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COMPLETEDPHASE2

Treosulfan/Fludarabine/Low Dose TBI as a Preparative Regimen for Children With AML/MDS Undergoing Allo HCT

A Phase II Study of Treosulfan/Fludarabine/Low Dose Total Body Irradiation as a Preparative Regimen for Children With AML/MDS Undergoing Allogeneic Hematopoietic Cell Transplantation

NCT01772953•Center for International Blood and Marrow Transplant Research

View on ClinicalTrials.gov

Summary

This is a prospective, open-label, nonrandomized, prospective clinical trial evaluating a fixed regimen of treosulfan, fludarabine and low-dose total body irradiation (TBI) in children with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT). The primary hypothesis is that HCT with a preparative regimen consisting of treosulfan, fludarabine and low-dose TBI will result in overall survival (OS) comparable to historical rates observed with conventional myeloablative regimens in the pediatric population. The preparative regimen will result in adequate incidence of neutrophil and platelet engraftment, and acceptable rates of graft-versus-host disease (GVHD), relapse and survival. The pharmacokinetic (PK) profile of treosulfan in children will be comparable to that of adults previously studied.

Detailed Description

The proposed study will evaluate a regimen using treosulfan, fludarabine and low-dose TBI in children and adolescents with AML or MDS undergoing allogeneic HCT. We expect this regimen to yield lower toxicity and at least equivalent rates of disease control and overall survival, compared to current standard myeloablative regimens. The primary objective of this study is to determine the safety and preliminary efficacy of a transplant preparative regimen consisting of treosulfan, fludarabine and low-dose TBI for children with AML and MDS. The primary endpoint will be overall survival (OS) at one year. Secondary objectives to be studied include: pharmacokinetic (PK) profile of treosulfan in children \< 40 kg, non-relapse mortality, disease-free survival, incidences of neutrophil and platelet engraftment, donor chimerism, acute and chronic graft-versus-host disease (GVHD), and relapse.

Eligibility

Age

0 - 21 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Age \< 21 years.
•2. Disease and disease status:
•* Acute myeloid leukemia (AML) in morphologic remission (defined as \< 5% blasts in a bone marrow aspirate of adequate cellularity performed within 28 days from start of conditioning).
•* Myelodysplastic syndrome (MDS): Any 2008 WHO classification subtype (Appendix I). RAEB-2 patients may proceed directly to transplant, but may also be considered for induction chemotherapy before transplant. Patients with ≥20% morphologic marrow blasts will require induction therapy to reduce morphologic marrow blasts below 5% before transplant.
•3. Karnofsky Index or Lansky Play-Performance Scale \> 70 % on pre-transplant evaluation. Karnofsky scores must be used for patients \> 16 years of age and Lansky scores for patients \< 16 years of age.
•4. Able to give informed consent if \> 18 years, or with a legal guardian capable of giving informed consent if \< 18 years.
•5. Negative pregnancy test (serum, urine β-HCG, or other test per institutional guidelines) for females of childbearing potential.
•6. A single previous autologous or allogeneic HCT is allowed as long as the time from first to second transplant hematopoietic cell infusion is no less than 6 months.
•7. With a suitable allogeneic hematopoietic cell donor including, as available:
•* HLA-identical related donor matched for HLA-A, and -B at the serologic level at minimum and -DRB1 at high resolution by molecular typing. A single locus mismatched related donor (7/8 matched) is permitted only if there are no 8/8 matched unrelated donors available.
+21 more criteria

Exclusion Criteria

•1. Pregnant or lactating females are ineligible as many of the medications used in this protocol could be harmful to unborn children and infants.
•2. Patients with HIV or uncontrolled fungal, bacterial or viral infections are excluded. Patients with history of fungal disease during induction therapy may proceed if they have a significant response to antifungal therapy with no or minimal evidence of disease remaining by CT evaluation.
•3. Patients with active CNS leukemia or any other active site of extramedullary disease at the time of enrollment are not permitted. Note: Those with prior history of CNS or extramedullary disease, but with no active disease at the time of pre-transplant workup, are eligible.
•4. Patients undergoing a course of chemotherapy using another investigational drug.
•5. Patients diagnosed with Fanconi Anemia.

Locations (23)

Children's Hospital of Alabama/UAB

Birmingham, Alabama, United States

Phoenix Children's Hospital

Phoenix, Arizona, United States

City of Hope

Duarte, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Children's Hospital of Colorado

Aurora, Colorado, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

All Children's Hospital

St. Petersburg, Florida, United States

Riley Hospital for Children/Indiana University

Indianapolis, Indiana, United States

University of Michigan

Ann Arbor, Michigan, United States

University of Minnesota

Minneapolis, Minnesota, United States

Key Dates

Start Date

September 1, 2013

Primary Completion Date

August 1, 2015

Completion Date

August 1, 2015

Last Updated

October 12, 2016

Enrollment

ACTUAL participants

Conditions

Acute Myeloid Leukemia (AML)Myelodysplastic Syndrome (MDS)

Interventions

Treosulfan

DRUG

Haplo-identical Transplantation for Severe Aplastic Anemia, Hypo-plastic MDS and PNH Using Peripheral Blood Stem Cells and Post-transplant Cyclophosphamide for GVHD Prophylaxis

NCT03520647

Severe Aplastic Anemia (SAA)Hypo-Plastic Myelodysplastic Syndrome (MDS)+1 more

View study

RECRUITINGPHASE2

BCL2i CLAG-M in R/R Acute Myeloid Leukemia

NCT06660368

Relapsed or Refractory Acute Myeloid Leukemia (AML)

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: October 12, 2016Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Treosulfan/Fludarabine/Low Dose TBI as a Preparative Regimen for Children With AML/MDS Undergoing Allo HCT

Inclusion Criteria

Exclusion Criteria

Haplo-identical Transplantation for Severe Aplastic Anemia, Hypo-plastic MDS and PNH Using Peripheral Blood Stem Cells and Post-transplant Cyclophosphamide for GVHD Prophylaxis

BCL2i CLAG-M in R/R Acute Myeloid Leukemia

CLN-049 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

Effect of Moderate Renal Impairment and Race/Ethnicity on Treosulfan Pharmacokinetics

HSCT for Patients With Fanconi Anemia Using Risk-Adjusted Chemotherapy

BAL0891 in Patients With Advanced Solid Tumors or Relapsed or Refractory Acute Myeloid Leukemia