A Phase 1/2 interventional study of Alemtuzumab and Total Body Irradiation in Leukemia, Lymphoma and Neuroblastoma, sponsored by Columbia University. Terminated at 1 site in United States. Open to participants aged Up to 30 Years. Per ClinicalTrials.gov, last updated 2019-03-27.
Sponsored by Columbia University · Phase 1/2, Interventional, and Treatment
The purpose of this study is to determine the safety and toxicity and feasibility of double umbilical cord blood transplantation (DUCBT) in patients with selected malignant and non-malignant, and to quantify the percentage and donor sources of mixed donor chimerism following DUCBT in patients with selected malignant and non-malignant disorders.
Allogeneic stem cell transplantation from an human leukocyte antigen (HLA) matched related family donor is the treatment of choice for a wide variety of malignant and non-malignant disorders. Unfortunately, only 25% of potential recipients have an HLA matched related family donor, leaving approximately 75% of potential recipients requiring alternative sources of HLA matched allogeneic stem cells. One potential source of HLA matched allogeneic stem cells is from unrelated adult donors that have been identified in the national and international donor registries. However, several limitations restrict the uniform utilization of unrelated allogeneic adult donors including ethnic background of the recipient, acuity and timing of planned allogeneic transplant, availability of donor, and high risk of severe acute graft-versus-host disease (GVHD) (III/IV), among others. The investigators have recently identified a new alternative source of allogeneic stem cells, unrelated cryopreserved placental/cord blood stem cells.
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This study's enrollment of 1 is below the median of 32 across 475 interventional studies indexed under Neuroblastoma.
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Eligibility for Moderate Intensity, Reduced Intensity Regimen and Fanconi's Anemia (Regimens C, D and E)
Exclusion Criteria:
Patients will start their pre-conditioning regimen on Day -8. Fractionated total body irradiation (TBI) will be administered twice daily for 3 days on Days -8, -7, and -6. Patients will receive Thiotepa on Days -5 and-4, Cyclophosphamide on Days -3 and -2 and- rabbit antithymocyte globulin on Days -4, -3, -2 and -1.The double cord blood infusion will be performed on Day 0. GM-CSF hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus/mycophenolate mofetil (MMF).
Radiation: Total Body Irradiation · Drug: Cyclophosphamide · Drug: Rabbit Antithymocyte Globulin · Drug: Thiotepa
Patients will start their pre-conditioning regimen on Day -9. Patients will receive busulfan twice daily on Days - 8, -7, -6, and -5 and Melphalan on Days -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2 and -1 with double cord blood infusion on Day 0. Granulocyte-macrophage colony-stimulating factor (GM-CSF) hematopoietic growth factor will start on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
Drug: Melphalan · Drug: Busulfan · Drug: Rabbit Antithymocyte Globulin
Patients will start their GVHD prophylaxis with Tacrolimus on Day -8. Patients will receive busulfan twice daily on Days -8, -7, -6, and -5; fludarabine on Days -7, -6, -5, -4, -3 and -2 and alemtuzumab on Days -5, -4, -3, -2, and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
Drug: Alemtuzumab · Drug: Busulfan · Drug: Fludarabine
Patients will start their GVHD prophylaxis with Tacrolimus on Day -6. Patients will receive busulfan twice daily on Days -6, and-5; fludarabine on Days -6, -5, -4, -3 and -2 and rabbit antithymocyte globulin on Days -4, -3, -2, and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
Drug: Busulfan · Drug: Fludarabine · Drug: Rabbit Antithymocyte Globulin
Patients will start their pre-conditioning regimen on Day -6. Patients will receive TBI as a single fraction on Day -6. Patients will receive fludarabine and cyclophosphamide on Days - 5, -4, -3, and -2 and horse antithymocyte globulin on Days -5, -4, -3, -2 and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
Radiation: Total Body Irradiation · Drug: Fludarabine · Drug: Cyclophosphamide · Drug: Horse Antithymocyte Globulin
Patients will begin fosphenytoin or phenytoin prophylaxis on Day -10. Patients will receive busulfan on days -9, -8, -7 and -6, cyclophosphamide on days -5, -4, -3, and -2 and rabbit antithymocyte globulin on days -4, -3, -2 and -1. The double cord blood infusion will be performed on Day 0. GVHD prophylaxis will consist of tacrolimus/MMF.
Drug: Busulfan · Drug: Phenytoin · Drug: Cyclophosphamide · Drug: Rabbit Antithymocyte Globulin
Each dose of alemtuzumab is to be diluted in 5% dextrose in water (D5W) or normal saling (NS) (maximum concentration: 0.3 mg/mL) for intravenous (IV) infusion over two hours.
Also known as: Lemtrada, Campath
Also known as: TBI
Melphalan 45mg/m2 (1.5 mg/kg IV for children \<1 year of age or \<10 kg) diluted in 0.9% NS to a concentration of 0.1- 0.45mg/ml, given IV over 30 minutes.
Also known as: Alkeran
(Busulfex) will be given IV in 0.9% sodium chloride or D5W to a final solution for infusion equal to 10 times the volume of diluent to Busulfex (to a concentration \>0.5 mg/mL), through a central venous access device over 2 hours.
Also known as: Busulfex, Myleran
Fosphenytoin can be administered in D5W or 0.9% sodium chloride to a final concentration ranging from 1.5 to 25 mg PE/ml at a rate of 1-3 mg phenytoin sodium equivalents (PE)/kg/min up to 50-150 mg PE/minute.
Also known as: Fosphenytoin, Dilantin
Fludarabine will be given IV in 50-100 ml of D5W or 0.9% sodium chloride, over 30 minutes.
Also known as: Fludara
Cyclophosphamide should be infused over one hour. The drug can be diluted in D5W, NS, or other solutions (100-250 mL) to a maximum concentration of 20 mg/mL.
Also known as: Cytoxan, Neosar
Horse Antithymocyte Globulin (ATG \[horse\]) will be diluted in 0.9% sodium chloride or 0.45% sodium chloride for IV infusion (through an inline filter with pore size of 0.2 micrometer) to a concentration of 1-4 mg/ml and infused through a central venous catheter over 8 hours in Regimen E.
Also known as: Atgam, ATG[horse]
Rabbit Anti-Thymocyte Globulin (rabbit ATG) will be diluted in 0.9% sodium chloride or D5W for IV infusion (through an in-line filter with pore size of 0.22 micrometer) to a concentration of 0.5 mg/ml and infused through a central venous catheter over 8 hours for all doses on Days -4, -3, -2, and -1 in Regimens A, B, D and F.
Also known as: Thymoglobulin
Thiotepa should be diluted in NS (1-5 mg/ml) and infused over 2 hrs on Days -8, -4. IV fluids should be at maintenance rate (1500 ml/m2).
Also known as: Tepadina
Graft Failure Rate
Number of patients to experience graft failure.
Time frame: Up to 2 years
Response Rate (Complete and Partial Response)
Response rate to each regimen will be measured.
Time frame: Up to 2 years
Overall Survival (OS)
OS will be summarized using the Kaplan and Meier curves.
Time frame: Up to 2 years
Disease Free Survival (DFS)
DFS will be summarized using the Kaplan and Meier curves.
Time frame: Up to 2 years
| Milestone | Experimental: C: Moderate Intensity |
|---|---|
| Started | 1 |
| Completed | 1 |
| Not completed | 0 |
Number of patients to experience graft failure.
No measurements were reported for this outcome.
Response rate to each regimen will be measured.
No measurements were reported for this outcome.
OS will be summarized using the Kaplan and Meier curves.
No measurements were reported for this outcome.
DFS will be summarized using the Kaplan and Meier curves.
No measurements were reported for this outcome.
Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Experimental: C: Moderate Intensity | 1/1 (100%) | 1/1 (100%) | 0/1 (0%) |
| Event | Experimental: C: Moderate Intensity |
|---|---|
| Respiratory Failure with Cardiac TamponadeRespiratory, thoracic and mediastinal disorders | 1/1 |
There was only 1 subjected enrolled. The 1 subject was enrolled into Arm - Experimental: C: Moderate Intensity.
| Age, Categorical(Participants) | Experimental: C: Moderate Intensity |
|---|---|
| <=18 years | 1 |
| Between 18 and 65 years | 0 |
| >=65 years | 0 |
| Sex: Female, Male(Participants) | Experimental: C: Moderate Intensity |
|---|---|
| Female | 1 |
| Male | 0 |
| Ethnicity (NIH/OMB)(Participants) | Experimental: C: Moderate Intensity |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 1 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Experimental: C: Moderate Intensity |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 0 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
This study is terminated, as verified in Mar 2019. You cannot join it, but the record below documents what was studied.
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Columbia University