Treosulfan, fludarabine and cyclophosphamide as a preparative chemotherapy regimen before haploidentical blood or marrow stem cell transplantatio

Phase 1

• Conditions: Conditioning therapy before haploidentical hematopoietic stem cell transplantation; MedDRA version: 22.0Level: LLTClassification code 10059044Term: Allogeneic peripheral hematopoietic stem cell transplantSystem Organ Class: 100000004865; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2021-004730-11-AT
• Lead Sponsor: Medical University of Vienna

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-01-04
• Last Update Posted: 2 March 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1.Patients with acute myeloid leukemia (AML) according to WHO 2016 (AML in complete remission at transplant, i.e., blast counts <5% in bone marrow) or myelodysplastic syndrome according to WHO 2016 (MDS with blast counts <20 % in bone marrow during disease history) indicated for haploidentical HSCT but considered to be at increased risk for standard conditioning therapies according to the following criteria:
•patients aged =50 years at transplant and/or
•patients with an HCT-CI score >2 [according to Sorror et al., 2005]
2.Availability of a haploidentical (HLA match =5/10) first- or second-degree related donor. Donor selection is based on molecular high-resolution typing (4 digits) of class II alleles of the DRB1 and DQB1 gene loci and molecular (at least) low-resolution typing (2 digits) of class I alleles (i.e., antigens) of the HLA- A, B, and C gene loci.
3.Adult patients of both gender, age 18-70 years
4.Karnofsky Index =60 %
5.Written informed consent
6.Men capable of reproduction and women of childbearing potential must be willing to consent to use a highly effective method of birth control such as condoms, implants, injectables, combined oral contraceptives, IUDs, sexual abstinence, or vasectomized partner while on treatment and for at least 6 months thereafter

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1.Availability of matched sibling donor eligible for stem cell donation
2.Patients with acute promyelocytic leukemia with t(15;17)(q22;q12) and in CR1
3.Patients considered contraindicated for HSCT due to severe concomitant illness (within 3 weeks before scheduled day -6):
•patients with severe renal impairment like patients on dialysis or prior renal transplantation or S-creatinine >3.0 x ULN or calculated creatinine-clearance < 60 ml/min
•patients with severe pulmonary impairment, DLCOsb (Hb-adjusted)/or FEV1 <50 % or severe dyspnoea at rest or requiring oxygen supply
•patients with severe cardiac impairment diagnosed by echocardiography and LVEF <40 %
•patients with severe hepatic impairment indicated by hyperbilirubinemia >3x ULN or ALT/AST >5 x ULN
4.Active malignant involvement of the CNS
5.HIV-positivity, active non-controlled infectious disease under treatment (no decrease of CRP or PCT) including active viral liver infection
6.Previous allogeneic HSCT
7.Pleural effusion or ascites > 1.0L
8.Pregnancy or lactation
9.Known hypersensitivity to treosulfan, fludarabine, cyclophosphamide and/or related ingredients
10.Participation in another experimental drug trial within 4 weeks before day -6 of the protocol
11.Non-cooperative behavior or non-compliance
12.Psychiatric diseases or conditions that might compromise the ability to give informed consent

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: •To assess the efficacy and safety of TreoFC conditioning before haploidentical hematopoietic stem cell transplantation (HSCT) in older or comorbid patients. The primary endpoint is overall survival (OS) 1 year after haploidentical HSCT.;Secondary Objective: •To assess rates of non-relapse mortality (NRM), relapse-free survival (RFS), graft-versus-host disease (GVHD) and relapse-free survival (GRFS), acute GVHD, chronic GVHD, quality of life (QOL), toxicity, engraftment, and chimerism in the study population.;Primary end point(s): Overall survival ;Timepoint(s) of evaluation of this end point: 1 year after haploidentical HSCT

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Cumulative incidence of relapse <br>•Relapse-free survival (RFS)<br>•Graft-versus-host disease and relapse-free survival (GRFS)<br>•Cumulative incidence of non-relapse mortality (NRM) a<br>•Cumulative incidence of acute graft-versus-host disease (GVHD) a<br>•Cumulative incidence of chronic GVHD<br>•Toxicities according to the current version of the NCI CTCAE<br>•Engraftment<br>•Chimerism<br><br>;Timepoint(s) of evaluation of this end point: 1 year after haploidentical HSCT