Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies (UCAML)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Baylor College of Medicine
Sponsor:
Collaborators:
Texas Children's Hospital
Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by (Responsible Party):
Caridad Martinez, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT01247701
First received: November 22, 2010
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

In the study the investigators will use busulfan and cyclophosphamide (BuCy) backbone with the addition of fludarabine as the preparative Stem Cell Transplant (SCT) regimen. As an attempt to improve engraftment rate and reduce infections the investigators are going to incorporate fludarabine in the conditioning regimen. The use of a BuCy backbone has been widely used and comparable to total body irradiation and cyclophosphamide (Cy/TBI) regimen.

Encouraging data on adding fludarabine to the SCT regimen have been reported. A fludarabine-based, conditioning regimen, with adequate immunosuppressive activity could conceivably allow engraftment of stem cells from alternative donors in hematologic malignancies patients with acceptable engraftment rates and low transplant-related mortality. Regimen-related toxicity is believed to be a major contributing factor to GVHD. Therefore this approach may also lead to reduced GVHD, as some investigators have suggested.

In our study as an attempt to decrease the rate of viral infection and reactivation, the investigators will avoid ATG (Thymoglobulin) / Campath (anti-CD52) and instead administer Mycophenolate Mofetil (MMF). The addition of fludarabine should compensate any increase risk of graft failure with the removal of the ATG/Campath. The investigators anticipate that the removal of ATG/Campath will facilitate immune reconstitution more efficiently after receiving a UCBT.


Condition Intervention
Myeloid Hematological Malignancies
Drug: Busulfan
Drug: Cyclophosphamide
Drug: Fludarabine
Procedure: Cord Blood Stem Cell Infusion

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies (UCAML)

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Overall survival at 1 year after UCB transplant in pediatric patients [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To determine the overall survival rate at 1 year after umbilical cord blood transplant in pediatric patients with myeloid hematological malignancies.


Secondary Outcome Measures:
  • Number of participants with severe acute GVHD grade III-IV as an assessment of safety [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    To estimate the risk of severe grade III-IV acute GvHD at day 100.

  • Number of participants with chronic GvHD as an assessment of safety [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    To estimate the risk of chronic GvHD at 1 year.

  • Assess relapse rate after transplant [ Time Frame: 1 and 3 years ] [ Designated as safety issue: Yes ]
    To assess relapse rate at 1 and 3 years after transplant.

  • To evaluate donor engraftment after transplant [ Time Frame: 100 days, 6, 9, 12, 24 and 36 months ] [ Designated as safety issue: No ]
    To evaluate donor engraftment at 100 days, 6, 9, 12, 24, and 36 months after transplant.

  • Assessment of platelet count recovery [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    To determine platelet count recovery at day 42 post transplant

  • Assessment of neutrophil count recovery [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    To determine neutrophil count recovery at day 42 post transplant


Estimated Enrollment: 20
Study Start Date: November 2010
Estimated Study Completion Date: November 2020
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Umbilical Cord Blood Transplant Treatment Plan
Busulfan, Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion
Drug: Busulfan
Busulfan dosing will be as follows: patients <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. It will be given on days -9, -8, -7 and -6.
Other Name: Busulfex
Drug: Cyclophosphamide
Cyclophosphamide (50 mg/kg/dose) will be given IV on day -5, - 4, -3, and -2 over 2 hours. The total dose to be given over 4 days is 200 mg/kg.
Other Name: CTX, Cytoxan
Drug: Fludarabine
Fludarabine 40 mg/m^2 will be given I.V. daily over 1 hour on day -3, -2 and -1.
Other Name: Fludera
Procedure: Cord Blood Stem Cell Infusion
The cord blood stem cells will be infused on day 0.

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a myeloid hematologic malignancy (acute myelogenous leukemia, secondary myelogenous leukemia or myelodysplastic syndrome) unlikely to be cure by standard chemotherapy. This includes patients who have relapsed after standard chemotherapy treatments and patients in first remission with unfavorable prognostics features.
  • Related or Unrelated Umbilical Cord Blood Unit with 0-1 antigen mismatch at HLA-A and B (at low resolution) and DRB1 (at high resolution) with a total nucleated cell dose of ≥ 4x10^7/kg
  • Lansky/Karnofsky scores at least 60
  • Written informed consent and/or signed assent line from patient, parent or guardian.
  • Negative Pregnancy Test, if applicable

Exclusion Criteria:

  • Patients with uncontrolled infections. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. 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 > x 3 normal for age)
  • Severe hepatic disease (direct bilirubin > 3 mg/dl or SGOT > 500)
  • Patient has DLCO < 50% predicted or FEV1 < 50% of predicted, if applicable
  • 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: NCT01247701

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
Texas Children's Hospital
Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators
Principal Investigator: Caridad A Martinez, MD Baylor College of Medicine
Principal Investigator: Robert A Krance, 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: NCT01247701     History of Changes
Other Study ID Numbers: 26558-UCAML
Study First Received: November 22, 2010
Last Updated: March 24, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Baylor College of Medicine:
UCB
Umbilical Cord Blood
Transplant
Umbilical Cord Blood Transplant
Cord Blood Stem Cell Transplantation
Pediatric
Myeloid Hematological Malignancies
Busulfan
Cytoxan
Cyclophosphamide
Fludarabine

Additional relevant MeSH terms:
Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Hematologic Diseases
Busulfan
Cyclophosphamide
Fludarabine monophosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 22, 2014