Acute Lymphoblastic Leukemia (ALL)Phase 2NCT00145613
Haploidentical Stem Cell Transplant for Treatment Refractory Hematological Malignancies
A Phase 2 study testing Stem Cell Transplantation, Miltenyi Biotec CliniMACS and Systemic chemotherapy and antibodies in people with Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML), run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
Relapsed disease is the most common cause of death in children with hematological malignancies. Patients who fail high-intensity conventional chemotherapeutic regimens or relapse after stem cell transplantation have a poor prognosis. Read more about this study
- Who is it for?
- Ages 2 to 21 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Secondary AML
- What is being tested?
- Stem Cell Transplantation, Miltenyi Biotec CliniMACS and Systemic chemotherapy and antibodies
- Type of treatment
- Injection or infusion, Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2003to Feb 2009
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
None listed.
Who cannot join
- Patients with a known allergy to murine products
- (Female Patients) Patient is pregnant
- Female Patients) Patient is lactating
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
Official title: Haploidentical Stem Cell Transplantation Utilizing T-Cell Depletion as Therapy for Patients With Refractory Hematological Malignancies
Relapsed disease is the most common cause of death in children with hematological malignancies. Patients who fail high-intensity conventional chemotherapeutic regimens or relapse after stem cell transplantation have a poor prognosis. Toxicity from multiple therapies and elevated leukemic/tumor burden usually make these patients ineligible for the aggressive chemotherapy regimens required for conventional stem cell transplantation. Alternative options are needed. One type of treatment being explored is called haploidentical transplant.
Conventional blood or bone marrow stem cell transplant involves destroying the patient's diseased marrow with radiation or chemotherapy. Healthy marrow from a donor is then infused into the patient where it migrates to the bone marrow space to begin generating new blood cells. The best type of donor is a sibling or unrelated donor with an identical immune system (HLA "match"). However, most patients do not have a matched sibling available and/or are unable to identify an acceptable unrelated donor through the registries in a timely manner. In addition, the aggressive treatment required to prepare the body for these types of transplants can be too toxic for these highly pretreated patients. Therefore doctors are investigating haploidentical transplant using stem cells from HLA partially matched family member donors.
Read more
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 patient's (the host) body tissues 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 infection. However, the presence of T cells in the graft may offer a positive effect called graft versus malignancy or GVM. With GVM, the donor T cells recognize the patient's malignant cells as diseased and, in turn, attack these diseased cells.
For these reasons, a primary focus for researchers is to engineer the graft to provide a T cell depleted product to reduce the risk of GVHD, yet provide a sufficient number of cells to facilitate immune reconstitution, graft integrity and GVM.
In this study, patients were given a haploidentical graft engineered to with specific T cell parameter values using the CliniMACS system. A reduced intensity, preparative regimen was used to reduce regimen-related toxicity and mortality. The primary goal of this study is to evaluate overall survival in those who receive this study treatment.
Read the detailed description
Secondary objectives for this protocol are to 1) assess the kinetics of lymphohematopoietic reconstitution and 2) describe the short and long-term (up to 5 years post- transplant) toxicity of haploidentical stem cell transplantation, including GVHD, in children with refractory hematological malignancies.
- Conditions
- Acute Lymphoblastic Leukemia (ALL), Acute Myeloid Leukemia (AML), Secondary AML, Myelodysplastic Syndrome (MDS), Secondary MDS, Chronic Myeloid Leukemia
- Being tested
- Stem Cell Transplantation, Miltenyi Biotec CliniMACS, Systemic chemotherapy and antibodies
- Keywords
- Haploidentical stem cell transplant, High risk hematologic malignancies, Allogeneic stem cell transplant, Mismatched family member stem cell donor
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myelomonocytic, Juvenile, Hemoglobinuria, Paroxysmal, Lymphoma, Non-Hodgkin, Hodgkin Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stem Cell TransplantationProcedure or surgery
An infusion of HLA mismatched family member donor stem cells processed through the use of the investigational Miltenyi Biotec CliniMACS device.
Miltenyi Biotec CliniMACSDevice
stem cell selection device
Systemic chemotherapy and antibodiesDrug
Also called Allogeneic stem cell transplant,, Mismatched family member donor stem cell transplant, Haploidentical donor stem cell transplant,, Reduced intensity conditioning regimen,
Transplant recipients received a non-TBI based reduced intensity conditioning regimen consisting of OKT-3, Fludarabine Thiotepa, and Melphalan. Rituximab was administered within 24 hours of the transplant in an effort to prevent PTLPD. In addition to T-cell depletion of the haploidentical stem cell product, Mycophenolate mofetil was provided as prophylaxis for GVHD.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Other | Not described Receives: Procedure: Stem Cell Transplantation; Device: Miltenyi Biotec CliniMACS; Drug: Systemic chemotherapy and antibodies |
What is being measured
The primary outcome is the main question the study is designed to answer.
To ask in terms of one-year survival the efficacy of haploidentical stem cell transplantation in children with refractory hematological malignancies.
Measured: July 2006
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2005 (estimated)
- Study startJun 2003
- Primary completionJul 2006
- Study completionFeb 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic Leukemia (ALL)Studies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Gregory Hale, M.D., Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00145613
- Sponsor's protocol ID
- REFSCT
- Status last verified
- Feb 2009
- First submitted
- 1 Sep 2005
- Last updated
- 13 Feb 2009
- Results posted
- No
- Data monitoring committee
- No