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

NCT00801931 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: AAAC3457CHNY-06-533
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia; Lymphoma; Neuroblastoma; Immunodeficiencies; Anemia

Keywords

Cord Blood Transplant; Allogeneic Stem Cell Transplant

Outcome Measures

Primary Outcomes (4)

• Graft Failure Rate

  Number of patients to experience graft failure.

  Up to 2 years

• Response Rate (Complete and Partial Response)

  Response rate to each regimen will be measured.

  Up to 2 years

• Overall Survival (OS)

  OS will be summarized using the Kaplan and Meier curves.

  Up to 2 years

• Disease Free Survival (DFS)

  DFS will be summarized using the Kaplan and Meier curves.

  Up to 2 years

Study Arms (6)

A: Full Intensity with TBI

EXPERIMENTAL

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

B: Full intensity without TBI

EXPERIMENTAL

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

C: Moderate Intensity

EXPERIMENTAL

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

D: Reduced Intensity

EXPERIMENTAL

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

E: Fanconi's Anemia

EXPERIMENTAL

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

F: Regimen for non-malignant diseases

EXPERIMENTAL

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

Interventions

Alemtuzumab DRUG

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

C: Moderate Intensity

Total Body Irradiation RADIATION

Also known as: TBI

A: Full Intensity with TBI; E: Fanconi's Anemia

Melphalan DRUG

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

B: Full intensity without TBI

Busulfan DRUG

(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

B: Full intensity without TBI; C: Moderate Intensity; D: Reduced Intensity; F: Regimen for non-malignant diseases

Phenytoin DRUG

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

F: Regimen for non-malignant diseases

Fludarabine DRUG

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

Also known as: Fludara

C: Moderate Intensity; D: Reduced Intensity; E: Fanconi's Anemia

Cyclophosphamide DRUG

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

A: Full Intensity with TBI; E: Fanconi's Anemia; F: Regimen for non-malignant diseases

Horse Antithymocyte Globulin DRUG

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]

E: Fanconi's Anemia

Rabbit Antithymocyte Globulin DRUG

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

A: Full Intensity with TBI; B: Full intensity without TBI; D: Reduced Intensity; F: Regimen for non-malignant diseases

Thiotepa DRUG

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

A: Full Intensity with TBI

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• Females who are pregnant or breast-feeding
• Patients with documented uncontrolled infection at the time of study entry

Sponsors & Collaborators

• Columbia University: lead

Study Sites (1)

Columbia Presbyterian Medical Center

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Leukemia; Lymphoma; Neuroblastoma; Immunologic Deficiency Syndromes; Anemia

Interventions

Alemtuzumab; Whole-Body Irradiation; Melphalan; Busulfan; Phenytoin; fosphenytoin; fludarabine; fludarabine phosphate; Cyclophosphamide; Antilymphocyte Serum; thymoglobulin; Thiotepa

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Investigative Techniques; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Butylene Glycols; Glycols; Alcohols; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Hydantoins; Imidazolidines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Immune Sera; Biological Products; Complex Mixtures; Triethylenephosphoramide; Aziridines; Azirines

Limitations and Caveats

There was only 1 subjected enrolled. The 1 subject was enrolled into Arm - Experimental: C: Moderate Intensity.

Results Point of Contact

• Title: Prakash Satwani, MD
• Organization: Columbia University

ps2087@cumc.columbia.edu

212-305-0223

Study Officials

• Prakash Satwani, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics at the Columbia University Med, Department of Pediatrics BMT

Study Record Dates

• First Submitted: May 5, 2008
• First Posted: December 4, 2008
• Study Start: September 6, 2007
• Primary Completion: May 5, 2009
• Study Completion: May 5, 2009
• Last Updated: March 27, 2019
• Results First Posted: March 27, 2019

Record last verified: 2019-03

Locations

US (1)