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Double Cord Blood Transplant for Patients With Malignant and Non-malignant Disorders

Primary Purpose

Leukemia, Lymphoma, Neuroblastoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Alemtuzumab
Total Body Irradiation
Melphalan
Busulfan
Phenytoin
Fludarabine
Cyclophosphamide
Horse Antithymocyte Globulin
Rabbit Antithymocyte Globulin
Thiotepa
Sponsored by
Columbia University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring Cord Blood Transplant, Allogeneic Stem Cell Transplant

Eligibility Criteria

undefined - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Columbia Presbyterian Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

A: Full Intensity with TBI

B: Full intensity without TBI

C: Moderate Intensity

D: Reduced Intensity

E: Fanconi's Anemia

F: Regimen for non-malignant diseases

Arm Description

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).

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

Graft Failure Rate
Number of patients to experience graft failure.
Response Rate (Complete and Partial Response)
Response rate to each regimen will be measured.
Overall Survival (OS)
OS will be summarized using the Kaplan and Meier curves.
Disease Free Survival (DFS)
DFS will be summarized using the Kaplan and Meier curves.

Secondary Outcome Measures

Full Information

First Posted
May 5, 2008
Last Updated
March 4, 2019
Sponsor
Columbia University
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1. Study Identification

Unique Protocol Identification Number
NCT00801931
Brief Title
Double Cord Blood Transplant for Patients With Malignant and Non-malignant Disorders
Official Title
Double Umbilical Cord Blood Transplantation for Patients With Malignant and Non-Malignant Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Terminated
Why Stopped
Poor accrual
Study Start Date
September 6, 2007 (Actual)
Primary Completion Date
May 5, 2009 (Actual)
Study Completion Date
May 5, 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Columbia University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma, Neuroblastoma, Immunodeficiencies, Anemia
Keywords
Cord Blood Transplant, Allogeneic Stem Cell Transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A: Full Intensity with TBI
Arm Type
Experimental
Arm Description
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).
Arm Title
B: Full intensity without TBI
Arm Type
Experimental
Arm Description
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.
Arm Title
C: Moderate Intensity
Arm Type
Experimental
Arm Description
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.
Arm Title
D: Reduced Intensity
Arm Type
Experimental
Arm Description
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.
Arm Title
E: Fanconi's Anemia
Arm Type
Experimental
Arm Description
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.
Arm Title
F: Regimen for non-malignant diseases
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Alemtuzumab
Other Intervention Name(s)
Lemtrada, Campath
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Total Body Irradiation
Other Intervention Name(s)
TBI
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
Alkeran
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Busulfex, Myleran
Intervention Description
(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.
Intervention Type
Drug
Intervention Name(s)
Phenytoin
Other Intervention Name(s)
Fosphenytoin, Dilantin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Fludarabine will be given IV in 50-100 ml of D5W or 0.9% sodium chloride, over 30 minutes.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan, Neosar
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Horse Antithymocyte Globulin
Other Intervention Name(s)
Atgam, ATG[horse]
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Rabbit Antithymocyte Globulin
Other Intervention Name(s)
Thymoglobulin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Thiotepa
Other Intervention Name(s)
Tepadina
Intervention Description
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).
Primary Outcome Measure Information:
Title
Graft Failure Rate
Description
Number of patients to experience graft failure.
Time Frame
Up to 2 years
Title
Response Rate (Complete and Partial Response)
Description
Response rate to each regimen will be measured.
Time Frame
Up to 2 years
Title
Overall Survival (OS)
Description
OS will be summarized using the Kaplan and Meier curves.
Time Frame
Up to 2 years
Title
Disease Free Survival (DFS)
Description
DFS will be summarized using the Kaplan and Meier curves.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Prakash Satwani, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia Presbyterian Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States

12. IPD Sharing Statement

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Double Cord Blood Transplant for Patients With Malignant and Non-malignant Disorders

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