search
Back to results

Haploidentical Stem Cell Transplantation for Patients With Hematologic Malignancies

Primary Purpose

Leukemia, Acute Lymphocytic (ALL), Leukemia, Myeloid, Acute(AML), Leukemia, Myeloid, Chronic(CML)

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Miltenyi Biotec CliniMACS
Stem Cell Transplantation
TBI, systemic chemotherapy and antibodies as follows:
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 Leukemia, Acute Lymphocytic (ALL) focused on measuring Haploidentical stem cell transplant, Allogeneic stem cell transplant, Mismatched family member stem cell donor transplant, Bone marrow transplantHigh risk hematologic malignancies

Eligibility Criteria

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

Inclusion Criteria: Lacking a HLA-identical sibling or unrelated donor matched at 6 HLA loci formally requested within an approximate 90 day period from search initiation and who has a mismatched family member donor available At least 2 and less than or equal to 21 years of age Must have one of the following diagnosis: Acute lymphoid leukemia (ALL) in second, third, or subsequent remission. ALL in first remission but high risk for relapse. Acute myeloid leukemia (AML) in relapse or remission. Secondary AML / MDS Chronic myeloid leukemia (CML) Juvenile myelomonocytic leukemia (JMML). Myelodysplastic syndrome (MDS). Paroxysmal nocturnal hemoglobinuria (PNH) Non-Hodgkin lymphoma in second or subsequent CR Patients with a shortening fraction ≥ 25% Patients with a creatinine clearance ≥ 40cc/min/1.73m^2 Patients with FVC ≥ 40% of predicted or pulse oximetry ≥ 92% on room air Patients with direct bilirubin ≤ 3 mg/dL or SGPT ≤ 500 U/L Patients with a Karnofsky or Lansky (age dependent) performance score of ≥ 70 Mismatched family member donor is available, HIV negative and ≥ 18 years of age Exclusion Criteria: Patients who have received a previous hematopoietic stem cell allograft Patients with a known allergy to rabbit or murine products Patients with isolated CNS, testicular or other isolated extramedullary site of relapse

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 describe rate of hematopoietic and immune reconstitution in first 100 days posttransplant for pediatric patients with high-risk hematologic malignancies receiving haploidentical transplant processed with investigational CliniMACS cell sorting device.

Secondary Outcome Measures

Full Information

First Posted
September 9, 2005
Last Updated
January 28, 2009
Sponsor
St. Jude Children's Research Hospital
search

1. Study Identification

Unique Protocol Identification Number
NCT00186823
Brief Title
Haploidentical Stem Cell Transplantation for Patients With Hematologic Malignancies
Official Title
Haploidentical Stem Cell Transplantation Utilizing Purified CD34+ Hematopoietic Cells for Patients With Hematologic Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
January 2009
Overall Recruitment Status
Completed
Study Start Date
March 2002 (undefined)
Primary Completion Date
September 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
Blood and marrow stem cell transplant has improved the outcome for patients with high-risk hematologic malignancies. However, most patients do not have an appropriate HLA (immune type) matched sibling donor available and/or are unable to identify an acceptable unrelated HLA matched donor through the registries in a timely manner. Another option is haploidentical transplant using a partially matched family member donor. Although haploidentical transplant has proven curative in many patients, this procedure has been hindered by significant complications, primarily regimen-related toxicity including graft versus host disease (GVHD) and infection due to delayed immune reconstitution. These can, in part, be due to certain white blood cells in the graft called T cells. GVHD happens when the donor T cells recognize the body tissues of the patient (the host) are different and attack these cells. Although too many T cells increase the possibility of GVHD, too few may cause the recipient's immune system to reconstitute slowly or the graft to fail to grow, leaving the patient at high-risk for significant infection. This research project will investigate the use of particular pre-transplant conditioning regimen (chemotherapy, antibodies and total body irradiation) followed by a stem cell infusion from a "mismatched" family member donor. Once these stem cells are obtained they will be highly purified in an effort to remove T cells using the investigational CliniMACS stem cell selection device. The primary goal of this study will be to determine the rate of neutrophil and platelet engraftment, as well as the degree and rate of immune reconstitution in the first 100 days posttransplant for patients who receive this study treatment. Researchers will also study ways to decrease complications that may occur with a transplant from a genetically mismatched family donor.
Detailed Description
Secondary outcome evaluations for this clinical study include the following: To estimate overall survival, disease free survival and event free survival for these patients To estimate the incidence of grade 2 to 4 acute GvHD in these patients To estimate the incidence of chronic GvHD and graft failure in these patients To estimate the incidence of non-hematologic peri-transplant regimen-related toxicity and regimen-related mortality in the first 100 days after transplantation in these patients To estimate the number of patients who require donor lymphocyte infusions and/or stem cell boosts after transplantation in this group of patients and evaluate its impact on immune reconstitution and engraftment To estimate the number of patients who develop evidence of EBV reactivation or post transplant lymphoproliferative disease (PTLPD) post transplant in this group of patients Describe the pharmacokinetics of rabbit anti-thymocyte globulin (rATG) in patients receiving allogeneic transplantation and determine the frequency of rATG antibody development Explore dose and patient characteristics as determinants of active rATG pharmacokinetic parameters Originally this study began as a randomized comparison of two methods of stem cell selection utilizing the CliniMACS device. Both arms provided a purified product of CD34+ hematopoietic cells that was depleted of T-lymphocytes. One arm utilized a positive selection methodology using an anti-CD34 antibody and the other arm utilized negative selection with the anti-CD3 antibody OKT-3. There were no toxicities noted that would have required the study to be interrupted early, however, due to low accrual, it was decided to redesign the study. The new design focused on the standard arm utilizing negative selection, and all subsequent participants were treated in that manner. The patients who were treated on the positive selection arm are continuing to be monitored as specified in the original protocol, but will be reported in a descriptive manner only. The primary and secondary objectives of the current version of this study will be answered only by those patients receiving a haploidentical stem cell transplant utilizing a negative selection methodology.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Acute Lymphocytic (ALL), Leukemia, Myeloid, Acute(AML), Leukemia, Myeloid, Chronic(CML), Juvenile Myelomonocytic Leukemia(JMML), Hemoglobinuria, Paroxysmal Nocturnal (PNH), Lymphoma, Non-Hodgkin (NHL), Myelodysplastic Syndrome (MDS)
Keywords
Haploidentical stem cell transplant, Allogeneic stem cell transplant, Mismatched family member stem cell donor transplant, Bone marrow transplantHigh risk hematologic malignancies

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Other
Intervention Type
Device
Intervention Name(s)
Miltenyi Biotec CliniMACS
Intervention Description
A stem cell selection device.
Intervention Type
Procedure
Intervention Name(s)
Stem Cell Transplantation
Intervention Description
An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device.
Intervention Type
Drug
Intervention Name(s)
TBI, systemic chemotherapy and antibodies as follows:
Intervention Description
Transplant recipients received a myeloablative conditioning regimen consisting of total body irradiation, thiotepa, cyclophosphamide, ATG, and OKT3. Rituximab was provided prior to transplant for PTLPD prophylaxis. In addition to T cell depletion of the donor product, cyclosporine was administered for GVHD prophylaxis.
Primary Outcome Measure Information:
Title
To describe rate of hematopoietic and immune reconstitution in first 100 days posttransplant for pediatric patients with high-risk hematologic malignancies receiving haploidentical transplant processed with investigational CliniMACS cell sorting device.
Time Frame
September 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: Lacking a HLA-identical sibling or unrelated donor matched at 6 HLA loci formally requested within an approximate 90 day period from search initiation and who has a mismatched family member donor available At least 2 and less than or equal to 21 years of age Must have one of the following diagnosis: Acute lymphoid leukemia (ALL) in second, third, or subsequent remission. ALL in first remission but high risk for relapse. Acute myeloid leukemia (AML) in relapse or remission. Secondary AML / MDS Chronic myeloid leukemia (CML) Juvenile myelomonocytic leukemia (JMML). Myelodysplastic syndrome (MDS). Paroxysmal nocturnal hemoglobinuria (PNH) Non-Hodgkin lymphoma in second or subsequent CR Patients with a shortening fraction ≥ 25% Patients with a creatinine clearance ≥ 40cc/min/1.73m^2 Patients with FVC ≥ 40% of predicted or pulse oximetry ≥ 92% on room air Patients with direct bilirubin ≤ 3 mg/dL or SGPT ≤ 500 U/L Patients with a Karnofsky or Lansky (age dependent) performance score of ≥ 70 Mismatched family member donor is available, HIV negative and ≥ 18 years of age Exclusion Criteria: Patients who have received a previous hematopoietic stem cell allograft Patients with a known allergy to rabbit or murine products Patients with isolated CNS, testicular or other isolated extramedullary site of relapse
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gregory A. 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

Learn more about this trial

Haploidentical Stem Cell Transplantation for Patients With Hematologic Malignancies

We'll reach out to this number within 24 hrs