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Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

Information source: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

Intervention: treosulfan (Drug); fludarabine phosphate (Drug); total-body irradiation (Radiation); peripheral blood stem cell transplantation (Procedure); tacrolimus (Drug); allogeneic bone marrow transplantation (Procedure); allogeneic hematopoietic stem cell transplantation (Procedure); methotrexate (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Fred Hutchinson Cancer Research Center

Official(s) and/or principal investigator(s):
Boglarka Gyurkocza, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


This phase II trial is studying how well giving treosulfan together with fludarabine phosphate and total-body irradiation followed by donor stem cell transplant works in treating patients with high-risk acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia. Giving chemotherapy, such as treosulfan and fludarabine phosphate, and total-body irradiation before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and methotrexate before and after transplant may stop this from happening

Clinical Details

Official title: A Multi-Center Study of Conditioning With Treosulfan, Fludarabine and Escalating Doses of TBI for Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia (AML) Myelodysplastic Syndrome (MDS), and Acute Lymphoblastic Leukemia (ALL)

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Relapse incidence to < 15%

Non relapse mortality incidence

Detailed description: PRIMARY OBJECTIVES: I. Decrease the incidence of relapse to < 15% at 6 month post transplant in patients with high risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) transplanted from related or unrelated donors, without unacceptably increasing toxicity (10% non-relapse mortality [NRM] at 6 months). SECONDARY OBJECTIVES: I. Evaluate the incidence of NRM at 180 days and 1 year after hematopoietic cell transplantation (HCT). II. Evaluate overall survival (OS) and relapse-free survival (RFS). III. Incidence of grades II-IV acute graft-versus-host disease (GVHD). IV. Incidence of chronic GVHD. V. Donor chimerism on days +28 and +100. OUTLINE: CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) over 30

minutes on days - 6 to day -2 and treosulfan IV over 2 hours on days -6 to day -4. Patients

also undergo total-body irradiation on day 0. TRANSPLANTATION: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0. GVHD PROPHYLAXIS: Patients receive tacrolimus IV continuously or orally (PO) twice daily

(BID) on days - 1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients

also receive methotrexate IV on days 1, 3, 6, and 11. After completion of study treatment, patients are followed up periodically.


Minimum age: N/A. Maximum age: 60 Years. Gender(s): Both.


Inclusion Criteria:

- Acute myeloid leukemia (AML):

- All AML patients beyond 1st remission;

- Intermediate or high risk AML patients (based on South West Oncology Group

[SWOG] cytogenetic criteria) in 1st complete remission

- Myelodysplastic syndrome (MDS)

- Other myeloid malignancies as chronic myelogenous leukemia (CML), CML accelerated

phase, CML blast crisis, chronic myelomonocytic leukemia (CMML) (to be approved by patient care conference [PCC])

- With Karnofsky Index or Lansky Play-Performance Scale > 70% on pre-transplant


- Able to give informed consent (if > 18 years), or with a legal guardian capable of

giving informed consent (if < 18 years)

- Previous autologous or allogeneic HCT is allowed

- Donors must be:

- Human leukocyte antigen (HLA)-identical related donors or

- Unrelated donors matched for HLA-A, B, C, DRB1, and DQB1 defined by high

resolution deoxyribonucleic acid (DNA) typing or mismatched for one HLA allele, except for HLA-C where no mismatch is allowed

- Able to undergo peripheral blood stem cell collection or bone marrow harvest

- In good general health, with a Karnofsky or Lansky Play Performance score > 90%

- Able to give informed consent (if > 18 years), or with a legal guardian capable

of giving informed consent (if < 18 years)

- Acute lymphoblastic leukemia (ALL): all ALL patients not eligible for other protocols

Exclusion Criteria:

- Receiving umbilical cord blood

- With impaired cardiac function as evidenced by ejection fraction < 35% or cardiac

insufficiency requiring treatment or symptomatic coronary artery disease

- With impaired pulmonary function as evidenced by partial pressure of oxygen (pO2) <

70 mm Hg and diffusing capacity of the lung for carbon monoxide (DLCO) < 70% of predicted or pO2 < 80 mm Hg and DLCO < 60% of predicted; or receiving supplementary continuous oxygen

- With impaired renal function as evidenced by creatinine-clearance < 50% for age,

weight, height or serum creatinine > 2x upper normal limit or dialysis-dependent

- With hepatic dysfunction as evidenced by total bilirubin or aspartate

aminotransferase (AST) or alanine aminotransferase (ALT) > 2. 0 x upper normal limit or evidence of synthetic dysfunction or severe cirrhosis

- With active infectious disease requiring deferral of conditioning, as recommended by

an Infectious Disease specialist

- With human immunodeficiency virus (HIV)-positivity or active infectious hepatitis

because of possible risk of lethal infection when treated with immunosuppressive therapy

- With central nervous system (CNS) leukemic involvement not clearing with intrathecal

chemotherapy and/or cranial radiation prior to initiating conditioning (day - 6)

- With life expectancy severely limited by diseases other than malignancy

- Women who are pregnant or lactating because of possible risk to the fetus or infant

- With known hypersensitivity to treosulfan and/or fludarabine

- Receiving another experimental drug within 4 weeks before initiation of conditioning

(day - 6)

- Unable to give informed consent (if > 18 years) or with a legal guardian (if < 18

years) unable to give informed consent

- Ineligible donors will be those:

- Deemed unable to undergo marrow harvesting or PBSC mobilization and


- Who are HIV-positive

- With active infectious hepatitis

- Females with a positive pregnancy test

- Unable to give informed consent (if > 18 years) or with a legal guardian (if <

18 years) unable to give informed consent

Locations and Contacts

University of Colorado, Denver, Colorado 80217-3364, United States

Oregon Health and Science University, Portland, Oregon 97239, United States

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, Seattle, Washington 98109, United States

Additional Information

Starting date: February 2009
Last updated: October 29, 2013

Page last updated: August 20, 2015

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