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

Sponsor

Ciceri Fabio (Other)

Overall Status

Completed

CT.gov ID

NCT03961919

Collaborator

(none)

Enrollment

Location

Arm

154.6

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Myelodysplastic Syndromes Transplant-Related Hematologic Malignancy	Drug: Fludarabine Drug: ARA-C Drug: Treosulfan Procedure: Peripheral Blood Stem Cell Transplant	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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)

Actual Study Start Date :

Feb 10, 2009

Actual Primary Completion Date :

Dec 31, 2019

Actual Study Completion Date :

Dec 31, 2021

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: FLAT-Auto

Treosulfan in a combination regimen with ARA-C and fludarabine as conditioning therapy prior to autologous PBSCT

Drug: Fludarabine

Fludarabine i.v. 30 mg/m²/d day -6 to -2

Drug: ARA-C

Cytarabine i.v. 2 g/m²/d day -6 to -2

Drug: Treosulfan

Treosulfan i.v. 10 g/m²/d day -6 to -4

Procedure: Peripheral Blood Stem Cell Transplant

Autologous stem-cell transplantation i.v.: day 0 (source: peripheral blood) Pegylated-Filgrastim s.c. 6 mg day +3

Outcome Measures

Primary Outcome Measures

Evaluation of disease free survival from first Complete Remission (CR) [2 years after transplantation]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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