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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)


Phase 2
N/A
60 Years
Open (Enrolling)
Both
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

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Trial Information

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)


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.


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
evaluation

- 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
leukapheresis

- 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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Relapse incidence to < 15%

Outcome Time Frame:

At 6 months

Safety Issue:

No

Principal Investigator

Boglarka Gyurkocza

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Food and Drug Administration

Study ID:

2272.00

NCT ID:

NCT00860574

Start Date:

February 2009

Completion Date:

Related Keywords:

  • 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
  • Congenital Abnormalities
  • Blast Crisis
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Accelerated Phase
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myelomonocytic, Chronic
  • Myelodysplastic Syndromes
  • Preleukemia
  • Leukemia, Myelomonocytic, Acute

Name

Location

Fred Hutchinson Cancer Research Center/University of Washington Cancer ConsortiumSeattle, Washington  98109
University of ColoradoDenver, Colorado  80217
Oregon Health and Science UniversityPortland, Oregon  97201