular: Shortening fraction or ejection fraction at least 80% of normal for age Pulmonary: FVC and FEV1 at least 60% predicted for age Adults: DLCO at least 60% predicted Other: No active concurrent malignancy No active infections at time of backup bone marrow harvest or pretransplant cytoreduction Not pregnant or nursing Negative pregnancy test HIV negative
PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No concurrent cytotoxic chemotherapy Endocrine therapy: No concurrent immunosuppressive medications Radiotherapy: No concurrent radiotherapy Surgery: Not specified
United States, Florida | |
Division of Pediatric Surgery | |
Jacksonville, Florida, United States, 32207 | |
H. Lee Moffitt Cancer Center and Research Institute | |
Tampa, Florida, United States, 33612 | |
University of Florida Health Science Center | |
Gainesville, Florida, United States, 32610-0296 | |
United States, Illinois | |
Rush-Presbyterian-St. Luke's Medical Center | |
Chicago, Illinois, United States, 60612 | |
University of Chicago Cancer Research Center | |
Chicago, Illinois, United States, 60637 | |
United States, Louisiana | |
Children's Hospital of New Orleans | |
New Orleans, Louisiana, United States, 70118 | |
United States, Missouri | |
Cardinal Glennon Children's Hospital | |
Saint Louis, Missouri, United States, 63104 | |
United States, New Jersey | |
Hackensack University Medical Center | |
Hackensack, New Jersey, United States, 07601 | |
United States, New York | |
New York Blood Center | |
New York, New York, United States, 10021 | |
Roswell Park Cancer Institute | |
Buffalo, New York, United States, 14263-0001 | |
United States, North Carolina | |
Duke Comprehensive Cancer Center | |
Durham, North Carolina, United States, 27710 | |
Lineberger Comprehensive Cancer Center, UNC | |
Chapel Hill, North Carolina, United States, 27599-7295 | |
United States, Pennsylvania | |
St. Christopher's Hospital for Children | |
Philadelphia, Pennsylvania, United States, 19134-1095 | |
United States, South Carolina | |
Medical University of South Carolina | |
Charleston, South Carolina, United States, 29425-0721 | |
University of South Carolina School of Medicine | |
Columbia, South Carolina, United States, 29203 |
Study Chair: | Barbara Jean Bambach, MD | Roswell Park Cancer Institute |
Study ID Numbers: | CDR0000066755, RPCI-RP-9803, NCI-G98-1486 |
Study First Received: | November 1, 1999 |
Last Updated: | February 6, 2009 |
ClinicalTrials.gov Identifier: | NCT00003662 History of Changes |
Health Authority: | United States: Federal Government |
noninvasive thymoma and thymic carcinoma recurrent thymoma and thymic carcinoma refractory anemia refractory anemia with ringed sideroblasts de novo myelodysplastic syndromes |
previously treated myelodysplastic syndromes secondary myelodysplastic syndromes graft versus host disease childhood myelodysplastic syndromes |
Thoracic Neoplasms Anti-Inflammatory Agents Anti-Infective Agents Cyclosporine Methylprednisolone Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Antiemetics Cyclosporins Hormones Refractory Anemia Graft Versus Host Disease Preleukemia Anemia, Refractory Neoplasm Metastasis |
Metabolic Disorder Methylprednisolone Hemisuccinate Metabolic Diseases Antineoplastic Agents, Hormonal Hematologic Diseases Pancytopenia Glucocorticoids Carcinoma Neoplasms, Glandular and Epithelial Melphalan Precancerous Conditions Hematologic Neoplasms Immunologic Factors Prednisolone acetate Cyclophosphamide |
Thoracic Neoplasms Anti-Inflammatory Agents Anti-Infective Agents Cyclosporine Molecular Mechanisms of Pharmacological Action Methylprednisolone Physiological Effects of Drugs Hormones, Hormone Substitutes, and Hormone Antagonists Antiemetics Hormones Cyclosporins Preleukemia Neoplasms by Site Pathologic Processes Therapeutic Uses |
Dermatologic Agents Methylprednisolone Hemisuccinate Antineoplastic Agents, Hormonal Immune System Diseases Hematologic Diseases Glucocorticoids Carcinoma Neoplasms Neoplasms, Complex and Mixed Neoplasms, Glandular and Epithelial Precancerous Conditions Immunologic Factors Antineoplastic Agents Prednisolone acetate Cyclophosphamide |