Unrelated Cord Blood Transplant Plus a Haplo-Identical (Half-Matched), T-Cell Depleted Stem Transplant From a Related Donor for Subjects With High Risk Malignancies
This study has been completed.
Miltenyi Biotec GmbH
Information provided by (Responsible Party):
Joanne Kurtzberg, Duke University Medical Center
First received: December 27, 2007
Last updated: November 28, 2012
Last verified: November 2012
Subjects will be diagnosed with a hematological malignancy (cancer of the blood), which is unlikely to be cured with conventional non-transplant therapy. The best results of bone marrow transplant are obtained with the donor is a relative that has identical tissue type (HLA-type). These subjects will not have such a donor available but they will have a appropriately matching unrelated umbilical cord blood unit. However, the cord blood unit does not contain a high enough number of cells and may take longer to engraft (or grow). The purpose of this study is to determine whether the addition of stem cells from a family member to supplement a standard unrelated cord blood transplant is safe and will increase the success of the cord blood transplantation procedure. Subjects enrolled in this study will receive an unrelated cord blood transplant plus a haplo-identical (half-matched), T-cell depleted stem transplant from a related donor. The goal of this study is to determine whether the addition of the related stem cells accelerates bone marrow recovery and improves long-term disease free survival.
Biological: haplo/cord transplant
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Prospective, Phase I/II Trial Determining the Efficacy and Safety of Allogeneic Hematopoietic Stem Cell Transplantation Using Banked Unrelated Umbilical Cord Blood Supplemented With Related, Haplo-Identical T-Cell Depleted Stem Cells in Subjects With High Risk Malignancies
Primary Outcome Measures:
- The primary endpoint of the study is number of days to ANC of 500/uL [ Time Frame: By day 100 ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- 180 day survival [ Time Frame: 180 days ] [ Designated as safety issue: No ]
- Non-relapse mortality in the first 180 days post transplant [ Time Frame: 180 days ] [ Designated as safety issue: No ]
- Number of days to untransfused platelet count of 50K/uL [ Time Frame: Approximately 1 year ] [ Designated as safety issue: No ]
- Incidence of primary and secondary graft failure [ Time Frame: 100 days post transplant ] [ Designated as safety issue: No ]
- Incidence and severity of acute and chronic graft-versus-host disease (GVHD) [ Time Frame: acute- through 100 days, chronic- indefinitely ] [ Designated as safety issue: No ]
- Pace and quality of immune reconstitution [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Rates of leukemic relapse [ Time Frame: 1 year and beyond ] [ Designated as safety issue: No ]
- Donor chimerism [ Time Frame: Measured around day 28, 42, 60, 100, 180, 270, 360 and yearly (at minimum) ] [ Designated as safety issue: No ]
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||April 2012 (Final data collection date for primary outcome measure)
single arm study
Biological: haplo/cord transplant
T-cell depleted haplo-matched cells from related donor and unrelated umbilical cord blood
|Ages Eligible for Study:
||up to 55 Years
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Patient Selection Criteria: Patients with high risk or refractory malignancies, myelodysplasia or severe aplastic anemia amenable to stem cell transplantation therapy but lacking conventional related or unrelated donors will be eligible for this trial.
- Have a consenting related haplo-identical (3/6 or 4/6) stem cell donor;
- Have an available 3, 4, 5, or 6/6 antigen matching unrelated UCB unit that will deliver a cell dose between 2.0-5.0 x 10e7cells/kg.
- Not have a consenting 6/6 or 5/6 antigen matched related bone marrow donor or genetically matched unrelated BM or adult stem cell donor.
- Patients must be <55 years of age at the time of study enrollment.
- Patients must have histologically confirmed diagnosis of a hematologic malignancy, MDS or severe aplastic anemia. Eligible patients include the following:
- Patients with high risk ALL in first complete remission, with high risk being defined by the presence of hypodiploidy, t(4;11; MLL. 11q23) or t(9;22), or patients presenting with extreme hyperleukocytosis (initial WBC >500,000/ml) or failure to achieve a complete remission after standard induction therapy.
- All patients with ALL or ANLL in second or subsequent remission.
- Patients with ALL or ANLL in relapse.
- Patients with MDS.
- Patients with CML in any chronic phase, accelerated phase or blast crisis.
- Patients with severe aplastic anemia refractory to medical therapy.
- Patients must not have active CNS disease at the time of study enrollment.
- Patients must have a good performance status (Lansky 80-100%, Karnofsky 50-100%).
- Patients must have adequate function of other organ systems as measured by:
- Creatinine < 2.0 mg/dl and creatinine clearance > 50 cc/min/m2.
- Hepatic transaminases (ALT/AST) < 4 x normal, bilirubin < 2.0 mg/dl.
- Normal cardiac function by echocardiogram or radionuclide scan, (ejection fraction or shortening fraction > 80% of normal value for age).
- Pulmonary function tests demonstrating FVC and FEV1 of >60% of predicted for age. For adult patients DLCO > 60% of predicted. If patient cannot perform PFTs, clearance by the pediatric or adult pulmonologist will be required.
- Patients must not have uncontrolled infections at the time of cytoreduction.
- Patient, parent, or legal guardian must have given written informed consent according to FDA guidelines.
- Patients may not be pregnant or lactating and must have a current negative pregnancy test.
- Patients must have a minimum life expectancy of at least 3 months.
- Patients must have an available related haplo-identical stem cell donor and an available unrelated cord blood donor delivering between 2 x10e7 cells/kg and 5 x 10e7 cells/kg and matching at a minimum of 3/6 HLA loci.
- Patients must be HIV negative.
- Patients must not be concurrently involved in any other clinical trial that affects engraftment or immune reconstitution (e.g. other hematopoietic growth factors).
- Patients must not have any co-morbid condition which, in the view of the Principal Investigators, renders the patient at too high a risk from treatment complications and regimen related morbidity/mortality.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00673114
|Duke University Medical Center Pediatric Blood and Marrow Transplant
|Durham, North Carolina, United States, 27705 |
Miltenyi Biotec GmbH
||Joanne Kurtzberg, MD
||Duke University Medical Center Pediatric Blood and Marrow Transplant
No publications provided
||Joanne Kurtzberg, Professor of Pediatrics, Duke University Medical Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||December 27, 2007
||November 28, 2012
||United States: Food and Drug Administration
Keywords provided by Duke University:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on December 05, 2013
Bone Marrow Diseases
Neoplasms by Site