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A Study of a Reduced-Intensity Conditioning Regimen With Treosulfan and Fludarabine for Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Leukemia

Phase 1/Phase 2
60 Years
Not Enrolling
Leukemia, Myelodysplastic Syndromes

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Trial Information

A Study of a Reduced-Intensity Conditioning Regimen With Treosulfan and Fludarabine for Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Leukemia


Primary Phase

- Determine the best dose of treosulfan when administered with fludarabine as a
reduced-intensity conditioning regimen followed by allogeneic hematopoietic stem cell
transplantation, in terms of incidence of severe to fatal toxicity to major organ
systems and incidence of graft failure, in patients with acute myeloid leukemia,
lymphoblastic leukemia, or myelodysplastic syndrome.

Secondary Phase

- Determine the safety of this regimen, in terms of incidence of grade II-IV acute and
chronic graft-versus-host disease, in these patients.

- Determine, preliminarily, the efficacy of this regimen, in terms of incidence of
relapse, overall and disease-free survival, donor chimerism on days 28 and 100, and
incidence of 200-day and 1-year nonrelapse mortality, in these patients.

- Determine the pharmacokinetic and pharmacodynamic profile of treosulfan in patients
treated with this regimen.

OUTLINE: This is a multicenter, dose-finding study of treosulfan.

- Reduced-intensity conditioning: Patients receive treosulfan IV over 2 hours on days -6
to -4 and fludarabine IV over 30 minutes on days -6 to -2.

Cohorts of 5-10 patients receive escalating/de-escalating doses of treosulfan until the best
dose is determined among the 3 pre-selected doses. The best dose is defined as the dose
preceding that at which 4 of 10 patients experience dose-limiting toxicity.

- Allogeneic hematopoietic cell transplantation (AHCT): Patients undergo allogeneic bone
marrow or peripheral blood stem cell transplantation on day 0.

All male patients with acute lymphoblastic leukemia OR male patients with acute myeloid
leukemia who have prior or current testicular involvement receive external-beam radiotherapy
to the testicles before AHCT.

After completion of study treatment, patents are followed periodically.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Inclusion Criteria


- Diagnosis of acute myeloid leukemia, lymphoblastic leukemia, or myelodysplastic

- Any phase allowed, including any of the following:

- Disease in remission

- Relapsed or primary refractory disease

- No CNS leukemic involvement not clearing with prior intrathecal chemotherapy and/or
cranial radiotherapy

- Planning to undergo unmanipulated allogeneic bone marrow or peripheral blood stem
cell transplantation

- Filgrastim (G-CSF) mobilization of bone marrow or stem cells allowed

- Donor available, meeting 1 of the following criteria:

- HLA-identical related donor

- HLA-A, -B, -C, -DRB1, and -DQB1 matched unrelated donor by high-resolution DNA

- A single allele mismatch allowed


Performance status

- Karnofsky 70-100% OR

- Lansky 70-100%

Life expectancy

- Not specified


- Not specified


- Bilirubin ≤ 2 times upper limit of normal (ULN)

- AST ≤ 2 times ULN

- No evidence of synthetic dysfunction

- No severe cirrhosis

- No active infectious hepatitis


- Creatinine clearance ≥ 50%

- Creatinine ≤ 2 times ULN

- Dialysis independent


- No cardiac insufficiency requiring treatment

- No symptomatic coronary artery disease

- Ejection fraction ≥ 35% (for patients with history of cardiac disease or
anthracycline exposure)


- PO_2 ≥ 70 mm Hg AND DLCO ≥ 70% of predicted OR

- PO_2 ≥ 80 mm Hg AND DLCO ≥ 60% of predicted

- Not requiring supplementary continuous oxygen


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other disease that would severely limit life expectancy

- No HIV positivity

- No active infection requiring deferral of conditioning

- No known hypersensitivity to the study drugs


Biologic therapy

- See Disease Characteristics

- No prior allogeneic bone marrow or stem cell transplantation

- No concurrent umbilical cord blood or autologous transplantation


- See Disease Characteristics


- See Disease Characteristics


- More than 4 weeks since prior experimental drugs

- Concurrent enrollment on another protocol for graft-versus-host disease prophylaxis

Type of Study:


Study Design:

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

Outcome Measure:

Number of Patients Experiencing Regimen-related Toxicity Events in Study Population

Outcome Description:

Proportion of patients experiencing regimen-related toxicity to major organ systems from day minus 6 to day 28. Major organ systems: cardiac, bladder/renal, pulmonary, hepatic, neurologic and gastrointestinal

Outcome Time Frame:

34 days and 2 years

Safety Issue:


Principal Investigator

Eneida Nemecek, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

OHSU Knight Cancer Institute


United States: Food and Drug Administration

Study ID:




Start Date:

June 2005

Completion Date:

October 2009

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • adult acute lymphoblastic leukemia in remission
  • adult acute myeloid leukemia in remission
  • childhood acute lymphoblastic leukemia in remission
  • recurrent adult acute lymphoblastic leukemia
  • recurrent adult acute myeloid leukemia
  • recurrent childhood acute lymphoblastic leukemia
  • recurrent childhood acute myeloid leukemia
  • secondary acute myeloid leukemia
  • myelodysplastic syndromes
  • childhood myelodysplastic syndromes
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Myelodysplastic Syndromes
  • Preleukemia



Fred Hutchinson Cancer Research Center Seattle, Washington  98109
Seattle Cancer Care Alliance Seattle, Washington  98109
OHSU Knight Cancer Institute Portland, Oregon  97239