NCT00822393CompletedPhase 3
Clinical Phase III Trial to Compare Treosulfan-based Conditioning Therapy With Busulfan-based Reduced-intensity Conditioning (RIC) Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients With AML or MDS Considered Ineligible to Standard Conditioning Regimens
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- medac GmbH
- Enrollment
- 570
- Locations
- 33
- Primary Endpoint
- Event-free survival (EFS)
Study Overview
Brief Summary
This randomized allogeneic transplantation protocol compares i.v. Treosulfan-based conditioning therapy with reduced intensity i.v. Busulfan-based conditioning in adult AML and MDS patients at increased risk for standard conditioning therapies. The protocol is based on results of previous phase I/II trials evaluating Treosulfan/Fludarabine conditioning prior to allogeneic haematopoietic stem cell transplantation. The reference arm (reduced intensity i.v. Busulfan/Fludarabine) is considered to be accepted medical practice for the study patient population.
Detailed Description
To compare efficacy and safety of Treosulfan-based conditioning (test) with i.v. Busulfan-based reduced intensity conditioning (reference).
The statistical aim of the study is to show non-inferiority with respect to:
Event-free survival (EFS) within 2 years after transplantation. Events are defined as relapse of disease, graft failure or death (whatever occurs first).
- Comparative evaluation of incidence of CTC grade III/IV mucositis/stomatitis between day -6 and day +28
- Comparative evaluation of overall survival (OS) and cumulative incidence of relapse (RI) as well as non-relapse mortality (NRM) and transplantation-related mortality (TRM)within 2 years after transplantation
- Comparative evaluation of day +28 conditional cumulative incidence of engraftment
- Comparative evaluation of day +28 and day +100 incidence of complete donor-type chimerism
- Comparative evaluation of cumulative incidence of acute and chronic GvHD within 2 years after transplantation
- Comparative evaluation of incidence of other CTC grade III/IV adverse events between day -6 and day +28
Individual patients will be followed-up for at most 2 years after transplantation. Three confirmatory interim evaluations and one final analysis are planned, which allow to stop the trial as soon as the question of non-inferiority is answered (as outlined below). In addition, post-surveillance with respect to OS and EFS will be conducted one year after transplantation of the last randomised patient.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients with acute myeloid leukaemia acc. to WHO, 2008 (AML in complete remission at transplant, i.e. blast counts < 5 % in bone marrow) or myelodysplastic syndrome acc. to WHO, 2008 (MDS with blast counts < 20 % in bone marrow during disease history) indicated for allogeneic haematopoietic progenitor cell transplantation 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 a HCT-CI score > 2 [acc. to Sorror et al., 2005]
- •Availability of an HLA-identical sibling donor (MRD) or HLA-identical unrelated donor (MUD). 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. In case, no class I and class II completely identical donor (10 out of 10 gene loci) can be identified, one antigen disparity (class I) and/or one allele disparity (class II) between patient and donor are acceptable. Conversely, disparity of two antigens (irrespective of the involved gene loci) cannot be accepted. These definitions for the required degree of histocompatibility apply to the selection of related as well as of unrelated donors.
- •Adult patients of both gender, age 18 - 70 years
- •Karnofsky Index ≥ 60 %
- •Written informed consent
- •Men capable of reproduction and women of childbearing potential must be willing to consent to using a highly effective method of birth control such as condoms, implants, injectables, combined oral contraceptives, IUDs, sexual abstinence or vasectomised partner while on treatment and for at least 6 months thereafter
Exclusion Criteria
- •Patients with acute promyelocytic leukaemia with t(15;17)(q22;q12) and in CR1
- •Patients considered contra-indicated for allogeneic HSCT due to severe concomitant illness (within three weeks prior to 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 hyperbilirubinaemia > 3 x ULN or ALT / AST > 5 x ULN
- •Active malignant involvement of the CNS
- •HIV-positivity, active non-controlled infectious disease under treatment (no decrease of CRP or PCT) including active viral liver infection
- •Previous allogeneic HSCT
- •Pleural effusion or ascites > 1.0 L
- •Pregnancy or lactation
- •Known hypersensitivity to treosulfan, busulfan and/or related ingredients
- •Participation in another experimental drug trial within 4 weeks prior to day -6 of the protocol
- •Non-cooperative behaviour or non-compliance
- •Psychiatric diseases or conditions that might compromise the ability to give informed consent
Arms & Interventions
1
Active Comparator
Busulfan
Intervention: Busulfan (Drug)
2
Experimental
Treosulfan
Intervention: Treosulfan (Drug)
Outcomes
Primary Outcomes
Event-free survival (EFS)
Time Frame: within 2 years after transplantation
Secondary Outcomes
- Comparative evaluation of incidence of CTC grade III/IV mucositis/stomatitis between day -6 and day +28(between day -6 and day +28)
Investigators
Study Sites (33)
Loading locations...
Similar Trials
Unknown
Phase 2
MiniMUD Study - Unrelated Reduced Intensity Conditioning With Treosulfan® for Allogeneic Stem Cell Transplantation in Patients With Hematological MalignanciesHematological MalignanciesAllogeneic TransplantationNCT00129155Hospices Civils de Lyon30
Completed
Phase 2
Treosulfan-based Versus Busulfan-based Conditioning in Paediatric Patients With Non-malignant DiseasesPrimary ImmunodeficienciesHaemoglobinopathiesBone Marrow Failure SyndromesInborn Errors of MetabolismNCT02349906medac GmbH106
Completed
Phase 2
Allogeneic Stem Cell Transplantation (SCT) With Treosulfan, VP-16 and Cyclophosphamid for Patients With Acute Lymphoblastic Leukemia (ALL)Acute Lymphoblastic LeukemiaNCT00682305Universitätsklinikum Hamburg-Eppendorf50
Active, not recruiting
Phase 1
Conditioning treatment with treosulfan or busulfan for chemotherapy prior to stem cell transplantation in patients with leukemia.EUCTR2008-002356-18-DEmedac Gesellschaft für klinische Spezialpräparate mbH960
Active, not recruiting
Phase 1
Clinical phase III trial to compare Treosulfan-based conditioning therapy with Busulfan-based reduced-intensity conditioning (RIC) prior to allogeneic haematopoietic stem cell transplantation in patients with AML or MDS considered ineligible to standard conditioning regimens - Clinical Phase III Treosulfan based conditioning vs RICPatients with acute myeloid leukaemia (AML)or myelodysplastic syndrome (MDS) considered ineligible to standard conditioning therapies prior to allogenic stem cell transplantationMedDRA version: 9.1Level: LLTClassification code 10000881Term: Acute myeloid leukaemia (in remission)MedDRA version: 9.1Level: LLTClassification code 10028534Term: Myelodysplastic syndrome NOSEUCTR2008-002356-18-ITMEDAC RESEARCH545
Related News
FDA Approves Treosulfan Plus Fludarabine for Allo-HSCT Conditioning in AML and MDS- The FDA approved treosulfan with fludarabine as a conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in AML and MDS patients.
- The approval was based on the MC-FludT.14/L Trial II, which demonstrated improved overall survival compared to busulfan-based conditioning.
- Treosulfan offers a new option for adult and pediatric patients, potentially enhancing survival while minimizing side effects in allo-HSCT.
- Common adverse events included musculoskeletal pain, stomatitis, pyrexia, nausea, edema, and infection, aligning with typical post-transplant observations.last yearFDA Approves GRAFAPEX (Treosulfan) for Injection in AlloHSCT Conditioning Regimen- The FDA has approved GRAFAPEX (treosulfan) in combination with fludarabine for allogeneic hematopoietic stem cell transplantation (alloHSCT) conditioning.
- GRAFAPEX is indicated for adult and pediatric patients (1 year+) with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
- Clinical trials showed GRAFAPEX, combined with fludarabine, improved overall survival compared to busulfan-based regimens in transplant settings.
- Medexus Pharmaceuticals plans to launch GRAFAPEX in the first half of 2025, projecting potential annual revenue exceeding $100 million within five years.last yearKey Oncology Updates: Approvals, Designations, and Trial Results- Treosulfan gains FDA approval for allogeneic hematopoietic stem cell transplantation conditioning in AML and MDS, offering a new option for adult and pediatric patients.
- The FDA grants priority review to RP1 plus nivolumab for advanced melanoma after PD-1 inhibitor failure, with a decision expected by July 2025.
- Dato-DXd receives breakthrough therapy designation from the FDA for pretreated EGFR-mutated NSCLC, based on promising phase 2 and 3 trial data.last year