Umbilical Cord Blood Transplantation In Patients With Hematologic Malignancies Using A Myeloablative Preparative Regimen
Condition: Hematologic Malignancies; Disorder Related to Transplantation; Hematopoietic Malignancy
MeSH terms: Neoplasms; Hematologic Neoplasms
Intervention: Preparative Regimen
Intervention description: Fludarabine (75 mg/m2), fractionated total body irradiation (TBI) (12.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at 60mg/kg for two days on day -3 and day -2.
Post-transplantation immunosuppression with cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF will start on day +1.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: Hematologic Malignancies; Umbilical Cord Blood transplantation; Hematopoietic Cell Transplantation

Summary:

      In this study, participants with high-risk hematologic malignancies undergoing hematopoietic
      cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA)-matched
      related/sibling donor (MSD), matched unrelated donor (MURD) or killer-immunoglobulin
      receptors (KIR) ligand mismatched haploidentical donor identified, will receive an umbilical
      cord blood transplantation (UCBT) using a myeloablative preparative regimen.

      The preparative regimen includes fludarabine (75 mg/m2), fractionated total body irradiation
      (TBI) (10.0 Gy), and cyclophosphamide (120mg/kg) with mesna. Fludarabine will be given once a
      day at 25 mg/m2 for three days on day -10 to day -8, TBI will be given twice a day at 150 cGy
      for four days on day -7 to day -4, and cyclophosphamide will be given once a day for at
      60mg/kg for two days on day -3 and day -2. Post-transplantation immunosuppression with
      cyclosporine and MMF will begin on day -3. Cord Blood infusion will occur on day 0 and G-CSF
      will start on day +1.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age less than or equal to 21 years old.

          -  Has a partially HLA-matched single or double UCB product

          -  High-risk hematologic malignancy.

          -  High risk ALL in CR1, ALL in High risk CR2, ALL in CR3 or subsequent.

          -  AML in high risk CR1, AML in CR2 or subsequent

          -  AML in first relapse with < 25% blasts in BM

          -  Therapy related AML, with prior malignancy in CR > 12mo

          -  MDS, primary or secondary

          -  NK cell, biphenotypic, or undifferentiated leukemia in CR1 or subsequent.

          -  CML in accelerated phase, or in chronic phase with persistent molecular positivity or
             intolerance to tyrosine kinase inhibitor.

          -  Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous HCT, or unable
             to mobilize stem cells for autologous HCT.

          -  Non-Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous HCT, or
             unable to mobilize stem cells for autologous HCT.

          -  JMML

          -  All patients with evidence of CNS leukemia must be treated and be in CNS CR to be
             eligible for study.

        Patient must fulfill pre-transplant evaluation:

          -  Cardiac shortening fraction ≥ 26%.

          -  Creatinine clearance ≥ 70 ml/min/1.73m2.

          -  Forced vital capacity (FVC) ≥ 50% of predicted value or pulse oximetry ≥ 92% on room
             air.

          -  Karnofsky (≥ 16 years) or Lansky (<16 years) performance score ≥ 70

          -  Bilirubin ≤ 2.5 mg/dL.

          -  Alanine aminotransferase (ALT) ≤ 5 times the upper limit of normal for age.

          -  Aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age.

        Exclusion Criteria:

          -  Patient has a suitable MSD, volunteer MURD, or KIR mismatched haploidentical donor
             available in the necessary time for stem cell donation.

          -  Patient has any other active malignancy other than the one for which HCT is indicated.

          -  Patient had a prior allogeneic HCT

          -  Patient had an autologous HCT within the previous 12 months.

          -  Patient is pregnant as confirmed by positive serum or urine pregnancy test within 14
             days prior to enrollment.

          -  Patient is lactating

          -  Patient has Down Syndrome

          -  Patient has a current uncontrolled bacterial, fungal, or viral infection per the
             judgment of the PI.