Haploidentical Hematopoietic Stem Cell Transplantation
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02165007|
Recruitment Status : Active, not recruiting
First Posted : June 17, 2014
Last Update Posted : August 31, 2022
- Study Details
- Tabular View
- No Results Posted
- How to Read a Study Record
|Condition or disease||Intervention/treatment||Phase|
|Sickle Cell-thalassemia Disease Thalassemia||Drug: peripheral blood stem cell graft that are CD34+ selected||Phase 1|
Research subjects will undergo reduced intensity conditioning (Hydroxyurea, ATG, Fludarabine, Thiotepa, Melphalan) followed by infusion of a peripheral blood stem cell graft collected from haploidentical family donors that are CD34+ positively selected using the CliniMACS device. Sirolimus will be used for GVHD prophylaxis and given for 9 months post-transplant and then tapered off by one year
The use of the CliniMACS device for CD34 selection will be performed at CNMC through cross-reference of the master file for CliniMACS CD34+ Reagent by Milteyni Biotech (BB-MF 8061).
CliniMACs is an electromechanical device intended to isolate certain cell subsets from mixed cell populations. When used in combination with the CliniMACs CD34 reagent, it is possible to prepare extremely pure populations of CD34+ cells with upwards of 5 logs depletion of contaminating T cells within a closed and sterile system.
We intend to use this system to select cells from HLA haploidentical related donors who have been mobilized with G-CSF prior to stem cell collection. Since previous investigations of this strategy in adult patients have not translated into enhanced long term survival, we intend to limit this protocol to patients under the age of 22 as they have more rapid immune reconstitution.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR CHILDREN WITH SICKLE CELL DISEASE AND THALASSEMIA USING CD34+ POSITIVE SELECTED GRAFTS|
|Study Start Date :||January 2015|
|Estimated Primary Completion Date :||July 2023|
|Estimated Study Completion Date :||November 2023|
Experimental: peripheral blood stem cell graft that are CD34+ selected
peripheral blood stem cell graft that are CD34+ selected. All patients will undergo reduced intensity conditioning regimen which followed by infusion of a peripheral blood stem cell graft collected from haploidentical family donors that are CD34+ positively selected using the CliniMACS device and Sirolimus will be used for GVHD prophylaxis and given for 9 months post-transplant and then tapered off by one year (see intervention).
Drug: peripheral blood stem cell graft that are CD34+ selected
The preparatory regimen will consist of Hydroxyurea from Days -50 to -22, Alemtuzumab from days -21 to -19 (test dose Alemtuzumab on day -22), Fludarabine days -8 to -4, Thiotepa Day -4, Melphalan day -3 to -2 (Table 4a). In patients with intolerance to or have received alemtuzumab in the prior 6 months, alemtuzumab will be replaced with rabbit ATG on days -10 through -7, followed by infusion of a peripheral blood stem cell graft collected from haploidentical family donors that are CD34+ positively selected using the CliniMACS device. Sirolimus will be used for GVHD prophylaxis and given for 9 months post-transplant and then tapered off by one year.
- Incidence of transplant related adverse outcomes [ Time Frame: 60 days ]
The primary endpoint of this trial is safety. Transplant related adverse outcomes and non-hematological toxicity will be measured through Day +60 on this objective to include:
- Non-hematological severe (Grade IV and V) organ specific toxicity according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0)
- Rates of non-engraftment
- Severe acute (Grade III-IV)
- Veno-occlusive disease of the liver
- Idiopathic pneumonia syndrome
- Seizures/Posterior reversible encephalopathy syndrome (PRES)
- Overall survival [ Time Frame: 2 years ]Overall survival upto 2 years
- Graft failure [ Time Frame: 2 years ]Graft failure upto 2 years
- Grades II-IV and III-IV acute GVHD [ Time Frame: 180 days ]Grades II-IV and III-IV acute GVHD at day +180
- Chronic GVHD [ Time Frame: 1 year ]Chronic GVHD by 1 yea
- Transplant-related mortality [ Time Frame: 100 days ]Transplant-related mortality at Day+ 100
- Viral infection rates [ Time Frame: 6 months ]Viral infection rates at 6 months: Reactivation of CMV, Adenovirus and EBV detected on peripheral blood monitoring or any visceral disease with documented molecular studies for these viruses within the first six months post transplantation will be recorded
- Lymphocyte reconstitution [ Time Frame: 1 year ]Lymphocyte reconstitution upto 1 year post transplant
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||up to 22 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- First allogeneic transplant
- Age up to 22 years
- Patients with severe sickle cell disease (stroke, elevated TCD velocities, >2 acute chest syndrome, ongoing chronic red cell transfusion > 6 months)
- Patients with transfusion dependent thalassemia and evidence of iron overload
- Patients must have a related donor that is HLA-matched at >/=4 of 8 but <8/8 HLA-A, -B, -C and -DRB1
- Cardiac function: Shortening fraction >25%; ejection fraction >40%
- Estimated creatinine clearance greater than 50 mL/minute
- Pulmonary function: DLCO ≥40% (adjusted for hemoglobin) and FEV1≥50% in patients 7 years and older with normal cognitive function and able to perform the test adequately. If not able to complete the testing a CT chest will be required., oxygen saturation>91%
- Liver function: direct (conjugated) bilirubin < 2x the upper limit of normal and ALT/AST < 2.5x the upper normal limit.
- Signed informed consent.
- Life expectancy less than 6 months
- Patients with uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning. Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning.
- Pregnant or breastfeeding patients
- Patients seropositive for the human immunodeficiency virus (HIV)
- Patient with active Hepatitis B or C determined by serology and/or NAAT
- Active hepatitis, bridging fibrosis or cirrhosis on liver biopsy (biopsy required for patients on chronic transfusion therapy for > 1 year and evidence of iron overload with ferritin >1000 ng/mL)
- Patients with suitable 8/8 HLA matched related and unrelated donors
- Patients who have an intolerance to or have received alemtuzumab in the prior 6 months will be excluded from enrollment unless alemtuzumab is replaced with rabbit ATG in the conditioning regimen
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02165007
|United States, District of Columbia|
|Childrens National Medical Center|
|Washington, District of Columbia, United States, 20010|
|Responsible Party:||Catherine Bollard, Director- Center for Cancer and Immunology Research, Children's National Research Institute|
|Other Study ID Numbers:||
|First Posted:||June 17, 2014 Key Record Dates|
|Last Update Posted:||August 31, 2022|
|Last Verified:||August 2022|
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Physiological Effects of Drugs