Clinical Trials /

Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for Hematological Diseases

NCT01962636

Description:

This is a treatment guideline for an unrelated umbilical cord blood transplant (UCBT) using a myeloablative preparative regimen for the treatment of hematological diseases, including, but not limited to acute leukemias. The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI).

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Anaplastic Large Cell Lymphoma
  • Burkitt Lymphoma
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Chronic Myeloid Leukemia
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Myeloproliferative Neoplasm
  • Non-Hodgkin Lymphoma
  • Plasma Cell Leukemia
  • Prolymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for Hematological Diseases
  • Official Title: Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for the Treatment of Hematological Diseases

Clinical Trial IDs

  • ORG STUDY ID: 2013OC013
  • NCT ID: NCT01962636

Conditions

  • Acute Myeloid Leukemia (AML)
  • Acute Lymphocytic Leukemia (ALL)
  • Chronic Myelogenous Leukemia
  • Plasma Cell Leukemia
  • Myelofibrosis
  • Myelodysplasia
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Marginal Zone B-Cell Lymphoma
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle-Cell Lymphoma
  • Prolymphocytic Leukemia
  • Diffuse Large B Cell Lymphoma
  • Lymphoblastic Lymphoma
  • Burkitt's Lymphoma
  • Non-Hodgkin Lymphoma
  • Multiple Myeloma

Interventions

DrugSynonymsArms
FludarabineFludaraUmbilical Cord Blood Transplant
CyclophosphamideCytoxanUmbilical Cord Blood Transplant
Cyclosporine ACSAUmbilical Cord Blood Transplant
Mycophenylate mofetilMMFUmbilical Cord Blood Transplant
Umbilical cord bloodUCBUmbilical Cord Blood Transplant

Purpose

This is a treatment guideline for an unrelated umbilical cord blood transplant (UCBT) using a myeloablative preparative regimen for the treatment of hematological diseases, including, but not limited to acute leukemias. The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI).

Detailed Description

      This is a study to collect routine clinical data from UCBT using unrelated single or double
      UCB units as an alternative, non-HLA-matched stem cell source for patients with hematological
      diseases.

        -  data collection from transplant preparative therapy consisting of treatments with
           chemotherapeutic regimens and total body irradiation.

        -  data collection from umbilical cord blood selection and infusion.

        -  data collection from standard supportive disease and transplant related care.

      Pre- and post-transplant medication, UCB selection and infusion, supportive care, and
      follow-up will be according to the current University of Minnesota BMT guidelines.

      An average of 18 patients are expected to be treated on this protocol per year.
    

Trial Arms

NameTypeDescriptionInterventions
Umbilical Cord Blood TransplantExperimentalThe myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI)followed by umbilical cord blood transplant. Immunosuppressive Cyclosporine and Mycophenylate Mofetil (MMF) will be administered pre- and post UCBT.
  • Fludarabine
  • Cyclophosphamide
  • Cyclosporine A
  • Mycophenylate mofetil

Eligibility Criteria

        Inclusion Criteria:

          -  Eligible Disease Status

               -  Acute Myeloid Leukemia (AML): high risk CR1 (as evidenced by preceding MDS, high
                  risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic
                  leukemia; CR2+. All patients must be in CR as defined by hematological recovery,
                  AND <5% blasts by light microscopy within the bone marrow with a cellularity of
                  ≥15%.

               -  Very high risk pediatric patients with AML: Patients <21 years, however, are
                  eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or
                  more cycles of chemotherapy.

               -  Acute Lymphocytic Leukemia (ALL): high risk CR1 as defined by cytogenetics (such
                  as t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1
                  abnormalities), DNA index < 0.81, > 1 cycle to obtain CR or presence minimal
                  residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR
                  as defined by hematological recovery, AND <5% blasts by light microscopy within
                  the bone marrow with a cellularity of ≥15%.

               -  Very high risk pediatric patients with ALL: patients <21 years are also
                  considered high risk CR1 if they had M2 or M3 marrow at day 42 from the
                  initiation of induction or M3 marrow at the end of induction. They are eligible
                  once they achieved a complete remission.

               -  Chronic Myelogenous Leukemia excluding refractory blast crisis: To be eligible in
                  first chronic phase (CP1) patient must have failed or be intolerant to imatinib
                  mesylate.

               -  Plasma Cell Leukemia after initial therapy, who achieved at least a partial
                  remission

               -  Advanced Myelofibrosis

               -  Myelodysplasia (MDS) IPSS INT-2 or High Risk (i.e. RAEB, RAEBt) or Refractory
                  Anemia with severe pancytopenia or high risk cytogenetics: Blasts must be < 10%
                  by a representative bone marrow aspirate morphology.

               -  Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone
                  B-Cell Lymphoma or Follicular Lymphoma are eligible if there was disease
                  progression/relapse within 12 of achieving a partial or complete remission.
                  Patients who had remissions lasting > 12 months, are eligible after at least two
                  prior therapies. Patients with bulky disease (nodal mass greater than 5 cm)
                  should be considered for de-bulking chemotherapy before transplant.

               -  Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are
                  eligible after initial therapy in CR1+ or PR1+.

               -  Large Cell NHL > CR2/> PR2: Patients in CR2/PR2 with initial short remission (<6
                  months) are eligible.

               -  Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after
                  initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II < 1
                  year.

               -  Multiple Myeloma beyond PR2: Patients with chromosome 13 abnormalities, first
                  response lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be
                  considered for this protocol after initial therapy.

               -  Myeloproliferative Syndromes

          -  Availability of suitable UCB unit(s)

          -  0 to 55 years

          -  Voluntary written consent (adult or parental/guardian)

        Exclusion Criteria:

          -  previous irradiation that precludes the safe administration of TBI - Radiation
             Oncology will evaluate all patients who have had previous radiation therapy

          -  chemotherapy refractory large cell and high grade NHL (ie progressive disease after >
             2 salvage regimens)

          -  if ≤ 18 years old, prior myeloablative transplant within the last 6 months. If >18
             years old prior myeloablative allotransplant or autologous transplant

          -  extensive prior therapy including > 12 months alkylator therapy or > 6 months
             alkylator therapy with extensive radiation

          -  pregnant or breastfeeding

          -  HIV positive
      
Maximum Eligible Age:55 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Survival at 1 year post-transplant
Time Frame:1 year
Safety Issue:
Description:The number of patients that are still living 1 year after UCBT.

Secondary Outcome Measures

Measure:Incidence of neutrophil engraftment at day 42.
Time Frame:42 days
Safety Issue:
Description:Number of subjects with neutrophil engraftment at day 42 post UCBT.
Measure:Platelet engraftment at 1 year.
Time Frame:1 year
Safety Issue:
Description:Number of patients with platelet engraftment at 1 year post UCBT.
Measure:Pattern of chimerism after transplant.
Time Frame:1 year
Safety Issue:
Description:Pattern of chimerism after transplant. Chimerism will be plotted with box-plots and described over time.
Measure:Incidence of graft failure.
Time Frame:100 days
Safety Issue:
Description:Cumulative incidence of graft failure after UCBT.
Measure:Incidence of acute graft versus host disease at 100 days.
Time Frame:100 days
Safety Issue:
Description:Cumulative incidence will be used to estimate acute graft versus host disease 100 days after UCBT.
Measure:Incidence of chronic graft versus host disease at 1 year.
Time Frame:1 year
Safety Issue:
Description:Cumulative incidence will be used to estimate chronic GVHD at 1 year post UCBT.
Measure:Incidence of transplant related mortality at 6 months.
Time Frame:6 months
Safety Issue:
Description:Cumulative incidence will be used to estimate transplant related mortality at 6 months post UCBT.
Measure:Incidence of disease free survival
Time Frame:1, 2 years
Safety Issue:
Description:Kaplan-Meier curves will be used to estimate disease-free survival at 1 and 2 years post UCBT.
Measure:Incidence of overall survival.
Time Frame:1, 2 years
Safety Issue:
Description:Kaplan-Meier curves will be used to estimate overall survival at 1 and 2 years post UCBT.

Details

Phase:N/A
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Masonic Cancer Center, University of Minnesota

Trial Keywords

  • Umbilical Cord Transplant
  • Acute Myeloid Leukemia (AML)
  • Acute Lymphocytic Leukemia (ALL)
  • Chronic Myelogenous Leukemia
  • Plasma Cell Leukemia
  • Myelofibrosis
  • Myelodysplasia
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Marginal Zone B-Cell Lymphoma
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle-Cell Lymphoma
  • Prolymphocytic Leukemia
  • Large Cell Non-Hodgkin Lymphoma
  • Lymphoblastic Lymphoma
  • Burkitt's Lymphoma
  • Non-Hodgkin Lymphoma
  • Multiple Myeloma

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