Trial Of Double Umbilical Cord Blood Transplantation
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|ClinicalTrials.gov Identifier: NCT00763490|
Recruitment Status : Completed
First Posted : October 1, 2008
Results First Posted : January 12, 2015
Last Update Posted : December 23, 2016
This pilot research study is to investigate the safety and effectiveness of stem cell transplantation to treat blood-related (hematopoietic) cancers, using stem cells collected from two different, umbilical cord blood donors. Subjects in this study are receiving a stem cell transplant because other treatments have failed or their disease is unlikely to respond to other treatment options.
Blood-related cancers can be treated and sometimes cured with very high doses of chemotherapy and radiation therapy, given to kill the cancer cells; however, these treatments can prove unsuccessful and can harm normal cells in the bone marrow or a patient's disease may be unlikely to respond to these treatment options.
Hematopoietic stem cells transplantation (HSCT) is a potential cure, but opportunities to perform HSCT are limited by donor availability. Only 20-30% of patients may have matched family donors. In some cases, a mismatched family donor may be suitable. For patients needing a transplant who do not have a suitably matched family donor, blood stem cells from matched unrelated donors can be used. The length of time required to identify a matched unrelated donor presents another obstacle for patients waiting to receive an HSCT.
Blood stem cells are found in umbilical cord blood (UCB), which is blood left over in the placenta (afterbirth) after a baby is born. Usually this blood is discarded with the placenta, but over the past 15 years, we have learned how to collect and freeze cord blood cells to be used for transplants at a later time. A cord blood unit is the cord blood cells collected and stored from a single placenta. More than 6,500 umbilical cord blood stem cell transplants have been done worldwide, mostly in children with leukemia. One important factor affecting the success of a cord blood transplant is the cell dose (number of stem cells in the cord blood unit / recipient's weight). Patients who receive a high cell dose (> 2.5 x 107 cells/kilogram) have better marrow recovery and a higher rate of survival than those who receive a lower cell dose.
In an attempt to make UCB transplantation possible for bigger children, adolescents and adults, researchers have tried giving two cord blood units on the same day for their transplant, one after the other. The data from more than 150 "double cord blood" transplants in adults suggest that the "double cord blood" transplants may allow bone marrow recovery and survival in patients who do not have a single cord blood unit with enough cells for successful transplantation.
This is a pilot study to research the safety and effectiveness of using two UCB units in adult and pediatric UCB transplantation when combined with a conditioning regimen called Flu/Bu4/TLI (consisting of fludarabine, busulfan and total lymphoid irradiation).
|Condition or disease||Intervention/treatment||Phase|
|Hematological Malignancies||Procedure: Full intensity, double umbilical cord, stem cell transplant Drug: Flu/Bu4 conditioning regimen Radiation: Total Lymphoid Irradiation (TLI) Drug: Graft versus Host Disease prevention (GVHD prophylaxis) Drug: Mycophenolate Mofetil||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Trial Of Double Umbilical Cord Blood Transplantation|
|Study Start Date :||December 2008|
|Actual Primary Completion Date :||March 2013|
|Actual Study Completion Date :||October 2015|
Experimental: Double cord blood transplant
'full intensity, double umbilical cord, stem cell transplant' with 'Flu/Bu4 conditioning regimen'
Procedure: Full intensity, double umbilical cord, stem cell transplant
stem cell transplant using two umbilical cord blood units, combined with a Flu/Bu4 conditioning regimen prior to transplantation
Drug: Flu/Bu4 conditioning regimen
Fludarabine: 40 mg/m² daily on days -5, -4, -3, -2
Busulfan: 3.2 mg/kg IV daily on days -5, -4, -3, -2
Radiation: Total Lymphoid Irradiation (TLI)
one dose, 400 cGy,on day -1 or day 0, prior to cord blood infusion
Drug: Graft versus Host Disease prevention (GVHD prophylaxis)
Tacrolimus for GVHD (Graft Versus Host Disease Prevention) Tacrolimus - will begin on day -3 (IV or oral) for at least 180 days. Target trough level for tacrolimus is 8-12 ng/ml. In the absence of GVHD, tacrolimus tapering will begin on day +56 post transplant.
Drug: Mycophenolate Mofetil
Mycophenolate Mofetil (MMF) for GVHD prophylaxis. MMF - will be given at a dose of 10mg/kg IV q 8 hours if the patient weight is more than 50 kg, or 15 mg/kg IV q 8 hours if less than 50 kg, beginning the morning of day -3. (If renal failure and Glomerular Filtration Rate (GFR) < 25 mL/min, the dose should not exceed 1 gm every 8 hours. (No dose adjustment for liver disease is required.) MMF should be given via IV until oral medications are tolerated.
MMF will be stopped at Day +28 if no acute GVHD is seen by that time. If there is not any donor cell engraftment, MMF will be continued as directed by the attending physician. If the patient has active acute GVHD requiring systemic therapy, MMF may be continued.
- Percentage of Participants Alive at 1 Year After Transplant [ Time Frame: 1 year ]One-year survival rate after transplant
- Percentage of Patients Alive at the End of the Trial [ Time Frame: 5 Years ]Event Free Survival (EFS) was determined. Patients were followed up to 5 years (median time of 2.35 years).
- Cumulative Incidence of Neutrophil and Platelet Engraftment [ Time Frame: Day 35 ]The failure to achieve a neutrophil count > 500/uL or a platelet count >30.0 x 10e9 /L within 35 days of the stem cell infusion will be defined as primary engraftment failure.
- Incidence of Acute (Grade II-IV) and Chronic Graft-vs-host Disease(GVHD) [ Time Frame: Up to 5 years ]
The percentage of patients with acute GVHD (Grade II-IV) was determined at 100 days. Patients were followed up to 5 years and the percentage of patients that developed chronic GVHD at the end of the study was tabulated.
Acute GVHD is staged and graded (grade 0-IV, where grade 0 is no involvement and involvement increases by grade) by the number and extent of organ involvement. Patients can have involvement of three organs: skin (rash/dermatitis), liver (hepatitis/jaundice), and gastrointestinal tract (abdominal pain/diarrhea).
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): NCT00763490
|United States, Michigan|
|University of Michigan Cancer Center|
|Ann Arbor, Michigan, United States, 48109|
|Principal Investigator:||Daniel M Couriel, MD||University of Michigan Rogel Cancer Center|