Clinical trial NCT00491634: Treosulfan-based Conditioning for Transplantation in AML/MDS
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Myelodysplastic Syndrome
Keywords: acute myeloid leukemia
myelodysplastic syndrome
allogeneic stem cell transplantation
reduced-intensity conditioning
treosulfan
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
First posted: 2007-06-26
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Age less than physiologic 68 years.
2. 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).
3. 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
4. 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:

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

Primary outcomes:
measure: disease-free survival
timeFrame: 2 years after transplantation
Secondary outcomes:
measure: treatment-related mortality, GVHD, relapse, overall survival
timeFrame: 2 year after transplantation
Other outcomes:
Locations:
city: Tel-Hashomer
country: Israel
facility: Chaim Sheba Medical Center
Study officials:
affiliation: Chaim Sheba Medical Center
name: Arnon Nagler, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1038/sj.bmt.1705259.