Leukemia, Acute Lymphocytic (ALL)Phase 3NCT00186823

Haploidentical Stem Cell Transplantation for Patients With Hematologic Malignancies

A Phase 3 study testing Miltenyi Biotec CliniMACS, Stem Cell Transplantation and TBI, systemic chemotherapy and antibodies as follows: in people with Leukemia, Acute Lymphocytic (ALL) and Leukemia, Myeloid, Acute(AML), run by St. Jude Children's Research Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 2 to 21 years
Conditions the study is for: Leukemia, Acute Lymphocytic (ALL), Leukemia, Myeloid, Acute(AML), Leukemia, Myeloid, Chronic(CML)
What is being tested?: Miltenyi Biotec CliniMACS, Stem Cell Transplantation and TBI, systemic chemotherapy and antibodies as follows:
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: 57 participants
Where: 1 siteUnited States
Study dates: Mar 2002to Jan 2009
Phase: Phase 3

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

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.

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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

Who cannot join

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

Trial locations and contacts

1 site in 1 country.

United States1 site

St. Jude Children's Research Hospital
Memphis, Tennessee, 38105

Other trials in United States

About this study

Official title: Haploidentical Stem Cell Transplantation Utilizing Purified CD34+ Hematopoietic Cells for Patients With Hematologic Malignancies

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.

Read the 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.

Conditions: Leukemia, Acute Lymphocytic (ALL), Leukemia, Myeloid, Acute(AML), Leukemia, Myeloid, Chronic(CML), Juvenile Myelomonocytic Leukemia(JMML), Hemoglobinuria, Paroxysmal Nocturnal (PNH), Lymphoma, Non-Hodgkin (NHL)
Being tested: Miltenyi Biotec CliniMACS, Stem Cell Transplantation, TBI, systemic chemotherapy and antibodies as follows:
Keywords: Haploidentical stem cell transplant, Allogeneic stem cell transplant, Mismatched family member stem cell donor transplant, Bone marrow transplantHigh risk hematologic malignancies
Medical subject headings: Leukemia, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Juvenile, Hemoglobinuria, Hemoglobinuria, Paroxysmal, Lymphoma, Lymphoma, Non-Hodgkin, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Miltenyi Biotec CliniMACSDevice
A stem cell selection device.
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.
TBI, systemic chemotherapy and antibodies as follows:Drug
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.

Study groups in NCT00186823
Study group	Role	What they receive
1	Other	Not described Receives: Device: Miltenyi Biotec CliniMACS; Procedure: Stem Cell Transplantation; Drug: TBI, systemic chemotherapy and antibodies as follows:

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: September 2005

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2002Jan 2009

First posted16 Sep 2005 (estimated)
Study startMar 2002
Primary completionSep 2005
Study completionJan 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Leukemia, Acute Lymphocytic (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 3
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 57 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00186823
Sponsor's protocol ID: HAPSCT
Status last verified: Jan 2009
First submitted: 9 Sep 2005
Last updated: 29 Jan 2009
Results posted: No
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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