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Trial record 69 of 107 for:    PHENYTOIN

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00801931
Recruitment Status : Terminated (Poor accrual)
First Posted : December 4, 2008
Results First Posted : March 27, 2019
Last Update Posted : March 27, 2019
Sponsor:
Information provided by (Responsible Party):
Prakash Satwani, Columbia University

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.

Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Neuroblastoma Immunodeficiencies Anemia Drug: Alemtuzumab Radiation: Total Body Irradiation Drug: Melphalan Drug: Busulfan Drug: Phenytoin Drug: Fludarabine Drug: Cyclophosphamide Drug: Horse Antithymocyte Globulin Drug: Rabbit Antithymocyte Globulin Drug: Thiotepa Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Double Umbilical Cord Blood Transplantation for Patients With Malignant and Non-Malignant Disorders
Actual Study Start Date : September 6, 2007
Actual Primary Completion Date : May 5, 2009
Actual Study Completion Date : May 5, 2009

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: A: Full Intensity with TBI
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
Other Name: TBI

Drug: Cyclophosphamide
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.
Other Names:
  • Cytoxan
  • Neosar

Drug: Rabbit Antithymocyte Globulin
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.
Other Name: Thymoglobulin

Drug: Thiotepa
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).
Other Name: Tepadina

Experimental: B: Full intensity without TBI
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
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.
Other Name: Alkeran

Drug: Busulfan
(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.
Other Names:
  • Busulfex
  • Myleran

Drug: Rabbit Antithymocyte Globulin
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.
Other Name: Thymoglobulin

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.
Drug: Alemtuzumab
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.
Other Names:
  • Lemtrada
  • Campath

Drug: Busulfan
(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.
Other Names:
  • Busulfex
  • Myleran

Drug: Fludarabine
Fludarabine will be given IV in 50-100 ml of D5W or 0.9% sodium chloride, over 30 minutes.
Other Name: Fludara

Experimental: D: Reduced Intensity
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
(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.
Other Names:
  • Busulfex
  • Myleran

Drug: Fludarabine
Fludarabine will be given IV in 50-100 ml of D5W or 0.9% sodium chloride, over 30 minutes.
Other Name: Fludara

Drug: Rabbit Antithymocyte Globulin
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.
Other Name: Thymoglobulin

Experimental: E: Fanconi's Anemia
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
Other Name: TBI

Drug: Fludarabine
Fludarabine will be given IV in 50-100 ml of D5W or 0.9% sodium chloride, over 30 minutes.
Other Name: Fludara

Drug: Cyclophosphamide
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.
Other Names:
  • Cytoxan
  • Neosar

Drug: Horse 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.
Other Names:
  • Atgam
  • ATG[horse]

Experimental: F: Regimen for non-malignant diseases
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
(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.
Other Names:
  • Busulfex
  • Myleran

Drug: Phenytoin
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.
Other Names:
  • Fosphenytoin
  • Dilantin

Drug: Cyclophosphamide
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.
Other Names:
  • Cytoxan
  • Neosar

Drug: Rabbit Antithymocyte Globulin
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.
Other Name: Thymoglobulin




Primary Outcome Measures :
  1. Graft Failure Rate [ Time Frame: Up to 2 years ]
    Number of patients to experience graft failure.

  2. Response Rate (Complete and Partial Response) [ Time Frame: Up to 2 years ]
    Response rate to each regimen will be measured.

  3. Overall Survival (OS) [ Time Frame: Up to 2 years ]
    OS will be summarized using the Kaplan and Meier curves.

  4. Disease Free Survival (DFS) [ Time Frame: Up to 2 years ]
    DFS will be summarized using the Kaplan and Meier curves.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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): NCT00801931


Locations
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United States, New York
Columbia Presbyterian Medical Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Investigators
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Principal Investigator: Prakash Satwani, MD Columbia University

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Responsible Party: Prakash Satwani, Associate Professor of Pediatrics at the Columbia University Med, Department of Pediatrics BMT, Columbia University
ClinicalTrials.gov Identifier: NCT00801931     History of Changes
Other Study ID Numbers: AAAC3457
CHNY-06-533 ( Other Identifier: CU )
First Posted: December 4, 2008    Key Record Dates
Results First Posted: March 27, 2019
Last Update Posted: March 27, 2019
Last Verified: March 2019

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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

Keywords provided by Prakash Satwani, Columbia University:
Cord Blood Transplant
Allogeneic Stem Cell Transplant

Additional relevant MeSH terms:
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Phenytoin
Immunologic Deficiency Syndromes
Neuroblastoma
Immune System Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Cyclophosphamide
Fludarabine phosphate
Melphalan
Busulfan
Thymoglobulin
Thiotepa
Antilymphocyte Serum
Fludarabine
Alemtuzumab
Vidarabine
Fosphenytoin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents