Unrelated Umbilical Cord Blood Transplantation Augmented With ALDHbr Umbilical Cord Blood Cells

NCT00692926 | Completed Phase 1 DMC

• 2 other identifiers: Pro000089707177
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this investigational (not approved by the FDA) Phase I research is to test whether transplantation of umbilical cord blood cells can be safely supplemented with a transfusion of a portion of these cells that have been sorted (collected from a special machine called a cell sorter) and then either infused a few hours after the standard transplant or for some patients grown in a special system in the laboratory prior to the transplant, designed to increase the number of stem cells transplanted. This system is currently in the early phases of testing.

Conditions

MDS; Anemia, Aplastic; Inborn Errors of Metabolism; Congenital Marrow Failure; Congenital Immunodeficiency Syndrome

Keywords

ALDHbr; Umbilical Cord Blood; Transplantation; Hematological malignancy; MDS; severe aplastic anemia; inborn error of metabolism; congenital marrow failure or congenital immunodeficiency syndrome; Hurler's Disease; Tay Sach's; PMD; Hunter's Syndrome; Krabbe; MLD; ALD; ALL; AML

Outcome Measures

Primary Outcomes (1)

• To assess the safety of infusing ex vivo cytokine-primed ALDHbr cells isolated from banked unrelated umbilical cord blood (CB) into patients also receiving a standard unmanipulated unrelated CB transplant delivering >2.5x10e7 nucleated cells per kg.

  Prospective

Secondary Outcomes (2)

• To describe the biological effect of ex vivo cytokine-primed ALDHbr cells in these patients on neutrophil and platelet engraftment and immune reconstitution.

  prospective

• To describe the clinical outcomes in these patients: - incidence of infections -Non relapse mortality -incidence of acute and chronic graft-vs-host disease -overall survival at 180 days

  prospective

Study Arms (4)

20% primed UCB

OTHER

20% of UCB is ALDHbr sorted and primed and give on transplant day after conventional graft

Biological: ALDHbr Umbilical Cord Blood Cells

20% un-primed

OTHER

20% of UCB is ALDHbr freshly sorted and give on transplant day 4-8 hrs after conventional graft

Biological: ALDHbr Umbilical Cord Blood Cells

Double- 1 unit primed

OTHER

patient receives 1 conventional UCB unit and 1 unit that has been ALDHbr sorted and primed

Biological: ALDHbr Umbilical Cord Blood Cells

Double- 1 unit unprimed

OTHER

Patient receives 1 UCB unit and a second UCB unit that has been freshly ALDHbr sorted

Biological: ALDHbr Umbilical Cord Blood Cells

Interventions

ALDHbr Umbilical Cord Blood Cells BIOLOGICAL

ALDHbr sorted Umbilical Cord Blood Cells

20% primed UCB; 20% un-primed; Double- 1 unit primed; Double- 1 unit unprimed

Eligibility Criteria

• Age: Up to 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Hematologic Malignancy: High risk ALL in first complete remission ALL or ANLL in second or subsequent remission ANLL in relapse MDS CML in any chronic phase or accelerated phase Severe aplastic anemia refractory to medical therapy The subject is negative for CNS disease at time of enrollment.
• Inborn errors of metabolism Hurler Syndrome (MPS I) Hurler-Scheie Syndrome Hunter Syndrome (MPS II) Sanfilippo Syndrome (MPS III) Morquio Syndrome (MPS IV) Maroteaux-Lamy Syndrome (MPS VI) Krabbe Disease (Globoid Leukodystrophy) Metachromatic Leukodystrophy (MLD) Adrenoleukodystrophy(ALD and AMN) Sandhoff Disease Tay Sachs Disease The subject does NOT have uncontrolled seizures, apnea, evidence of aspiration pneumonia or evidence of brain stem involvement on MRI scans
• Congenital marrow failure Amegakaryocytic thrombocytopenia TAR Kostmann's Syndrome Schwachman-Diamond Syndrome Blackfan-Diamond Anemia
• Congenital immunodeficiency syndromes requiring myeloablative therapy Wiscott Aldrich Syndrome LAD CGD FEL/HLH CVID/CID
• SUBJECT'S DONOR Subject does NOT have a 6/6 or 5/6 antigen matched related bone marrow donor. Suitably matched cord blood unit with adequate cell dose is available. Unit must be in a dual compartment bag.
• PERFORMANCE STATUS and ORGAN FUNCTION
• \<55 years of age at time of enrollment.
• Lansky score between 60% and 100%, or a Karnofsky score between 50% and 100%
• Adequate function of other organ systems
• Creatinine \< 2.0 mg/dl and creatinine clearance \> 50 cc/min/m2
• Hepatic transaminases (ALT/AST) \< 4 x normal, bilirubin \< 2.0 mg/dl
• Normal cardiac function by echocardiogram or radionuclide scan
• Pulmonary function tests demonstrating FVC, CVC, and FEV1 of \>60% of predicted for age. For adult patients DLCO \> 60% of predicted. If patient cannot perform PFTs, clearance by the pediatric or adult pulmonologist will be required
• No uncontrolled infections at the time of cytoreduction
• NOT pregnant or lactating (must have a current negative pregnancy test)

Sponsors & Collaborators

• Joanne Kurtzberg, MD: lead
• Aldagen: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Anemia, Aplastic; Metabolism, Inborn Errors; Primary Immunodeficiency Diseases; Hematologic Neoplasms; Mucopolysaccharidosis I; Mucopolysaccharidosis II

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neoplasms by Site; Neoplasms; Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Heredodegenerative Disorders, Nervous System

Study Officials

• Joanne Kurtzberg, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Pediatrics

Study Record Dates

• First Submitted: June 3, 2008
• First Posted: June 6, 2008
• Study Start: October 1, 2005
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: June 29, 2017

Record last verified: 2017-06

Locations

US (1)