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Stem Cell Transplantation for Patients With Hematologic Malignancies

Primary Purpose

Acute Lymphoblastic Leukemias, Acute Myelocytic Leukemia, Chronic Myeloid Leukemia

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Allogeneic Stem Cell Transplantation
Chemotherapy and antibodies
Sponsored by
St. Jude Children's Research Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemias focused on measuring High risk hematologic malignancies, Allogeneic stem cell transplant, Matched unrelated donor transplantation, Unmanipulated stem cell graft, Bone marrow transplantation

Eligibility Criteria

2 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: All patients lacking an HLA identical sibling for whom an unrelated donor matched at 6/6 HLA loci is formally requested within about 3 months of search initiation Age greater than or equal to 24 months, but less than 21 years for new patients. Diagnosis of one of the following high risk hematological malignancies: Acute lymphoblastic leukemia (in second or subsequent remission or high risk in first remission) Acute myeloid leukemia (in relapse or remission) Secondary AML/MDS Chronic myeloid leukemia Juvenile myelomonocytic leukemia Myelodysplastic syndrome Paroxysmal nocturnal hemoglobinuria Non-Hodgkin's lymphoma (in second or subsequent remission) Exclusion Criteria: Patients with symptomatic cardiac disease, or evidence of significant cardiac disease by echocardiogram, or cardiac shortening fraction below 25% Patients with renal creatinine clearance < 40ml/min/1.73m^2 Patients with FVC < 40% predicted or pulse oximetry less than or equal to 92% on room air if unable to perform pulmonary function tests Patients with direct bilirubin > 3 mg/dl Patients with SGPT > 500 U/L Patients with a Karnofsky or Lansky performance score < 70 Patients who have received a previous allogeneic stem cell transplant Patients with a known allergy to rabbit or murine products Patients with isolated extramedullary leukemic relapse, including isolated CNS or testicular recurrence

Sites / Locations

  • St. Jude Children's Research Hospital

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

1

Arm Description

Outcomes

Primary Outcome Measures

To estimate the occurrence of acute graft versus host disease in patients who have received an unmanipulated hematopoietic stem cell transplant from a matched unrelated donor

Secondary Outcome Measures

Full Information

First Posted
September 8, 2005
Last Updated
January 28, 2009
Sponsor
St. Jude Children's Research Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT00152139
Brief Title
Stem Cell Transplantation for Patients With Hematologic Malignancies
Official Title
Hematopoietic Stem Cell Transplantation Using Matched Unrelated Donor Peripheral Blood or Bone Marrow for Patients With Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
January 2009
Overall Recruitment Status
Completed
Study Start Date
May 2002 (undefined)
Primary Completion Date
June 2005 (Actual)
Study Completion Date
January 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
St. Jude Children's Research Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemias, Acute Myelocytic Leukemia, Chronic Myeloid Leukemia, Juvenile Myelomonocytic Leukemia, Myelodysplastic Syndrome, Hemoglobinuria, Paroxysmal, Non-Hodgkin Lymphoma
Keywords
High risk hematologic malignancies, Allogeneic stem cell transplant, Matched unrelated donor transplantation, Unmanipulated stem cell graft, Bone marrow transplantation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
33 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Other
Intervention Type
Procedure
Intervention Name(s)
Allogeneic Stem Cell Transplantation
Other Intervention Name(s)
Allogeneic stem cell transplant, Matched unrelated donor stem cell transplant, Bone marrow stem cell transplant
Intervention Description
An infusion of HLA matched unrelated bone marrow or peripheral blood stem cells.
Intervention Type
Drug
Intervention Name(s)
Chemotherapy and antibodies
Other Intervention Name(s)
Graft versus host disease
Intervention Description
Participants received a standard conditioning regimen consisting of total body irradiation, cyclophosphamide, thiotepa and ATG. GVHD prophylaxis consisted of cyclosporine and Methotrexate.
Primary Outcome Measure Information:
Title
To estimate the occurrence of acute graft versus host disease in patients who have received an unmanipulated hematopoietic stem cell transplant from a matched unrelated donor
Time Frame
July 2005

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All patients lacking an HLA identical sibling for whom an unrelated donor matched at 6/6 HLA loci is formally requested within about 3 months of search initiation Age greater than or equal to 24 months, but less than 21 years for new patients. Diagnosis of one of the following high risk hematological malignancies: Acute lymphoblastic leukemia (in second or subsequent remission or high risk in first remission) Acute myeloid leukemia (in relapse or remission) Secondary AML/MDS Chronic myeloid leukemia Juvenile myelomonocytic leukemia Myelodysplastic syndrome Paroxysmal nocturnal hemoglobinuria Non-Hodgkin's lymphoma (in second or subsequent remission) Exclusion Criteria: Patients with symptomatic cardiac disease, or evidence of significant cardiac disease by echocardiogram, or cardiac shortening fraction below 25% Patients with renal creatinine clearance < 40ml/min/1.73m^2 Patients with FVC < 40% predicted or pulse oximetry less than or equal to 92% on room air if unable to perform pulmonary function tests Patients with direct bilirubin > 3 mg/dl Patients with SGPT > 500 U/L Patients with a Karnofsky or Lansky performance score < 70 Patients who have received a previous allogeneic stem cell transplant Patients with a known allergy to rabbit or murine products Patients with isolated extramedullary leukemic relapse, including isolated CNS or testicular recurrence
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory Hale, M.D.
Organizational Affiliation
St. Jude Children's Research Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Jude Children's Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.stjude.org
Description
St. Jude Children's Research Hospital

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Stem Cell Transplantation for Patients With Hematologic Malignancies

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