Allogeneic Transplantation for Pediatric Leukemias With Unrelated Donors

Allogeneic Transplantation for Pediatric Leukemias With Unrelated Donors Using Fludarabine, Busulfan, 400 cGy Total Body Irradiation, and Thymoglobulin

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.

Study Overview

• Status: Unknown
• Conditions: Leukemia
• Intervention / Treatment: Drug: Busulfan; Drug: Fludarabine; Drug: Thymoglobulin; Radiation: Total Body Irradiation

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.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Ann & Robert H. Lurie Children's Hospital of Chicago
      • Contact: Sonali Chaudhury, MD; Phone Number: 312-227-4863; Email: schaudhury@luriechildrens.org
      • Contact: Colleen E Rosen, BS, RN; Phone Number: 312-227-4870; Email: crosen@luriechildrens.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: A; All patients on this trial will receive a conditioning regimen of Busulfan, Fludarabine, Anti-Thymocyte Globulin and Total Body Irradiation (400 cGy)

Drug: Busulfan; Patient will receive a Test Dose of Busulfan on either Day -10 or Day -9. Patient will receive their Regimen Dose of Busulfan on Day -5 to Day -2. The regimen dose of Busulfan will be based off of the findings from their Test Dose.; Other Names: IV Busulfex; Drug: Fludarabine; Patient will receive Fludarabine from Day -6 to Day -2. The dose of Fludarabine will be 30 mg/m^2/day.; Other Names: Fludara; Drug: Thymoglobulin; The patient will also receive Thymoglobulin (rabbitATG) on Day -4 to Day -2. Each dose of rabbitATG will be 1.5 mg/kg/day.; Radiation: Total Body Irradiation; On Day -1 the patient will receive a total of 400 cGy of Total Body Irradiation.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
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.	5 years
To evaluate the incidence of acute and chronic graft-versus-host disease after hematopoietic stem cell transplant	5 years

Collaborators and Investigators

• Sponsor: Ann & Robert H Lurie Children's Hospital of Chicago
• Investigators: Principal Investigator: Sonali Chaudhury, MD, Ann & Robert H Lurie Children's Hospital of Chicago

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (ANTICIPATED): May 1, 2015
• Study Completion (ANTICIPATED): May 1, 2015

Study Registration Dates

• First Submitted: May 15, 2008
• First Submitted That Met QC Criteria: May 16, 2008
• First Posted (ESTIMATE): May 19, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): January 23, 2014
• Last Update Submitted That Met QC Criteria: January 22, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: Toxicity; Graft vs Host Disease; Event Free Survival; Reduced Toxicity
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Fludarabine; Busulfan; Thymoglobulin
• Other Study ID Numbers: SCT 0208