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Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer or Other Hematologic or Metabolic Diseases

Primary Purpose

Graft Versus Host Disease, Leukemia, Myelodysplastic Syndromes

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
anti-thymocyte globulin
busulfan
cyclophosphamide
cyclosporine
melphalan
methylprednisolone
umbilical cord blood transplantation
radiation therapy
Sponsored by
Roswell Park Cancer Institute
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft Versus Host Disease focused on measuring 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

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Florida Health Science Center
  • Division of Pediatric Surgery
  • H. Lee Moffitt Cancer Center and Research Institute
  • Rush-Presbyterian-St. Luke's Medical Center
  • University of Chicago Cancer Research Center
  • Children's Hospital of New Orleans
  • Cardinal Glennon Children's Hospital
  • Hackensack University Medical Center
  • Roswell Park Cancer Institute
  • New York Blood Center
  • Lineberger Comprehensive Cancer Center, UNC
  • Duke Comprehensive Cancer Center
  • St. Christopher's Hospital for Children
  • Medical University of South Carolina
  • University of South Carolina School of Medicine

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
March 3, 2011
Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003662
Brief Title
Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer or Other Hematologic or Metabolic Diseases
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2011
Overall Recruitment Status
Completed
Study Start Date
August 1998 (undefined)
Primary Completion Date
January 2001 (Actual)
Study Completion Date
January 2001 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Roswell Park Cancer Institute
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease, Leukemia, Myelodysplastic Syndromes, Thymic Carcinoma
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
anti-thymocyte globulin
Intervention Type
Drug
Intervention Name(s)
busulfan
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Type
Drug
Intervention Name(s)
methylprednisolone
Intervention Type
Procedure
Intervention Name(s)
umbilical cord blood transplantation
Intervention Type
Radiation
Intervention Name(s)
radiation therapy

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barbara Jean Bambach, MD
Organizational Affiliation
Roswell Park Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
University of Florida Health Science Center
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610-0296
Country
United States
Facility Name
Division of Pediatric Surgery
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32207
Country
United States
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Rush-Presbyterian-St. Luke's Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Chicago Cancer Research Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Children's Hospital of New Orleans
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70118
Country
United States
Facility Name
Cardinal Glennon Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263-0001
Country
United States
Facility Name
New York Blood Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Lineberger Comprehensive Cancer Center, UNC
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599-7295
Country
United States
Facility Name
Duke Comprehensive Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
St. Christopher's Hospital for Children
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19134-1095
Country
United States
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425-0721
Country
United States
Facility Name
University of South Carolina School of Medicine
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States

12. IPD Sharing Statement

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Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer or Other Hematologic or Metabolic Diseases

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