Phase II Trial in Elderly Patients With AML or MDS in Complete Remission Not Eligible for Allogenic Transplant

Study Overview
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Brief Summary
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FLAT-Auto is a phase II trial. fludarabine and ARA-C will be combined with the alkylating agent treosulfan (FLAT), to investigate the feasibility and the efficacy of a new regimen, supported with autologous peripheral blood SCT (PBSCT), as final postremission consolidation in AML/MDS elderly patients.

Official Title
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Evaluation of Safety and Efficacy of Treosulfan-cytarabine-fludarabine (FLAT) Combination Prior to Autologous Stem Cell Transplant (HSCT) in Elderly Patients With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

Conditions
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Acute Myeloid Leukemia, Myelodysplastic Syndromes, Transplant-Related Hematologic Malignancy

Intervention / Treatment
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* Drug: Fludarabine
* Drug: ARA-C
* Drug: Treosulfan
* Procedure: Peripheral Blood Stem Cell Transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pts with de novo or secondary AML or with Int 2 or High risk MDS according to IPSS. Pts unable or unfit to receive SCT from an HLA (human leukocyte antigen)-identical related (SIB) or unrelated (MUD), or HLA-haploidentical related (HAPLO) donor. Hematologic CR (Appendix D) after 1 or 2 cycles of induction standard chemotherapy. Successful collection of autologous PBSC: ≥ 5.0x10e6 /kg patient bodyweight (BW) Age ≥ 65 years. Performance status 0-2 ECOG (Eastern Cooperative Oncology Group), 60-100% Karnofsky (Appendix E). Written informed consent. Exclusion Criteria: Diagnosis of AML M3. Second concomitant malignancies. Severe concomitant illnesses/medical conditions (e.g. impaired respiratory and/or cardiac function). Known and manifested malignant involvement of the central nervous system (CNS) Active infectious disease HIV- positivity or active hepatitis infection Impaired liver function (bilirubin > 1.5 x upper normal limit; transaminases > 3.0 x upper normal limit) Impaired renal function (creatinine-clearance < 60 ml/min; serum creatinine > 1.5 x upper normal limit). Known hypersensitivity to treosulfan and/or cytarabine and/or fludarabine Participation in another experimental drug trial within 4 weeks before day -6 Non-cooperative behaviour or non-compliance Psychiatric diseases or conditions that might impair the ability to give informed consent

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FLAT-Auto<br>Treosulfan in a combination regimen with ARA-C and fludarabine as conditioning therapy prior to autologous PBSCT | Drug: Fludarabine<br>* Fludarabine i.v. 30 mg/m²/d day -6 to -2<br>Drug: ARA-C<br>* Cytarabine i.v. 2 g/m²/d day -6 to -2<br>Drug: Treosulfan<br>* Treosulfan i.v. 10 g/m²/d day -6 to -4<br>Procedure: Peripheral Blood Stem Cell Transplant<br>* Autologous stem-cell transplantation i.v.: day 0 (source: peripheral blood) Pegylated-Filgrastim s.c. 6 mg day +3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of disease free survival from first Complete Remission (CR) | Evaluation of disease-free survival (DFS) duration from documented first CR of AML or MDS with intermediate 2 or high IPSS (International Prognostic Score System). | 2 years after transplantation |