Leukemia, Lymphoma, Neuroblastoma, Immunodeficiencies, Anemia
Conditions
Keywords
Cord Blood Transplant, Allogeneic Stem Cell Transplant
Brief summary
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.
Detailed description
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.
Interventions
DRUGAlemtuzumab
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.
RADIATIONTotal Body Irradiation
DRUGMelphalan
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.
DRUGBusulfan
(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.
DRUGPhenytoin
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.
DRUGFludarabine
Fludarabine will be given IV in 50-100 ml of D5W or 0.9% sodium chloride, over 30 minutes.
DRUGCyclophosphamide
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.
DRUGHorse Antithymocyte Globulin
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.
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.
DRUGThiotepa
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).
Sponsors
Columbia University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 30 Years
Healthy volunteers
No
Inclusion criteria
* Patients will be eligible for double cord blood stem cell transplant (TNC ≥ 4x107/kg of two combined units) if available single cord blood has TNC ≤4.0 x 107/kg and they lack a matched (5-6/6) family donor, a 10/10 unrelated adult donor, and/or if their disease status required emergent stem cell transplant and they could not wait 2-3 months for searching for a matched unrelated adult donor. * Adequate renal function defined as:Serum creatinine \<1.5 x normal, or Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>60 ml/min/m2 or \>60 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range. * Adequate liver function defined as:Total bilirubin \<1.5 x normal, or serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase (AST)) or serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase (ALT)) \<3.0 x normal * Adequate cardiac function defined as:Shortening fraction \>27% by echocardiogram, or Ejection fraction \>47% by radionucleotide angiogram or echocardiogram. * Adequate pulmonary function defined as:Uncorrected diffusing capacity of the lungs for carbon monoxide (DLCO) 50% by pulmonary function test.For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \>94% on room air. Eligibility for Moderate Intensity, Reduced Intensity Regimen and Fanconi's Anemia (Regimens C, D and E) * Adequate renal function defined as: Serum creatinine \<2.0 x normal, or Creatinine clearance or radioisotope GFR 40 ml/min/m2 or \>40 ml/min/1.73 m2 or an equivalent GFR as determined by the institutional normal range. * Adequate liver function defined as:Total bilirubin \<2.5 x normal, or SGOT (AST) or SGPT (ALT) \<5.0 x normal * Adequate cardiac function defined as:Shortening fraction of \>25% by echocardiogram, or Ejection fraction \>40% by radionucleotide angiogram or echocardiogram. * Adequate pulmonary function defined as:Uncorrected DLCO \>35% by pulmonary function test. For children who are uncooperative, no evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \>94% on room air.
Exclusion criteria
* Females who are pregnant or breast-feeding * Patients with documented uncontrolled infection at the time of study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Graft Failure Rate | Up to 2 years | Number of patients to experience graft failure. |
| Response Rate (Complete and Partial Response) | Up to 2 years | Response rate to each regimen will be measured. |
| Overall Survival (OS) | Up to 2 years | OS will be summarized using the Kaplan and Meier curves. |
| Disease Free Survival (DFS) | Up to 2 years | DFS will be summarized using the Kaplan and Meier curves. |
Countries
United States
Participant flow
Pre-assignment details
There was only 1 subjected enrolled. The 1 subject was enrolled into Arm - Experimental: C: Moderate Intensity.
Participants by arm
| Arm | Count |
|---|---|
| Experimental: C: Moderate Intensity 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. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Experimental: C: Moderate Intensity |
|---|---|
| Age, Categorical <=18 years | 1 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Disease Free Survival (DFS)
DFS will be summarized using the Kaplan and Meier curves.
Time frame: Up to 2 years
Population: Not enough subjects were enrolled for data analysis.
Primary
Graft Failure Rate
Number of patients to experience graft failure.
Time frame: Up to 2 years
Population: Not enough subjects were enrolled for data analysis.
Primary
Overall Survival (OS)
OS will be summarized using the Kaplan and Meier curves.
Time frame: Up to 2 years
Population: Not enough subjects were enrolled for data analysis.
Primary
Response Rate (Complete and Partial Response)
Response rate to each regimen will be measured.
Time frame: Up to 2 years
Population: Not enough subjects were enrolled for data analysis.