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Treosulfan-based Conditioning for Transplantation in AML/MDS

Primary Purpose

Acute Myeloid Leukemia, Myelodysplastic Syndrome

Status

Completed

Phase

Phase 2

Locations

Israel

Study Type

Interventional

Intervention

treosulfan

Treosulfan

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring acute myeloid leukemia, myelodysplastic syndrome, allogeneic stem cell transplantation, reduced-intensity conditioning, treosulfan

Eligibility Criteria

18 Years - 68 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 -

Sites / Locations

Chaim Sheba Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

treosulfan

Outcomes

Primary Outcome Measures

disease-free survival

Secondary Outcome Measures

treatment-related mortality, GVHD, relapse, overall survival

Full Information

NCT ID

NCT00491634

First Posted

June 25, 2007

Last Updated

November 30, 2015

Sponsor

Dr. Avichai Shimoni MD

1. Study Identification

Unique Protocol Identification Number

NCT00491634

Brief Title

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

2. Study Status

Record Verification Date

November 2015

Overall Recruitment Status

Completed

Study Start Date

June 2007 (undefined)

Primary Completion Date

June 2014 (Actual)

Study Completion Date

June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Dr. Avichai Shimoni MD

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia, Myelodysplastic Syndrome

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

treosulfan

Intervention Type

Drug

Intervention Name(s)

treosulfan

Intervention Description

12 g/m2 x 3 days

Intervention Type

Drug

Intervention Name(s)

Treosulfan

Intervention Description

12 g/m2 x 3

Primary Outcome Measure Information:

Title

disease-free survival

Time Frame

2 years after transplantation

Secondary Outcome Measure Information:

Title

treatment-related mortality, GVHD, relapse, overall survival

Time Frame

2 year after transplantation

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

68 Years

Accepts Healthy Volunteers

Eligibility 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 -

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Arnon Nagler, MD

Organizational Affiliation

Chaim Sheba Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Chaim Sheba Medical Center

City

Tel-Hashomer

Country

Israel

12. IPD Sharing Statement

Citations:

PubMed Identifier

16415898

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.

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Treosulfan-based Conditioning for Transplantation in AML/MDS

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