Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies

• Status: Active, not recruiting
• Trial end date: 2027-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Baylor College of Medicine
• Collaborators: Center for Cell and Gene Therapy, Baylor College of Medicine; Texas Children's Hospital
• Treatments: Busulfan; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Vidarabine

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 ≥ 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.

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 > 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.