Clinical Trials /

Hematopoietic Stem Cell Transplantation in the Treatment of Infant Leukemia

NCT00357565

Description:

RATIONALE: Giving chemotherapy, such as busulfan, fludarabine, and melphalan, before a donor umbilical cord blood stem cell transplant helps stop the growth of abnormal or 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 combination chemotherapy followed by a donor umbilical cord blood transplant works in treating infants with high-risk acute leukemia or myelodysplastic syndromes.

Related Conditions:
  • Acute Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Hematopoietic Stem Cell Transplantation in the Treatment of Infant Leukemia
  • Official Title: Hematopoietic Cell Transplantation in the Treatment of Infant Leukemia and Myelodysplastic Syndrome

Clinical Trial IDs

  • ORG STUDY ID: 2005LS075
  • SECONDARY ID: UMN-MT2005-25
  • SECONDARY ID: UMN-0511M77206
  • NCT ID: NCT00357565

Conditions

  • Leukemia
  • Myelodysplastic Syndromes
  • Childhood Acute Myeloid Leukemia in Remission
  • Recurrent Childhood Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
  • Childhood Acute Lymphoblastic Leukemia in Remission
  • Previously Treated Myelodysplastic Syndrome
  • Secondary Myelodysplastic Syndrome
  • Refractory Anemia With Excess Blasts in Transformation
  • Refractory Anemia With Excess Blasts
  • Refractory Anemia
  • De Novo Myelodysplastic Syndrome
  • Childhood Myelodysplastic Syndrome

Interventions

DrugSynonymsArms
filgrastimG-CSFDouble Unit UCB Transplantation
busulfanBusulfexDouble Unit UCB Transplantation
cyclosporineCSADouble Unit UCB Transplantation
fludarabine phosphateFludaraDouble Unit UCB Transplantation
melphalanAlkeranDouble Unit UCB Transplantation
mycophenolate mofetilMMFDouble Unit UCB Transplantation

Purpose

RATIONALE: Giving chemotherapy, such as busulfan, fludarabine, and melphalan, before a donor umbilical cord blood stem cell transplant helps stop the growth of abnormal or 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 combination chemotherapy followed by a donor umbilical cord blood transplant works in treating infants with high-risk acute leukemia or myelodysplastic syndromes.

Detailed Description

      OBJECTIVES:

      Primary

        -  Determine the incidence of engraftment, defined as achieving donor-derived neutrophil
           count > 500/mm³ by day 42, in infants with high-risk acute myeloid leukemia, acute
           lymphoblastic leukemia, or myelodysplastic syndromes treated with a non-irradiation
           containing myeloablative conditioning regimen comprising busulfan, fludarabine, and
           melphalan followed by double umbilical cord blood transplantation (UCBT) with two
           partially HLA-matched units.

      Secondary Objectives

        -  Determine the incidence of transplant-related mortality (TRM) at 6 months after UCBT

        -  Evaluate pattern of chimerism after double UCBT

        -  Determine the incidence of platelet engraftment at 1 year after UCBT

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

        -  Evaluate the developmental outcome after UCBT

      Transplant Related Objectives

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

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

        -  Determine the incidence relapse at 1 and 2 years after UCBT
    

Trial Arms

NameTypeDescriptionInterventions
Double Unit UCB TransplantationExperimentalPatients that receive 2 units of umbilical cord blood transplantation (UCBT).
  • busulfan
  • cyclosporine
  • fludarabine phosphate
  • melphalan
  • mycophenolate mofetil
Single Unit UCB TransplantationExperimentalPatients that receive one unit of umbilical cord blood transplantation (only if 2 adequate size and matched units are not available).
  • busulfan
  • cyclosporine
  • fludarabine phosphate
  • melphalan
  • mycophenolate mofetil

Eligibility Criteria

        Inclusion Criteria:

          -  Matched sibling donor (HLA 8/8), if available, or a unrelated partially HLA matched
             single unit based on the following priority:

               -  1st priority: 4/6 matched unit, cell dose >5 x 10-7 nucleated cells/kg

               -  2nd priority: 5/6 matched unit, cell dose > 4 x 10-7 nucleated cells/kg

               -  3rd priority: 6/6 matched unit, cell dose > 3 x 10-7 nucleated cells/kg

          -  Patients aged ≤ 3 years at diagnosis (not age of transplant) with hematological
             malignancy as detailed below:

               -  Acute myeloid leukemia: high risk CR1 as evidenced by:

                    -  High risk cytogenetics t(4;11) or other MLL rearrangements; chromosome 5, 7,
                       or 19 abnormalities; complex karyotype (>5 distinct changes); ≥ 2 cycles to
                       obtain complete response (CR); CR2 or higher; Preceding myelodysplastic
                       syndrome (MDS); All patients must be in CR or early relapse (i.e., <15%
                       blasts in BM).

                    -  Acute lymphocytic leukemia: high risk CR1 as evidenced by: High-risk
                       cytogenetic: t(4;11) or other MLL rearrangements; hypodiploid; t(9;22); >1
                       cycle to obtain CR; CR2 or higher; 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%.

               -  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.

               -  Persistent or rising minimal residual disease (MRD) after standard chemotherapy
                  regimens: Patients with evidence of minimal residual disease at the completion of
                  therapy or evidence of rising MRD while on therapy. MRD will be defined by either
                  flow cytometry (>0.1% residual cells in the blast gate with immune phenotype of
                  original leukemic clone), by molecular techniques (PCR or FISH) or conventional
                  cytogenetics (g-banding).

               -  New Leukemia Subtypes: A major effort in the field of pediatric hematology is to
                  identify patients who are of high risk for treatment failure so that patients can
                  be appropriately stratified to either more (or less) intensive therapy. This
                  effort is continually ongoing and retrospective studies identify new disease
                  features or characteristics that are associated with treatment outcomes.
                  Therefore, if new high risk features are identified after the writing of this
                  protocol, patients can be enrolled with the approval of two members of the study
                  committee.

          -  Recipients must have a Lansky score ≥ 50% and have acceptable organ function defined
             as:

               -  Renal: glomerial filtration rate > 60ml/min/1.73m^2

               -  Hepatic: bilirubin, AST/ALT, ALP < 5 x upper limit of normal,

               -  Pulmonary function: oxygen saturation >92%

               -  Cardiac: left ventricular ejection fraction > 45%.

          -  Voluntary written informed consent before performance of any study-related procedure
             not part of normal medical care.

        Exclusion Criteria:

          -  Active infection at time of transplantation (including active infection with
             Aspergillus or other mold within 30 days).

          -  History of HIV infection or known positive serology

          -  Myeloablative transplant within the last 6 months.

          -  Evidence of active extramedullary disease (including central nervous system leukemia).
      
Maximum Eligible Age:3 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Engraftment
Time Frame:Day 42 After Transplant
Safety Issue:
Description:Defined as achieving donor derived neutrophil count >500/uL by day 42 in young children with leukemia or myelodysplastic syndrome undergoing a partially matched single unit umbilical cord blood transplant (UCBT) after a myeloablative preparative regimen consisting of busulfan, melphalan and fludarabine.

Secondary Outcome Measures

Measure:Incidence of transplant-related mortality (TRM)
Time Frame:at 6 months after transplant
Safety Issue:
Description:defined as death due to transplant
Measure:Incidence of platelet engraftment
Time Frame:at 1 year after transplant
Safety Issue:
Description:defined as platelet count > 50,000
Measure:Incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV
Time Frame:Day 100 After Transplant
Safety Issue:
Description:Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack.
Measure:Incidence of chronic graft-versus-host disease (GVHD)
Time Frame:1 Year After Transplant
Safety Issue:
Description:Graft-versus-host disease (GVHD) is a common complication of allogeneic bone marrow transplantation in which functional immune cells in the transplanted marrow recognize the recipient as "foreign" and mount an immunologic attack.
Measure:Incidence of relapse
Time Frame:1 and 2 years after transplant
Safety Issue:
Description:defined using standard criteria (bone marrow blast count and cytogenetics).
Measure:Overall survival
Time Frame:at 1 and 2 years after transplant
Safety Issue:
Description:Alive after transplant.
Measure:Developmental Outcomes
Time Frame:at 1, 2, and 5 years after transplant
Safety Issue:
Description:Neuropsychological evaluation to assess baseline neurocognitive, adaptive, and behavioral functioning and presence of developmental delays
Measure:Disease-free survival
Time Frame:at 1 and 2 years after transplant
Safety Issue:
Description:defined as patients who are alive and in hematological remission.

Details

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

Trial Keywords

  • MDS
  • AML

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