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Treosulfan-based Conditioning for Transplantation in AML/MDS

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Dr. Avichai Shimoni MD, Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT00491634
First received: June 25, 2007
Last updated: December 1, 2012
Last verified: December 2012
History of Changes
  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 2

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

Resource links provided by NLM:

U.S. FDA Resources

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 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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:

  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 -
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00491634

Locations
Israel
Chaim Sheba Medical Center
Tel-Hashomer, Israel
Sponsors and Collaborators
Dr. Avichai Shimoni MD
Investigators
Principal Investigator: Arnon Nagler, MD Chaim Sheba Medical Center
  More Information

Publications:

Responsible Party: Dr. Avichai Shimoni MD, Dr. Avichai Shimoni, Sheba Medical Center
ClinicalTrials.gov Identifier: NCT00491634     History of Changes
Other Study ID Numbers: SHEBA-07-3116-AN-CTIL
Study First Received: June 25, 2007
Last Updated: December 1, 2012
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

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Treosulfan
 Busulfan
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Myeloablative Agonists

ClinicalTrials.gov processed this record on May 16, 2013