An interventional study of Busulfan and Cytoxan in Congenital Pediatric Disorders, sponsored by Baylor College of Medicine. Completed at 1 site in United States. Open to participants aged Up to 17 Years. Per ClinicalTrials.gov, last updated 2023-10-30.
Sponsored by Baylor College of Medicine · Not applicable, Interventional, and Treatment
The purpose of this study is to determine the safety and effectiveness of Umbilical Cord Blood Transplant (UCBT) to treat the patient's disease, and to see if this treatment can decrease the incidence of GVHD.
This study is for patients that were born with a disease that affects their body's metabolism or immune system. The doctor plans to treat the patient for this illness with a stem cell transplant.
While improved medical care has allowed many people with these diseases to live longer, the only way to truly cure the diseases is by means of a stem cell transplant from a donor who does not have the disease. A stem cell transplant will replace sick cells with new healthy donor cells. Stem cells grow into different types of blood cells that people need, including red blood cells, white blood cells, and platelets. In a stem cell transplant, the patients own stem cells would be killed by chemotherapy drug and then replaced by stem cells from the donor. Stem cells can be collected from the bone marrow, peripheral blood or umbilical cords. In this study, umbilical cords will be the source of the stem cells.
Currently, large inventories of umbilical cord blood units are available in public banks for transplantation in those lacking bone marrow donors. UCB transplants offer several advantages over adult bone marrow or peripheral blood stem cell transplants, including:
The two main causes of death after umbilical cord blood transplantation for disorders for these kinds of patients, are graft failure and infection.
In this study we are trying to address these two problems by using different drugs to prepare patients for the transplant.
To help improve engraftment (cells begin to grow), we will include the drug Fludarabine to the usually used Busulfan and Cytoxan that the study patients will receive before their transplant.
We will try to decrease the chance of developing graft-versus-host disease (GvHD) by using Cyclosporin A (CSA) and Mycophenolate Mofetil (MMF), instead of Anti-Thymocyte Globulin (ATG) which is normally used.
Patients will be examined to make sure that they meet the requirements of this study. There will be tests of the heart and of the lungs. X-rays will be taken of the lungs and other organs, depending on the disease. An MRI and consultations with different specialists will also be conducted.
Patients also must have a negative pregnancy test before entering this study if they are a woman of childbearing potential. The blood will be tested for viruses and to look at the functioning of the liver and kidneys. The examination also includes HIV testing. If the patient has HIV, they will not be able to be treated on this protocol.
After we have determined that the patient is eligible for treatment on this study and a suitable UCB stem donor has been found, they will have a central line placed.
After placement of the central line, the following chemotherapy will be given to after admission to the hospital:
Stem cell transplant (infusion of the UCB stem cells) - defined as Day 0 of the treatment. All other "numbered" days relate to this infusion date. For example, Day 1 is the first day after the stem cell transplant.
Standard Therapy: Phenytoin will be given according to the standards of the TCH formulary.
Cyclosporin A (CSA) will be given starting 2 days prior to the stem cell infusion. It will be given daily over 2 hours every 12 hours, and then tapered if no GvHD is present.
Administration of Mycophenolate Mofetil (MMF) will start on the day the stem cell infusion is completed, and will continue daily for 45 days unless the patient develops GvHD.
Intravenous Immunoglobulins (IVIG) will be given as per CAGT SOP for infections prophylaxis.
Granulocyte Colony-Stimulating Factor (GCSF) will be given daily starting at Day +7 until ANC is greater than 2,500 for three consecutive days.
Study Evaluation: Patients will have various study evaluations, including blood samples, before and after the transplant.
Follow-Up: After year 1, the patients will be asked to return to the clinic once a year for consultations. These consultations with specialists will be similar to the ones the patients had before their transplant.
Baylor College of Medicine is the lead sponsor of 734 studies on the registry; 110 are open to participants now.
Of its 83 completed or terminated interventional studies of FDA-regulated products, 44 (53%) have results posted.
Counted across the registry records on this site, refreshed daily.
EXCLUSION CRITERIA:
Busulfan, Cytoxan, Fludarabine, Cord Blood Stem Cell Infusion
Drug: Busulfan · Drug: Cytoxan · Drug: Fludarabine · Procedure: Cord Blood Stem Cell Infusion
Day -9, -8, -7 and -6 Patients less than or equal to 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients \>12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses.
Also known as: Busulfex
(50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 2 hours (can be given over 1 to 4 hours as determined by the treating physician). The total dose to be given over 4 days is 200 mg/kg.
Also known as: Cyclophosphamide
40 mg/m2/day IV over 1 hour for patients greater than 10 kg, or 1.3 mg/kg/day for patients less than or equal to 10 kg.
Also known as: Fludera
The cord blood stem cells will be infused on Day 0.
Overall Survival at 100 Days After Umbilical Cord Blood Transplant in Pediatric Patients.
To determine the overall survival rate at 100 days after umbilical cord blood transplant in pediatric patients with myeloid hematological malignancies.
Time frame: 100 days
Overall Survival at 1 Year After Umbilical Cord Blood Transplant in Pediatric Patients.
To determine the overall survival rate at 1 year after umbilical cord blood transplant in pediatric patients with myeloid hematological malignancies.
Time frame: 1 year
Overall Survival at 3 Years After Umbilical Cord Blood Transplant in Pediatric Patients.
To determine the overall survival rate at 3 years after umbilical cord blood transplant in pediatric patients with myeloid hematological malignancies.
Time frame: 3 years
Number of Participants With Platelet Engraftment
Achievement of untransfused platelet count \> 20 x 10\^9/L on three consecutive days
Time frame: Day 42
Incidence of Severe Grade III-IV Acute GvHD at Day 100.
Number of participants with acute GVHD graded by the method of Przepiorka et al, which evaluates skin involvement, lower and upper GI, and liver function (bilirubin), each being graded in stages from 0 to 4, where 0 means no acute GVHD, and 4 is the highest stage of acute GVHD.
Time frame: Day 100
Number of Participants With Chronic GvHD
Number of participants with chronic GVHD graded by the method of Przepiorka et al, which evaluates skin, joints, oral, ocular, hepatic, esophagus, GI, respiratory, platelet, and musculoskeletal involvement, in stages from 0 to 3.
Time frame: 1 year
Number of Participants With Donor Engraftment After Transplant.
To evaluate donor engraftment at 100 days, 6 and 12 months after transplant.
Time frame: 100 days, 6 months and 12 months
Number of Participants With Neutrophil Engraftment
Achievement of absolute neutrophil count \> 0.5 x 10\^9/L on three consecutive days
Time frame: Day 42
| Milestone | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| Started | 40 |
| Completed | 30 |
| Not completed | 10 |
| Withdrew: Death | 6 |
| Withdrew: Lost to follow-up | 3 |
| Withdrew: Possible undiagnosed aml at study entry | 1 |
To determine the overall survival rate at 100 days after umbilical cord blood transplant in pediatric patients with myeloid hematological malignancies.
| probability of overall survival | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| Overall Survival at 100 Days After Umbilical Cord Blood Transplant in Pediatric Patients. | 0.947 (0.806 to 0.987) |
To determine the overall survival rate at 1 year after umbilical cord blood transplant in pediatric patients with myeloid hematological malignancies.
| probability of overall survival | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| Overall Survival at 1 Year After Umbilical Cord Blood Transplant in Pediatric Patients. | 0.868 (0.712 to 0.943) |
To determine the overall survival rate at 3 years after umbilical cord blood transplant in pediatric patients with myeloid hematological malignancies.
| probability of overall survival | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| Overall Survival at 3 Years After Umbilical Cord Blood Transplant in Pediatric Patients. | 0.868 (0.712 to 0.943) |
Achievement of untransfused platelet count \> 20 x 10\^9/L on three consecutive days
| Participants | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| Engrafted | 17 |
| Not engrafted | 20 |
Number of participants with acute GVHD graded by the method of Przepiorka et al, which evaluates skin involvement, lower and upper GI, and liver function (bilirubin), each being graded in stages from 0 to 4, where 0 means no acute GVHD, and 4 is the highest stage of acute GVHD.
| Participants | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| Incidence of Severe Grade III-IV Acute GvHD at Day 100. | 1 |
Number of participants with chronic GVHD graded by the method of Przepiorka et al, which evaluates skin, joints, oral, ocular, hepatic, esophagus, GI, respiratory, platelet, and musculoskeletal involvement, in stages from 0 to 3.
| Participants | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| Number of Participants With Chronic GvHD | 1 |
To evaluate donor engraftment at 100 days, 6 and 12 months after transplant.
| Participants | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| 100 days | 36 |
| 6 months | 33 |
| 12 months | 33 |
Achievement of absolute neutrophil count \> 0.5 x 10\^9/L on three consecutive days
| Participants | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| Engrafted | 37 |
| Not engrafted | 0 |
Collected over We have recorded all grade 3 and 4 toxicities, except hematological toxicities, fever, abnormal glucose, ALT, GGT, and K levels from the day conditioning started until day 30 post-transplant. SAEs were reported up to day 100. Our study primary outcome is Overall Survival (OS) up to 3 years after transplant. The use of AEs up to 100 days is the standard measurement after a stem cell transplant. OS will capture any major toxicity up to 3 years after transplant that will lead to mortality.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Umbilical Cord Blood Transplant Treatment Plan | 6/40 (15%) | 27/40 (67.5%) | 25/40 (62.5%) |
| Event | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| Catheter related infectionMetabolism and nutrition disorders | 8/40 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 4/40 |
| Hepatobiliary disorders - Other, specify: VODRespiratory, thoracic and mediastinal disorders | 3/40 |
| Acute kidney injuryRenal and urinary disorders | 2/40 |
| DyspneaGastrointestinal disorders | 2/40 |
| Multi-organ failureMusculoskeletal and connective tissue disorders | 2/40 |
| Respiratory, thoracic and mediastinal disorders - Other, specify: Respiratory distressRespiratory, thoracic and mediastinal disorders | 2/40 |
| SeizureInfections and infestations | 2/40 |
| Blood and lymphatic system disorders - Other, specify: Thrombotic microangiopathyBlood and lymphatic system disorders | 1/40 |
| Cardiac General - Other: Cardiopulmonary collapse of unknown etiologyCardiac disorders | 1/40 |
| Event | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| HypocalcemiaMetabolism and nutrition disorders | 7/40 |
| Catheter related infectionGastrointestinal disorders | 6/40 |
| Blood bilirubin increasedInfections and infestations | 4/40 |
| HyponatremiaGastrointestinal disorders | 4/40 |
| HypertensionMetabolism and nutrition disorders | 3/40 |
| SeizureVascular disorders | 3/40 |
| Aspartate aminotransferase increasedInvestigations | 2/40 |
| DiarrheaMetabolism and nutrition disorders | 2/40 |
| HypernatremiaMetabolism and nutrition disorders | 2/40 |
| HypertriglyceridemiaMetabolism and nutrition disorders | 2/40 |
The analysis included 38 evaluable participants who completed conditioning and received transplant. Two participants who were enrolled but considered not evaluable for the study were excluded from the analysis. One participant died before receiving transplant. The other was diagnosed with aplastic anemia without signs of malignancy at the time of enrollment, but later showed signs of MDS and progressed to AML, which made the participant not evaluable for this study.
| Age, Continuous(months) | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| Median | 5 (1 to 111) |
| Sex: Female, Male(Participants) | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| Female | 15 |
| Male | 23 |
| Ethnicity (NIH/OMB)(Participants) | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| Hispanic or Latino | 20 |
| Not Hispanic or Latino | 18 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Umbilical Cord Blood Transplant Treatment Plan |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 2 |
| White | 35 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
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