Ignite Creation Date:
2024-05-06 @ 8:05 PM
Last Modification Date:
2024-10-26 @ 3:20 PM
Study NCT ID:
NCT06247917
Status:
RECRUITING
Last Update Posted:
2024-03-21
First Post:
2023-12-26
Brief Title:
Evaluate the Efficacy and Safety of Allogeneic Haematopoietic Stem Cell Transplantation With FBM Conditioning for MDS
Sponsor:
Ruijin Hospital
Organization:
Ruijin Hospital
Study Overview
Official Title:
A Prospective Single-arm Clinical Study to Evaluate the Efficacy and Safety of Allogeneic Haematopoietic Stem Cell Transplantation With FLU-BU-MEL Conditioning for Myelodysplastic Syndromes
Status:
RECRUITING
Status Verified Date:
2023-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To assess the safety and efficacy of FLU-BU-MEL as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with untreated MDS-EB or IPSS-R that is intermediate-risk 35 points high-risk or very high-risk The investigators conducted this clinical trialThere will be three phases to this trial screening therapy and follow-up A Screening phase Qualified patients are screened for trial participation by a medical history physical examination laboratory testing and disease evaluation after providing their informed consent B Treatment duration patients receive allogeneic hematopoietic stem cell transplantation prepped with Flu-Bu-Mel in accordance with the protocol C Follow-up period patients were checked on at the scheduled time to assess safety and efficacy HSCT conditioning regiment Flu 30 mgm2d d-6 days to d-2 9 intravenously over two hours MEL 50 mgm2d intravenously d-3 to d-2 BU 08 mgkgq6h d-6 to d-5 intravenously over 2 hours per drip Fludarabine and melphalan do not require a dose adjustment based on body weight however if body mass index BMI 25 ideal body weight IBW should be calculated as BMI25 and then determine Busulfan dosage based on corrected body weight AIBW25 AIBW25IBW25 x actual body weight - IBW
Detailed Description:
The only curative treatment for myelodysplastic syndromes MDS is allogeneic hematopoietic stem cell transplantation allo-HSCT which is also the most likely means of extending survival in patients who are at higher risk To maximize the survival advantage it is uncertain whether higher-risk patients should receive allo-HSCT directly or whether it should be done after demethylation treatment or chemotherapy to lower the primitive cell count According to retrospective investigations patients did not experience an OS benefit with pre-transplantation demethylation therapy Xixi Wang et al China G Damaj et al France12 In contrast to sequential allo-HSCT with chemotherapy and demethylation early allo-HSCT in patients with IPSS-scored high-riskvery high-risk MDS prolongs OS and improves survival according to another meta-analysis34 There is currently only one available randomized trial that evaluated the two treatment regimens 5 however it was prematurely stopped because of a delayed recruitment of patients 5 The Chinese recommendations for the Diagnosis and Treatment of Myelodysplastic Syndromes 2019 edition and other international recommendations suggest that patients can have demethylation or chemotherapy without postponing transplantation based on the evidence that is currently available On the other hand patients may be denied or delayed HSCT due to pre-transplant treatment toxicityThe traditional pretreatment strategy for myeloid tumors prior to transplantation was Busulfan with cyclophosphamide however in light of increased toxicity and treatment-related mortality fludarabine Flu-based pretreatment regimens have increasingly taken the place of the former Research indicates that patients treated with FluBu2FluBu3 had a significantly lower percentage of T cells reaching complete donor chimerism within 30 days than patients treated with BUCY Additionally patients who achieve complete remission CR prior to transplantation have an overall survival OS rate of 50-80 compared to 19-32 for those who do not achieve CR Finally the post-transplant recurrence rate can reach 506 7 indicating that FLU-BU is not recommended for individuals who are at high risk of recurrence and is not the best pretreatment regimen for immune reconstitution due to its limited antitumor impact Thus it is still a pressing problem to figure out how to boost the antitumor impact without making the pretreatment more hazardous
Yamamoto et al reported the effectiveness of sequential single-copy cord blood transplantation for unremitting AML based on FLU-BU FLU 30mgm2d6d BU 32mgkgd4d in combination with MEL 80mgm2 as a pretreatment regimen 8 in order to investigate the possibility of obtaining a more optimal regimen Out of 51 patients 46 underwent implantation and attained full donor chimerism The 2-year actual OS and progression-free survival PFS were 549 the 2-year cumulative RI was 196 the 100-day and 2-year cumulative NRM were 118 and 255 respectively indicating that there was no appreciable increase in toxicity and a greater antitumor efficacy with the MEL-enhanced FLU-BU regimen For the purpose of treating AMLMDS Tomoaki Ueda et al introduced MEL 100 mgm2 as a pretreatment regimen on top of FLUBU4 9 They demonstrated that all 42 patients were implanted and that full donor chimerism of T cells was attained in less than 30 days 4 years DFS 595 NRM 19 OS 66 While the 5-year RI of 538 was present in 31 of these non-CR individuals the group as a whole only had a 214 RI rateIn a multicenter prospective research involving AML and MDS Yoshimitsu Shimomura et al10 evaluated allogeneic hematopoietic stem cell transplantation for hematological neoplasms pretreated with FluBu4Mel and FluBu4 regimens Propensity score was the primary factor that matched the two patient groups The 5-year OS was higher in the FluBu4Mel group compared to the FluBu4 group 324 vs 301 log-rank P 0019 and there was no significant difference between the two groups in terms of non-recurrent deaths Additionally the 5-year recurrence rate and recurrence-associated mortality rate were significantly lower in the FluBu4 group than in the FluBu4 group
Based on prior research the FLU-BU-MEL regimen appears to be workable for treating AMLMDS It can also lower the rate of recurrence following allo-HSCT by providing a more potent anti-tumour effect and better implantation while the treatment-related death rate is generally within an acceptable range and may even increase patient survival In order to achieve this a single-arm open-ended single-centre phase II clinical study is suggested Its purpose is to assess the safety and effectiveness of the FLU-BU-MEL pretreatment regimen for the treatment of MDS in the untreated higher-risk group as well as to serve as a foundation for a prospective future randomized controlled trial
Yamamoto et al reported the effectiveness of sequential single-copy cord blood transplantation for unremitting AML based on FLU-BU FLU 30mgm2d6d BU 32mgkgd4d in combination with MEL 80mgm2 as a pretreatment regimen 8 in order to investigate the possibility of obtaining a more optimal regimen Out of 51 patients 46 underwent implantation and attained full donor chimerism The 2-year actual OS and progression-free survival PFS were 549 the 2-year cumulative RI was 196 the 100-day and 2-year cumulative NRM were 118 and 255 respectively indicating that there was no appreciable increase in toxicity and a greater antitumor efficacy with the MEL-enhanced FLU-BU regimen For the purpose of treating AMLMDS Tomoaki Ueda et al introduced MEL 100 mgm2 as a pretreatment regimen on top of FLUBU4 9 They demonstrated that all 42 patients were implanted and that full donor chimerism of T cells was attained in less than 30 days 4 years DFS 595 NRM 19 OS 66 While the 5-year RI of 538 was present in 31 of these non-CR individuals the group as a whole only had a 214 RI rateIn a multicenter prospective research involving AML and MDS Yoshimitsu Shimomura et al10 evaluated allogeneic hematopoietic stem cell transplantation for hematological neoplasms pretreated with FluBu4Mel and FluBu4 regimens Propensity score was the primary factor that matched the two patient groups The 5-year OS was higher in the FluBu4Mel group compared to the FluBu4 group 324 vs 301 log-rank P 0019 and there was no significant difference between the two groups in terms of non-recurrent deaths Additionally the 5-year recurrence rate and recurrence-associated mortality rate were significantly lower in the FluBu4 group than in the FluBu4 group
Based on prior research the FLU-BU-MEL regimen appears to be workable for treating AMLMDS It can also lower the rate of recurrence following allo-HSCT by providing a more potent anti-tumour effect and better implantation while the treatment-related death rate is generally within an acceptable range and may even increase patient survival In order to achieve this a single-arm open-ended single-centre phase II clinical study is suggested Its purpose is to assess the safety and effectiveness of the FLU-BU-MEL pretreatment regimen for the treatment of MDS in the untreated higher-risk group as well as to serve as a foundation for a prospective future randomized controlled trial
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None