Clinical Trials /

Myeloablative Umbilical Cord Blood Transplantation in Hematological Diseases

NCT00309842

Description:

RATIONALE: Giving chemotherapy drugs, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells and prepares the patient's bone marrow for the stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil may stop this from happening. PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation works in treating patients who are undergoing an umbilical cord blood transplant for hematologic cancer.

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
  • Lymphoblastic Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Myelofibrosis
  • Non-Hodgkin Lymphoma
  • Plasma Cell Leukemia
  • Prolymphocytic Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Myeloablative Umbilical Cord Blood Transplantation in Hematological Diseases
  • Official Title: Transplantation of Unrelated Umbilical Cord Blood for Patients With Hematological Diseases With Cyclophosphamide/Fludarabine/Total Body Irradiation Myeloablative Preparative Regimen

Clinical Trial IDs

  • ORG STUDY ID: 2005LS043
  • SECONDARY ID: UMN-MT2005-10
  • SECONDARY ID: UMN-0507M71475
  • NCT ID: NCT00309842

Conditions

  • Acute Myeloid Leukemia
  • Acute Lymphocytic Leukemia
  • Chronic Myelogenous Leukemia
  • Myelofibrosis
  • MDS
  • Refractory Anemia
  • Chronic Lymphocytic Leukemia
  • Prolymphocytic Leukemia
  • Non-Hodgkin's Lymphoma
  • Leukemia
  • Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
filgrastimG-CSFUnrelated UCBT for Blood Cancers
cyclophosphamideCytoxanUnrelated UCBT for Blood Cancers
cyclosporineCSAUnrelated UCBT for Blood Cancers
fludarabine phosphateFludaraUnrelated UCBT for Blood Cancers
mycophenolate mofetilMMFUnrelated UCBT for Blood Cancers

Purpose

RATIONALE: Giving chemotherapy drugs, such as fludarabine and cyclophosphamide, and total-body irradiation before a donor umbilical cord blood stem cell transplant helps stop the growth of cancer cells and prepares the patient's bone marrow for the stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil may stop this from happening. PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation works in treating patients who are undergoing an umbilical cord blood transplant for hematologic cancer.

Detailed Description

      OBJECTIVES:

      Primary

        -  Determine the 1-year survival of patients undergoing unrelated umbilical cord blood
           transplantation (UCBT) for hematologic malignancies treated with myeloablative
           preparative regimen comprising fludarabine, cyclophosphamide, and fractionated
           total-body irradiation.

      Secondary

        -  Determine the incidence of transplant-related mortality at 6 months after UCBT.

        -  Evaluate the pattern of chimerism after double UCBT.

        -  Determine the incidence of neutrophil engraftment at day 42 after UCBT.

        -  Determine the incidence of platelet engraftment at 6 months after UCBT.

        -  Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease
           (GVHD) at day 100 after UCBT.

        -  Determine the incidence of chronic GVHD at 1 year after UCBT.

        -  Determine the disease-free survival at 1 and 2 years after UCBT.

        -  Determine the incidence of relapse at 1 year after UCBT.

      OUTLINE: This is a nonrandomized, open-label, multicenter study.

        -  Preparative Regimen: Patients receive fludarabine IV over 1 hour on days -8 to -6 and
           cyclophosphamide IV on days -7 and -6. Patients also undergo total-body irradiation
           twice daily on days -4 to -1.

        -  Umbilical Cord Blood Transplantation (UCBT): Patients undergo 1 or 2 units of UCBT on
           day 0. Patients receive filgrastim (G-CSF) IV once daily beginning on day 1 and
           continuing until blood counts recover.

        -  Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2
           hours 2 or 3 times daily beginning on day -3 and continuing until day 100 followed by a
           taper until day 180. Patients also receive mycophenolate mofetil IV or orally 2 or 3
           times a day beginning on day -3 and continuing until day 30 or 7 days after engraftment
           in the absence of acute GVHD.

      After completion of study treatment, patients are followed periodically for at least 5 years.

      PROJECTED ACCRUAL: A total of 150 patients will be accrued for this study.
    

Trial Arms

NameTypeDescriptionInterventions
Unrelated UCBT for Blood CancersExperimentalPatients undergoing unrelated umbilical cord blood transplantation (UCBT) for hematologic malignancies treated with myeloablative preparative regimen comprising fludarabine phosphate, mycophenolate mofetil, filgrastim, cyclophosphamide, cyclosporine and fractionated total-body irradiation.
  • cyclophosphamide
  • cyclosporine
  • fludarabine phosphate
  • mycophenolate mofetil

Eligibility Criteria

        Inclusion Criteria:

          -  Acute myeloid leukemia (AML): high risk CR1 (as evidenced by preceding myelodysplastic
             syndrome [MDS], high risk cytogenetics, ≥ 2 cycles to obtain complete remission [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 < or = 25% blasts in marrow after having failed one or more
             cycles of chemotherapy. This group of patients will be analyzed separately.

          -  Acute lymphocytic leukemia (ALL): high risk CR1 [t(9;22), t (1:19), t(4;11) or 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 (CML) 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 debulking 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.

          -  Recipients must have a Karnofsky score (adults) ≥ 80 % or Lansky score ≥ 50%
             (pediatrics), and proper organ function.

        Exclusion Criteria

          -  Active infection at time of transplantation

          -  History of human immunodeficiency virus (HIV) infection

          -  Pregnant or breast feeding.

          -  Chemotherapy refractory large cell and high grade NHL

          -  If < or = 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.

          -  Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tostumomab (Bexxar), as
             part of their salvage therapy.
      
Maximum Eligible Age:55 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival
Time Frame:at 1 year
Safety Issue:
Description:Number of patients alive at 1 year after transplant.

Secondary Outcome Measures

Measure:Patients Who Died Due to Transplant
Time Frame:At Month 6
Safety Issue:
Description:Determine the incidence of transplant-related mortality at 6 months after UCBT
Measure:Chimerism
Time Frame:Day 21, Day 100, Month 6, 1 Year, 2 Years
Safety Issue:
Description:Chimerism studies will be performed on the bone marrow on days 21 and 100 and at 6 months, 1 year and 2 years. In cases of slow engraftment a BM biopsy may be repeated on day +28.
Measure:Neutrophil Engraftment
Time Frame:Day 42
Safety Issue:
Description:Determine the incidence of neutrophil engraftment at day 42 after UCBT -Patients diagnosed with graft failure (failure of ANC > 5 x 108/L of donor origin by day +42)
Measure:Platelet Engraftment
Time Frame:1 Year
Safety Issue:
Description:Determine the incidence of platelet engraftment at 6 months after UCBT.
Measure:Acute Graft-Versus-Host Disease
Time Frame:Day 100
Safety Issue:
Description:Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at day 100 after UCBT. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.
Measure:Number of Patients with Chronic Graft-Versus-Host Disease
Time Frame:Year 1
Safety Issue:
Description:Determine the incidence of chronic GVHD at 1 year after UCBT. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Masonic Cancer Center, University of Minnesota

Trial Keywords

  • blastic phase chronic myelogenous leukemia
  • primary myelofibrosis
  • chronic myelomonocytic leukemia
  • myelodysplastic syndromes
  • juvenile myelomonocytic leukemia
  • recurrent adult Burkitt lymphoma
  • recurrent adult immunoblastic large cell lymphoma
  • recurrent lymphoblastic lymphoma
  • recurrent childhood acute myeloid leukemia
  • recurrent childhood large cell lymphoma
  • recurrent follicular lymphoma
  • recurrent marginal zone lymphoma
  • recurrent small lymphocytic lymphoma
  • refractory chronic lymphocytic leukemia
  • refractory multiple myeloma
  • chronic myelogenous leukemia
  • secondary acute myeloid leukemia
  • secondary myelodysplastic syndromes
  • multiple myeloma
  • adult lymphoblastic lymphoma
  • refractory anemia with excess blasts
  • refractory anemia
  • Burkitt lymphoma
  • childhood large cell lymphoma
  • adult Burkitt lymphoma
  • mantle cell lymphoma
  • childhood lymphoblastic lymphoma
  • childhood myelodysplastic syndromes

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