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Umbilical Cord Blood Transplant for Congenital Pediatric Disorders (UCB)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Baylor College of Medicine
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
Information provided by (Responsible Party):
Caridad Martinez, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00950846
First received: July 30, 2009
Last updated: September 17, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to determine the safety and effectiveness of Umbilical Cord Blood Transplant (UCBT) to treat the patient's disease, and to see if this treatment can decrease the incidence of GVHD.

This study is for patients that were born with a disease that affects their body's metabolism or immune system. The doctor plans to treat the patient for this illness with a stem cell transplant.

While improved medical care has allowed many people with these diseases to live longer, the only way to truly cure the diseases is by means of a stem cell transplant from a donor who does not have the disease. A stem cell transplant will replace sick cells with new healthy donor cells. Stem cells grow into different types of blood cells that people need, including red blood cells, white blood cells, and platelets. In a stem cell transplant, the patients own stem cells would be killed by chemotherapy drug and then replaced by stem cells from the donor. Stem cells can be collected from the bone marrow, peripheral blood or umbilical cords. In this study, umbilical cords will be the source of the stem cells.

Currently, large inventories of umbilical cord blood units are available in public banks for transplantation in those lacking bone marrow donors. UCB transplants offer several advantages over adult bone marrow or peripheral blood stem cell transplants, including:

  1. Rapid availability,
  2. Absence of donor risk,
  3. Low risk of transmissible infectious diseases,
  4. Low risk of acute GvHD (as compared to recipients of unrelated donor marrow and peripheral blood cells).

The two main causes of death after umbilical cord blood transplantation for disorders for these kinds of patients, are graft failure and infection.

In this study we are trying to address these two problems by using different drugs to prepare patients for the transplant.

To help improve engraftment (cells begin to grow), we will include the drug fludarabine to the usually used busulfan and cytoxan that the study patients will receive before their transplant.

We will try to decrease the chance for infections by using Mycophenolate Mofetil (MMF) instead of Anti-Thymocyte Globulin (ATG) which is normally used.


Condition Intervention
Congenital Pediatric Disorders
Drug: Busulfan
Drug: Cytoxan
Drug: Fludarabine
Procedure: Cord Blood Stem Cell Infusion

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Umbilical Cord Blood Transplant for Congenital Pediatric Disorders

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Overall survival at 1 year after umbilical cord blood transplant in pediatric patients with congenital diseases. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Neutrophil and platelet count recovery at Day 42. [ Time Frame: Day 42 ] [ Designated as safety issue: Yes ]
  • Incidence of severe Grade III-IV acute GvHD at Day 100. [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
  • Incidence of chronic GvHD at 1 year. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
  • Engraftment of donor cells at 100 days, 6 months, and 12 months after transplant. [ Time Frame: 100 days, 6 months and 12 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 22
Study Start Date: July 2009
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Umbilical Cord Blood Transplant Treatment Plan
Busulfan, Cytoxan, Fludarabine, Cord Blood Stem Cell Infusion
Drug: Busulfan

Day -9, -8, -7 and -6

Patients less than or equal to 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses.

Other Name: Busulfex
Drug: Cytoxan
(50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 2 hours (can be given over 1 to 4 hours as determined by the treating physician). The total dose to be given over 4 days is 200 mg/kg.
Other Name: Cyclophosphamide
Drug: Fludarabine
40 mg/m2/day IV over 1 hour for patients greater than 10 kg, or 1.3 mg/kg/day for patients less than or equal to 10 kg.
Other Name: Fludera
Procedure: Cord Blood Stem Cell Infusion
The cord blood stem cells will be infused on Day 0.

Detailed Description:

Patients will be examined to make sure that they meet the requirements of this study. There will be tests of the heart and of the lungs. X-rays will be taken of the lungs and other organs, depending on the disease. An MRI and consultations with different specialists will also be conducted.

Patients also must have a negative pregnancy test before entering this study if they are a woman of childbearing potential. The blood will be tested for viruses and to look at the functioning of the liver and kidneys. The examination also includes HIV testing. If the patient has HIV, they will not be able to be treated on this protocol.

After we have determined that the patient is eligible for treatment on this study and a suitable UCB stem donor has been found, they will have a central line placed.

After placement of the central line, the following chemotherapy will be given to after admission to the hospital:

  • 9 days before the infusion through 6 days before the infusion: Busulfan every 6 hours for 16 total doses.
  • 5 days before the infusion through 2 days before the infusion: Cytoxan given daily for 4 days over 2 hours. (It can be given over 1 to 4 hours if needed as decided by the physician). Mesna will be given per standards.
  • 4 days before the infusion through 1 day before the infusion: Fludarabine given daily for 4 days over 1 hour.

Stem cell transplant (infusion of the UCB stem cells) - defined as Day 0 of the treatment. All other "numbered" days relate to this infusion date. For example, Day 1 is the first day after the stem cell transplant.

Standard Therapy: Phenytoin will be given according to the standards of the TCH formulary.

Cyclosporin A (CSA) will be given starting 2 days prior to the stem cell infusion. It will be given daily over 2 hours every 12 hours, and then tapered if no GVHD is present.

Administration of Mycophenolate Mofetil (MMF) will start on the day the stem cell infusion is completed, and will continue daily for 45 days unless the patient develops GvHD.

Intravenous Immunoglobulins (IVIG) will be given as per CAGT SOP for infections prophylaxis.

Study Evaluation: Patients will have various study evaluations, including blood samples, before and after the transplant.

Follow-Up: After year 1, the patients will be asked to return to the clinic once a year for consultations. These consultations with specialists will be similar to the ones the patients had before their transplant.

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Patients less than 18 years of age.
  • Recipients of umbilical cord blood transplantation (i.e. HLA matched or mismatched / related or unrelated) with a congenital immunologic or metabolic pediatric disease for which Stem cell transplantation has been beneficial.
  • Related or Unrelated Umbilical Cord Blood Unit with 0-1 antigen mismatch, 5-6 HLA- A and B (at low to intermediate resolution) and DRB1 (at high resolution).
  • Total cryopreserved HSC graft cell dose must be 5 x 10^7 or greater nucleated cells per kilogram recipient body weight.
  • Lansky/Karnofsky scores 60 or greater.
  • Patient has DLCO > 50% predicted or FEV1 > 50%, if applicable.
  • Written informed consent and/or signed assent line from patient, parent or guardian.

EXCLUSION CRITERIA:

  • Patients with uncontrolled infections as assessed by the principal investigator only. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to starting conditioning. For fungal infections patients must be receiving definitive systemic antifungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.
  • Severe renal disease (creatinine > 3X normal for age).
  • Severe hepatic disease (direct bilirubin > 3 mg/dL or SGOT > 500).
  • Patients with symptomatic cardiac failure unrelieved by medical therapy or evidence of significant cardiac dysfunction by echocardiogram (shortening fraction < 20%).
  • HIV positive.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00950846

Contacts
Contact: Caridad Martinez, MD 832-824-4692 camartin@txch.org

Locations
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Caridad A Martinez, MD    832-824-4692    camartin@txch.org   
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
Texas Children's Hospital
Investigators
Principal Investigator: Caridad Martinez, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Caridad Martinez, Assistant Professor, Pediatric Hematology/Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00950846     History of Changes
Other Study ID Numbers: 25064-UCB
Study First Received: July 30, 2009
Last Updated: September 17, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
Congenital Pediatric Disorders
Umbilical Cord Blood Transplant
Congenital Abnormalities
Cord Blood Stem Cell Transplantation
Busulfan
Cytoxan
Cyclophosphamide
Fludarabine

Additional relevant MeSH terms:
Disease
Pathologic Processes
Busulfan
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014