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

Columbia University

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Anemia; Neuroblastoma; Immunodeficiencies; Lymphoma; Leukemia

Treatments: Drug: Busulfan; Drug: Horse Antithymocyte Globulin; Drug: Phenytoin; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rabbit Antithymocyte Globulin; Drug: Melphalan; Drug: Alemtuzumab; Radiation: Total Body Irradiation; Drug: Thiotepa

Study type: Interventional

Funder types: Other

Identifiers

NCT00801931

CHNY-06-533 (Other Identifier)

AAAC3457

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1 patient

Sex: All

Ages: Under 30 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

1 participants in 6 patient groups

A: Full Intensity with TBI

Experimental group

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).

Treatment:

Drug: Thiotepa

Radiation: Total Body Irradiation

Drug: Rabbit Antithymocyte Globulin

Drug: Cyclophosphamide

B: Full intensity without TBI

Experimental group

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.

Treatment:

Drug: Rabbit Antithymocyte Globulin

Drug: Busulfan

Drug: Melphalan

C: Moderate Intensity

Experimental group

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.

Treatment:

Drug: Alemtuzumab

Drug: Fludarabine

Drug: Busulfan

D: Reduced Intensity

Experimental group

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.

Treatment:

Drug: Rabbit Antithymocyte Globulin

Drug: Fludarabine

Drug: Busulfan

E: Fanconi's Anemia

Experimental group

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.

Treatment:

Radiation: Total Body Irradiation

Drug: Fludarabine

Drug: Cyclophosphamide

Drug: Horse Antithymocyte Globulin

F: Regimen for non-malignant diseases

Experimental group

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.

Treatment:

Drug: Rabbit Antithymocyte Globulin

Drug: Cyclophosphamide

Drug: Busulfan

Drug: Phenytoin