Treosulfan and Fludarabine in Treating Younger Patients Who Are Undergoing a Donor Stem Cell Transplant for Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome - Full Text View

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00253513

Purpose

RATIONALE: Drugs used in chemotherapy, such as treosulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving treosulfan and fludarabine together with a donor bone marrow transplant or a peripheral stem cell transplant may be an effective treatment for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome.

PURPOSE: This phase II trial is studying giving treosulfan together with fludarabine to see how well it works in treating patients who are undergoing a donor stem cell transplant for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes	Drug: fludarabine phosphate Drug: treosulfan Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation Procedure: radiation therapy	Phase II

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Fludarabine Fludarabine monophosphate Treosulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Study of a Reduced-Intensity Conditioning Regimen With Treosulfan and Fludarabine for Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Leukemia

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Incidence of severe to fatal regimen-related toxicity to major organ systems (cardiac, bladder/renal, pulmonary, hepatic, neurologic and gastrointestinal) between days -6 and 28 [ Designated as safety issue: Yes ]
Incidence of graft failure [ Designated as safety issue: No ]
Incidence of nonrelapse mortality by day 200 (second phase only) [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	June 2005
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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

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.

Eligibility

Ages Eligible for Study:	up to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of acute myeloid leukemia, lymphoblastic leukemia, or myelodysplastic syndrome
- 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 typing
  - A single allele mismatch allowed

PATIENT CHARACTERISTICS:

Performance status

Karnofsky 70-100% OR
Lansky 70-100%

Life expectancy

Not specified

Hematopoietic

Not specified

Hepatic

Bilirubin ≤ 2 times upper limit of normal (ULN)
AST ≤ 2 times ULN
No evidence of synthetic dysfunction
No severe cirrhosis
No active infectious hepatitis

Renal

Creatinine clearance ≥ 50%
Creatinine ≤ 2 times ULN
Dialysis independent

Cardiovascular

No cardiac insufficiency requiring treatment
No symptomatic coronary artery disease
Ejection fraction ≥ 35% (for patients with history of cardiac disease or anthracycline exposure)

Pulmonary

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

Other

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

See Disease Characteristics
No prior allogeneic bone marrow or stem cell transplantation
No concurrent umbilical cord blood or autologous transplantation

Chemotherapy

See Disease Characteristics

Radiotherapy

See Disease Characteristics

Other

More than 4 weeks since prior experimental drugs
Concurrent enrollment on another protocol for graft-versus-host disease prophylaxis allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00253513

Locations

United States, Oregon
Oregon Health and Science University Cancer Institute
Portland, Oregon, United States, 97239-3098
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

H. Joachim Deeg, MD

Fred Hutchinson Cancer Research Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	Fred Hutchinson Cancer Research Center ( H. Joachim Deeg )
Study ID Numbers:	CDR0000445306, FHCRC-1931.00, MEDAC-FHCRC-1931.00, OHSU-HEM-05107-LM
Study First Received:	November 11, 2005
Last Updated:	November 8, 2008
ClinicalTrials.gov Identifier:	NCT00253513
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Leukemia, Lymphoid
Precancerous Conditions
Leukemia, Myeloid, Acute
Acute lymphoblastic leukemia, adult
Leukemia
Preleukemia
Neoplasm Metastasis
Acute myeloid leukemia, adult
Lymphoma
Acute myelocytic leukemia
Myelodysplastic syndromes
Immunoproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma

Hematologic Diseases
Myelodysplastic Syndromes
Myelodysplasia
Acute myelogenous leukemia
Leukemia, Myeloid
Fludarabine monophosphate
Recurrence
Lymphatic Diseases
Fludarabine
Lymphoproliferative Disorders
Bone Marrow Diseases
Treosulfan

Additional relevant MeSH terms:

Antimetabolites
Neoplasms by Histologic Type
Disease
Antimetabolites, Antineoplastic
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs

Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Pathologic Processes
Therapeutic Uses
Syndrome
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on January 14, 2009