Treosulfan-Based Conditioning for Transplantation in AML/MDS - Full Text View

Sponsored by:	Sheba Medical Center
Information provided by:	Sheba Medical Center
ClinicalTrials.gov Identifier:	NCT00491634

Purpose

The study hypotheses is that the introduction of dose escalated treosulfan, in substitution to busulfan, will reduce toxicity after allogeneic transplantation while improving myeloablation and and disease control in patients with AML and MDS not eligible for standard transplantation.

Condition	Intervention	Phase
Acute Myeloid Leukemia Myelodysplastic Syndrome	Drug: treosulfan Drug: Treosulfan	Phase II

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Fludarabine Fludarabine monophosphate Treosulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Historical Control, Single Group Assignment, Safety/Efficacy Study
Official Title:	Phase II Trial of Fludarabine Combined With Intravenous Treosulfan and Allogeneic Hematopoietic Stem-Cell Transplantation in Patients With Chemo-Refractory or Previously Untreated Acute Myeloid Leukemia and Myelodysplastic Syndrome.

Further study details as provided by Sheba Medical Center:

Primary Outcome Measures:

disease-free survival [ Time Frame: 2 years after transplantation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

treatment-related mortality, GVHD, relapse, overall survival [ Time Frame: 2 year after transplantation ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	24
Study Start Date:	June 2007
Estimated Study Completion Date:	June 2009
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental treosulfan	Drug: treosulfan 12 g/m2 x 3 days Drug: Treosulfan 12 g/m2 x 3

Eligibility

Ages Eligible for Study:	18 Years to 68 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age less than physiologic 68 years.
Patients with AML and MDS not eligible for standard TBI- or Busulfan-based myeloablative conditioning due to age, concurrent medical condition, or extensive prior therapy (e.g. age > 55 years for HLA-matched sibling transplants or > 50 for matched unrelated donor transplants, prior / concomitant pulmonary, liver, or other organ complications).
This study will only include patients with chemo-refractory disease or previously untreated active disease.

A. acute myeloid leukemias (AML) according to WHO classification (> 20% myeloblasts in peripheral blood or bone marrow at diagnosis) in induction failure, PR, untreated or chemo-refractory relapse. Patients must have > 10% marrow blasts at the time of transplantation.

B. myelodysplastic syndromes (MDS) according to WHO classification (< 20% myeloblasts in peripheral blood and bone marrow at diagnosis), indicated for allogeneic transplantation:

- refractory anaemia with excess blasts (RAEB-1 and RAEB-2) with no prior therapy
Patients must have an HLA matched related or unrelated donor willing to donate either peripheral blood stem cells or bone marrow. Matching is based on high-resolution class I (HLA-A, -B, -C) and class II (HLA-DRB1, -DQB1) typing. The goal is to transplant > 3 x 106 CD34+ cells per kg body weight of the recipient -

Exclusion Criteria:

Bilirubin > 3.0 mg/dl, transaminases > 3 times upper normal limit
Creatinine > 2.0 mg/dl
ECOG-Performance status > 2
Uncontrolled infection
Pregnancy or lactation
Abnormal lung diffusion capacity (DLCO < 40% predicted)
Severe cardiovascular disease
CNS disease involvement
Pleural effusion or ascites > 1 liter
Known hypersensitivity to fludarabine or treosulfan
Psychiatric conditions/disease that impair the ability to give informed consent or to adequately co-operate -

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00491634

Contacts

Contact: Avichai Shimoni, MD

972 3 530 5830

ashimoni@sheba.health.gov.il

Locations

Israel
Chaim Sheba Medical Center	Recruiting
Tel-Hashomer, Israel
Principal Investigator: Arnon Nagler, MD

Sponsors and Collaborators

Sheba Medical Center

Investigators

Principal Investigator:

Arnon Nagler, MD

Chaim Sheba Medical Center

More Information

Publications:

Kroger N, Shimoni A, Zabelina T, Schieder H, Panse J, Ayuk F, Wolschke C, Renges H, Dahlke J, Atanackovic D, Nagler A, Zander A. Reduced-toxicity conditioning with treosulfan, fludarabine and ATG as preparative regimen for allogeneic stem cell transplantation (alloSCT) in elderly patients with secondary acute myeloid leukemia (sAML) or myelodysplastic syndrome (MDS). Bone Marrow Transplant. 2006 Feb;37(4):339-44.

Responsible Party:	Chaim Sheba Medical Center ( Arnon Nagler MD )
Study ID Numbers:	SHEBA-07-3116-AN-CTIL
Study First Received:	June 25, 2007
Last Updated:	January 22, 2008
ClinicalTrials.gov Identifier:	NCT00491634
Health Authority:	Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Sheba Medical Center:

acute myeloid leukemia
myelodysplastic syndrome
allogeneic stem cell transplantation
reduced-intensity conditioning
treosulfan

Study placed in the following topic categories:

Myelodysplastic syndromes
Precancerous Conditions
Hematologic Diseases
Myelodysplastic Syndromes
Myelodysplasia
Acute myelogenous leukemia
Leukemia, Myeloid
Fludarabine monophosphate

Leukemia, Myeloid, Acute
Leukemia
Preleukemia
Fludarabine
Treosulfan
Bone Marrow Diseases
Acute myelocytic leukemia

Additional relevant MeSH terms:

Neoplasms
Pathologic Processes
Disease
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

Therapeutic Uses
Syndrome
Antineoplastic Agents, Alkylating
Alkylating Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009