Have you or your loved ones been diagnosed with childhood acute lymphoblastic leukemia in remission?

You may be eligible to participate in a childhood acute lymphoblastic leukemia in remission clinical trial.

Have you or your loved ones been diagnosed with childhood acute lymphoblastic leukemia in remission? You may be eligible to participate in a childhood acute lymphoblastic leukemia in remission clinical trial.

What is a clinical trial? Is participating in a clinical trial right for you? Learn more

Childhood Acute Lymphoblastic Leukemia in Remission Clinical Trial in Minneapolis MN

NCT00357565 | Phase 2 | Interventional

Have you or your loved ones been diagnosed with childhood acute lymphoblastic leukemia in remission?

You may be eligible to participate in a childhood acute lymphoblastic leukemia in remission clinical trial.

Recruiting

Male & Female

Up to 3

Years old

This study is looking to recruit 20 Participants

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.

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Details for the study

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

Brief Summary

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

Treatments and/or Procedures

Filgrastim

All patients will receive G-CSF 5 mcg/kg/day intravenous (IV) (dose rounded to vial size) based on the actual body weight IV beginning on day +1 after umbilical cord blood (UCB) infusion. G-CSF will be administered daily until the absolute neutrophil count (ANC) exceeds 2.5 x 10^9/L for three consecutive days and then discontinued. If the ANC decreases to <1.0 x 10^9/L, G-CSF will be reinstituted.

Cyclosporine

Patients will receive cyclosporine (CSA) therapy beginning on day -3 maintaining a level of >200 ng/mL. For children < 40 kg the initial dose will be 2.5 mg/kg intravenous (IV) over 2 hours every 8 hours.

Fludarabine phosphate

Administered 25 mg/m^2 intravenous (IV) over 60 minutes on Days -4 through -2.

Mycophenolate mofetil

All patients will begin mycophenolate mofetil (MMF) on day -3. Patients <45 kilograms will receive MMF at the dose of 15 mg/kg/dose every 8 hours (max dose 1gm/dose) orally or intravenously (PO or IV).

Melphalan

Administered 60 mg/m^2 intravenous (IV) over 30 minutes on Days -4 through -2.

Busulfan

Administered 1.1 mg/kg if <12 kg intravenous (IV) every 6 hours (0.8 mg/kg if >12 kg IV every 6 hours on Days -8 through -5.

Umbilical cord blood transplantation

The product is infused via IV drip directly into the central line without a needle, pump or filter on Day 0.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.

Primary

Incidence of Engraftment

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.

Day 42 After Transplant

Secondary

Incidence of acute graft-versus-host disease (GVHD) grade II-IV and grade III-IV

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.

Day 100 After Transplant

Secondary

Incidence of chronic graft-versus-host disease (GVHD)

1 Year After Transplant

Secondary

Overall survival

Alive after transplant.

at 1 and 2 years after transplant

Secondary

Developmental Outcomes

Neuropsychological evaluation to assess baseline neurocognitive, adaptive, and behavioral functioning and presence of developmental delays

at 1, 2, and 5 years after transplant

Secondary

Disease-free survival

defined as patients who are alive and in hematological remission.

at 1 and 2 years after transplant

Secondary

Incidence of transplant-related mortality (TRM)

defined as death due to transplant

at 6 months after transplant

Secondary

Incidence of platelet engraftment

defined as platelet count > 50,000

at 1 year after transplant

Secondary

Incidence of relapse

defined using standard criteria (bone marrow blast count and cytogenetics).

1 and 2 years after transplant

Study 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).