Allogeneic Transplantation for Pediatric Leukemias With Unrelated Donors

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00679536
• Other study ID #: SCT 0208
• Status: Recruiting
• Phase: Phase 1/Phase 2
• First received: May 15, 2008
• Last updated: January 22, 2014
• Start date: May 2008
• Est. completion date: May 2015

Study information

• Verified date: January 2014
• Source: Ann & Robert H Lurie Children's Hospital of Chicago
• Contact: Sonali Chaudhury, MD
• Phone: 312-227-4863
• Email: schaudhury[@]luriechildrens.org
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardThe Robert H. Lurie Comprehensive Cancer Center Of Northwestern University Data Monitoring Committee, USA:
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 21 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia

Intervention

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.
• Fludarabine
Patient will receive Fludarabine from Day -6 to Day -2. The dose of Fludarabine will be 30 mg/m^2/day.
• 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.

Locations

Country	Name	City	State
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Ann & Robert H Lurie Children's Hospital of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	To evaluate the incidence of acute and chronic graft-versus-host disease after hematopoietic stem cell transplant		5 years	Yes