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Pilot Study Of Unrelated UCB Transplant for Non-Malignant Hematologic Conditions

Primary Purpose

Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
anti-thymocyte globulin
busulfan
cyclophosphamide
melphalan
methylprednisolone
bone marrow ablation with stem cell support
umbilical cord blood transplantation
radiation therapy
Sponsored by
Case Comprehensive Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring refractory anemia, refractory anemia with ringed sideroblasts, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, atypical chronic myeloid leukemia, myelodysplastic/myeloproliferative disease, unclassifiable, childhood myelodysplastic syndromes

Eligibility Criteria

undefined - 55 Years (Child, Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of severe aplastic anemia based on bone marrow cellularity of less than 20% Must meet at least two of the following criteria: Granulocyte count less than 500/mm^3 Platelet count less than 20,000/mm^3 Reticulocyte count less than 50,000/mm^3 Following etiologies eligible: Fanconi's anemia Hypoplastic leukemia Monosomy 7 Drug exposure (chloramphenicol, NSAIDS) Viral exposure (EBV, hepatitis, parvovirus, HIV) Nutritional deficiencies Thymoma Paroxysmal nocturnal hemoglobinuria Amegakaryocytic thrombocytopenia OR Histologically confirmed myelodysplastic syndrome (MDS) that is refractory to medical management or with cytogenic abnormalities predictive of transformation into acute leukemia, including 5q-, 7q-, monosomy 7, or trisomy 8 The following etiologies only are eligible: Refractory anemia Refractory anemia with ringed sideroblasts De novo primary MDS Therapy-related secondary MDS OR Confirmed diagnosis of inherited hematopoietic disorder that is refractory to medical management Following etiologies eligible: Severe combined immunodeficiency Familial erythrophagocytic lymphohistiocytosis Wiskott-Aldrich syndrome Kostmann's syndrome (infantile histiocytosis) Chronic granulomatous disease Leukocytic 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 Lipodoses Autologous or haploidentical related peripheral blood stem cells available as backup Serologically matched umbilical cord blood unit available in the New York Blood Center's Placental Blood Project, or other acceptable umbilical cord blood registry PATIENT CHARACTERISTICS: Age: 55 and under Performance status: Zubrod 0-1 Karnofsky 80-100% Life expectancy: At least 3 months Hematopoietic: See Disease Characteristics Hepatic: ALT/AST no greater than 4 times normal Bilirubin no greater than 2.0 mg/dL Renal: Creatinine no greater than 2.0 mg/dL Creatinine clearance at least 50 mL/min Cardiovascular: Normal cardiac function by echocardiogram or radionuclide scan Shortening fraction or ejection fraction at least 80% normal for age Non-Fanconi patients with acquired or congenital cardiomyopathy may receive melphalan as a substitute for cyclophosphamide Pulmonary: FVC and FEV_1 at least 60% of predicted for age DLCO at least 60% of predicted in adult patients Other: No active concurrent malignancy No active infection Not pregnant or nursing HIV negative Must have an available serologic matched Umbilical Cord Blood Unit (UCBU) in the New York Blood Center's Placental Blood Project, or other acceptable Umbilical Cord Blood (UCB) registry 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

  • Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

Event-free survival by disease assessment

Secondary Outcome Measures

Umbilical cord blood donor engraftment by chimerism and complete blood count (CBC) at time of myeloid recovery.

Full Information

First Posted
November 1, 1999
Last Updated
June 10, 2010
Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00003336
Brief Title
Pilot Study Of Unrelated UCB Transplant for Non-Malignant Hematologic Conditions
Official Title
A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Patients With Severe Aplastic Anemia, Inborn Errors in Metabolism, or Inherited Hematologic Stem Cell Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
June 2010
Overall Recruitment Status
Completed
Study Start Date
January 1998 (undefined)
Primary Completion Date
December 2005 (Actual)
Study Completion Date
February 2006 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells. PURPOSE: This phase II trial is studying how well umbilical cord blood transplantation works in treating patients with severe aplastic anemia, malignant thymoma, or myelodysplasia.
Detailed Description
OBJECTIVES: 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. Evaluate the rate and quality of immunologic reconstitution in this patient population. OUTLINE: Patients are stratified according to weight (under 45 kg vs over 45 kg). Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT). The regimen varies according to the underlying cause of the anemia, but could include busulfan, cyclophosphamide or melphalan, anti-thymocyte globulin or methylprednisolone, and/or radiation therapy. One day after the conditioning regimen is completed, patients receive the UCBT. Patients are followed weekly for 3 months, at 6 months, then every 6 months for 2.5 years, then annually thereafter. 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
Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases
Keywords
refractory anemia, refractory anemia with ringed sideroblasts, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, atypical chronic myeloid leukemia, myelodysplastic/myeloproliferative disease, unclassifiable, childhood myelodysplastic syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
anti-thymocyte globulin
Intervention Description
The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).
Intervention Type
Drug
Intervention Name(s)
busulfan
Intervention Description
The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Description
The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Description
The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).
Intervention Type
Drug
Intervention Name(s)
methylprednisolone
Intervention Description
The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).
Intervention Type
Procedure
Intervention Name(s)
bone marrow ablation with stem cell support
Intervention Type
Procedure
Intervention Name(s)
umbilical cord blood transplantation
Intervention Description
One day after the conditioning regimen is completed, patients receive the UCBT.
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Intervention Description
The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).
Primary Outcome Measure Information:
Title
Event-free survival by disease assessment
Time Frame
at 100 days and at 6, 9, 12, 18, and 24 months
Secondary Outcome Measure Information:
Title
Umbilical cord blood donor engraftment by chimerism and complete blood count (CBC) at time of myeloid recovery.
Time Frame
100 days and at 6, 9, 12, 18, and 24 months

10. Eligibility

Sex
All
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of severe aplastic anemia based on bone marrow cellularity of less than 20% Must meet at least two of the following criteria: Granulocyte count less than 500/mm^3 Platelet count less than 20,000/mm^3 Reticulocyte count less than 50,000/mm^3 Following etiologies eligible: Fanconi's anemia Hypoplastic leukemia Monosomy 7 Drug exposure (chloramphenicol, NSAIDS) Viral exposure (EBV, hepatitis, parvovirus, HIV) Nutritional deficiencies Thymoma Paroxysmal nocturnal hemoglobinuria Amegakaryocytic thrombocytopenia OR Histologically confirmed myelodysplastic syndrome (MDS) that is refractory to medical management or with cytogenic abnormalities predictive of transformation into acute leukemia, including 5q-, 7q-, monosomy 7, or trisomy 8 The following etiologies only are eligible: Refractory anemia Refractory anemia with ringed sideroblasts De novo primary MDS Therapy-related secondary MDS OR Confirmed diagnosis of inherited hematopoietic disorder that is refractory to medical management Following etiologies eligible: Severe combined immunodeficiency Familial erythrophagocytic lymphohistiocytosis Wiskott-Aldrich syndrome Kostmann's syndrome (infantile histiocytosis) Chronic granulomatous disease Leukocytic 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 Lipodoses Autologous or haploidentical related peripheral blood stem cells available as backup Serologically matched umbilical cord blood unit available in the New York Blood Center's Placental Blood Project, or other acceptable umbilical cord blood registry PATIENT CHARACTERISTICS: Age: 55 and under Performance status: Zubrod 0-1 Karnofsky 80-100% Life expectancy: At least 3 months Hematopoietic: See Disease Characteristics Hepatic: ALT/AST no greater than 4 times normal Bilirubin no greater than 2.0 mg/dL Renal: Creatinine no greater than 2.0 mg/dL Creatinine clearance at least 50 mL/min Cardiovascular: Normal cardiac function by echocardiogram or radionuclide scan Shortening fraction or ejection fraction at least 80% normal for age Non-Fanconi patients with acquired or congenital cardiomyopathy may receive melphalan as a substitute for cyclophosphamide Pulmonary: FVC and FEV_1 at least 60% of predicted for age DLCO at least 60% of predicted in adult patients Other: No active concurrent malignancy No active infection Not pregnant or nursing HIV negative Must have an available serologic matched Umbilical Cord Blood Unit (UCBU) in the New York Blood Center's Placental Blood Project, or other acceptable Umbilical Cord Blood (UCB) registry 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
Mary J. Laughlin, MD
Organizational Affiliation
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106-7284
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
11407342
Citation
Laughlin MJ, Barker J, Bambach B, Koc ON, Rizzieri DA, Wagner JE, Gerson SL, Lazarus HM, Cairo M, Stevens CE, Rubinstein P, Kurtzberg J. Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med. 2001 Jun 14;344(24):1815-22. doi: 10.1056/NEJM200106143442402.
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Pilot Study Of Unrelated UCB Transplant for Non-Malignant Hematologic Conditions

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