Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies

NCT01247701 | Completed Results DMC

• 1 other identifier: 26558-UCAML
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

In this 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 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.

Conditions

Myeloid Hematological Malignancies

Keywords

UCB; Umbilical Cord Blood; Transplant; Umbilical Cord Blood Transplant; Cord Blood Stem Cell Transplantation; Pediatric; Myeloid Hematological Malignancies; Busulfan; Cytoxan; Cyclophosphamide; Fludarabine

Outcome Measures

Primary Outcomes (1)

• Overall Survival at 100 Days, 1 Year, and 3 Years After Umbilical Cord Blood Transplant in Pediatric Patients.

  To determine the overall survival rate at 1 year after umbilical cord blood transplant in pediatric patients with myeloid hematological malignancies.

  100 days, 1 year, and 3 years

Secondary Outcomes (6)

• Number of Participants With Severe Acute GVHD Grade III-IV

  Day 100

• Number of Participants With Chronic GvHD

  1 year

• Number of Participants With Relapse Rate After Transplant

  1 and 3 years

• Number of Participants With Donor Engraftment After Transplant.

  100 days, 6, 9, 12, 24 and 36 months

• Number of Participants With Platelet Engraftment

  Day 180

Study Arms (1)

Umbilical Cord Blood Transplant

EXPERIMENTAL

Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion

Drug: Busulfan; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Cord Blood Stem Cell Infusion

Interventions

Busulfan DRUG

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.

Also known as: Busulfex

Umbilical Cord Blood Transplant

Cyclophosphamide DRUG

Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg.

Also known as: CTX, Cytoxan

Umbilical Cord Blood Transplant

Fludarabine DRUG

Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients \> 10 kg: 40 mg/m\^2.

Also known as: Fludera

Umbilical Cord Blood Transplant

Cord Blood Stem Cell Infusion PROCEDURE

The cord blood stem cells will be infused on Day 0.

Umbilical Cord Blood Transplant

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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 ≥ 4 x 10\^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.

You may not qualify if:

• 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 \> 3X 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.

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Interventions

Busulfan; Cyclophosphamide; fludarabine

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Caridad A. Martinez
• Organization: Baylor College of Medicine/Texas Children's Hospital

camartin@texaschildrens.org

832-824-4692

Study Officials

• Caridad A Martinez, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Robert A Krance, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Pediatric Hematology/Oncology, Center for Cell and Gene Therapy

Study Record Dates

• First Submitted: November 22, 2010
• First Posted: November 24, 2010
• Study Start: November 1, 2010
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: June 8, 2022
• Results First Posted: June 8, 2022

Record last verified: 2022-05

Locations

US (1)