Treosulfan-based Conditioning for Transplantation in AML/MDS

Acute Myeloid Leukemia Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00491634
• Other study ID #: SHEBA-07-3116-AN-CTIL
• Status: Completed
• Phase: Phase 2
• First received: June 25, 2007
• Last updated: November 30, 2015
• Start date: June 2007
• Est. completion date: June 2014

Study information

• Verified date: November 2015
• Source: Sheba Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 68 Years

Eligibility

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 -

Study Design

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• treosulfan
12 g/m2 x 3 days
• Treosulfan
12 g/m2 x 3

Locations

Country	Name	City	State
Israel	Chaim Sheba Medical Center	Tel-Hashomer

Sponsors (1)

Lead Sponsor	Collaborator
Dr. Avichai Shimoni MD

Country where clinical trial is conducted

Israel, 

References & Publications (1)

Kröger 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	disease-free survival		2 years after transplantation	No
Secondary	treatment-related mortality, GVHD, relapse, overall survival		2 year after transplantation	Yes