Clinical Trials /

Allogeneic Transplantation for Pediatric Leukemias With Unrelated Donors

NCT00679536

Description:

The study proposes the use of Fludarabine, Busulfan, Anti Thymocyte Globulin Rabbit (ATG) and Total Body Irradiation as a preparative regimen before hematopoietic stem cell transplant from unrelated donor peripheral blood stem cells (PBSC). The hypothesis states that the 100 day mortality after this type of transplant will be significantly below the accepted standards, which is about 30% for unrelated donors.

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

Unknown status

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Allogeneic Transplantation for Pediatric Leukemias With Unrelated Donors
  • Official Title: Allogeneic Transplantation for Pediatric Leukemias With Unrelated Donors Using Fludarabine, Busulfan, 400 cGy Total Body Irradiation, and Thymoglobulin

Clinical Trial IDs

  • ORG STUDY ID: SCT 0208
  • NCT ID: NCT00679536

Conditions

  • Leukemia

Interventions

DrugSynonymsArms
BusulfanIV BusulfexA
FludarabineFludaraA
ThymoglobulinA

Purpose

The study proposes the use of Fludarabine, Busulfan, Anti Thymocyte Globulin Rabbit (ATG) and Total Body Irradiation as a preparative regimen before hematopoietic stem cell transplant from unrelated donor peripheral blood stem cells (PBSC). The hypothesis states that the 100 day mortality after this type of transplant will be significantly below the accepted standards, which is about 30% for unrelated donors.

Detailed Description

      The primary objective of this study is to evaluate the toxicity (as measured as 100 day
      survival) after hematopoietic stem cell transplant from an unrelated donor with a novel
      preparative regimen of Fludarabine, Busulfan, Anti-Thymocyte Globulin, and Total Body
      Irradiation for pediatric patients with leukemia. The secondary objectives are to evaluate
      the relapse-free and overall survival after hematopoietic stem cell transplant as well as to
      evaluate the incidence of acute and chronic graft-versus-host disease after this preparative
      regimen.
    

Trial Arms

NameTypeDescriptionInterventions
AExperimentalAll patients on this trial will receive a conditioning regimen of Busulfan, Fludarabine, Anti-Thymocyte Globulin and Total Body Irradiation (400 cGy)
  • Busulfan
  • Fludarabine
  • Thymoglobulin

Eligibility Criteria

        Inclusion Criteria:

          -  Ages 0-21

          -  AML in one of the following stages:

               -  Having preceding myelodysplasia (MDS)

               -  High Risk cytogenetics

               -  Requiring > 2 cycles chemotherapy to obtain complete remission

               -  High allelic ratio FLT3/ITD+,

               -  Standard risk cytogenetics with positive MRD at end of Induction

               -  Second or greater CR

               -  First relapse with < 25% blasts in bone marrow

               -  With therapy-related AML whose prior malignancy has been in remission for at
                  least 12 months

          -  ALL in one of the following stages:

          -  High risk first remission, defined as:

               -  Ph+ ALL; or,

               -  MLL rearrangement with slow early response [defined as having M2 (5-25% blasts)
                  or M3 (>25% blasts on bone marrow examination on Day 14 of induction therapy)];
                  or,

               -  Hypodiploidy (< 44 chromosomes or DNA index < 0.81); or,

               -  End of induction M3 bone marrow; or,

               -  End of induction M2 marrow or MRD>1% with M2-3 marrow or MRD>1% at Day 42.

               -  High-risk infant ALL defined as age <6 months at diagnosis with MLL (11q23)
                  translocation.

          -  High risk second remission, defined as:

               -  Bone marrow relapse < 36 months from induction; or >36 mths if a matched sibling
                  donor is available

               -  T-lineage relapse at any time; or,

               -  Very early isolated CNS relapse (<18 months from diagnosis); or,

               -  Slow reinduction (M2-3 at Day 28) after relapse at any time. − Any third or
                  subsequent CR.

          -  Biphenotypic or undifferentiated leukemia in any CR or if in first relapse must have <
             25% blasts in bone marrow

          -  MDS at any stage; prior therapies allowed

          -  CML in chronic or accelerated phase; prior therapies allowed

          -  Patient also must have the following organ requirements:

               -  Adequate renal function defined as serum creatinine <2x normal, or creatinine
                  clearance > 40 ml/min/m^2 or 70 ml/min.

               -  Adequate liver function as defined by total bilirubin less than or equal to 2
                  times normal and AST and ALT less than or equal to 4 times normal.

               -  Adequate cardiac function as defined by: shortening fraction > 24% by
                  echocardiogram, or ejection fraction > 30% by radionuclide angiogram.

               -  Adequate pulmonary function as defined by DLCO, FEV1/FVC > 60% by pulmonary
                  function tests. For children who are uncooperative for PFTs and have no evidence
                  of dyspnea at rest or exercise intolerance, pulse oximetry > 94% on room air is
                  considered acceptable, with a normal chest xray.

               -  Adequate venous access; a double lumen central vascular access device or its
                  equivalent and an additional PICC line will be required for all patients.

          -  Women of childbearing potential and sexually active males should use effective
             contraception while on study.

        Exclusion Criteria:

          -  Inability to give informed consent or assent

          -  Inability to obtain a suitable donor

          -  Patient who is HIV-positive

          -  Patient who has active Hepatitis B

          -  Patient who is pregnant

          -  Patient who is otherwise considered unsuitable for transplant at the discretion of the
             principal investigator.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:N/A
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To evaluate the toxicity (as measures by 100 day survival) after hematopoietic stem cell transplant from an unrelated donor with a novel preparative regimen.
Time Frame:100 day mortality
Safety Issue:
Description:

Secondary Outcome Measures

Measure:To evaluate the relapse-free and overall survival after hematopoietic stem cell transplant with Fludarabine/Busulfan/ATG/TBI preparative regimen for pediatric patients with leukemia.
Time Frame:5 years
Safety Issue:
Description:
Measure:To evaluate the incidence of acute and chronic graft-versus-host disease after hematopoietic stem cell transplant
Time Frame:5 years
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Unknown status
Lead Sponsor:Ann & Robert H Lurie Children's Hospital of Chicago

Trial Keywords

  • Reduced Toxicity
  • Toxicity
  • Event Free Survival
  • Graft vs Host Disease

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