Ruxolitinib and Chidamide Intensified Bu/CY Conditioning Regimen

Peripheral Blood Stem Cell Transplantation Clinical Trial

Official title:

Ruxolitinib and Chidamide Intensified Bu/CY Conditioning Regimen for Patients With Acute B Cell Lymphoblast Leukemia Underwenting Haploidenticl Peripheral Blood Stem Cell Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05088226
• Other study ID #: S2020-483-01
• Status: Recruiting
• Phase: Phase 2
• Start date: December 1, 2021
• Est. completion date: June 1, 2023

Study information

• Verified date: October 2021
• Source: Chinese PLA General Hospital
• Contact: Daihong Liu
• Phone: 86-13681171597
• Email: daihongrm[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the efficacy and safety of Ruxolitinib and Chidamide intensified conditioning regimen in patients with Acute B cell Lymphoblast leukemia Underwenting Haploidenticl Peripheral blood Stem Cell Transplantation.

Description:

Haploidenticl Peripheral blood Stem Cell Transplantation should be offered to eligible patients with Acute B cell Lymphoblast leukemia whenever feasible. To further improve the outcome of transplantation patients with Acute B cell Lymphoblast leukemia, we developed a modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Chidamide. In this study, we tested the efficacy and feasibility of the modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Chidamide in patients with Acute B cell Lymphoblast leukemia undergoing allogeneic peripheral blood stem cell transplantation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: June 1, 2023
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 65 Years

Eligibility

Inclusion Criteria:

1. high risk acute B cell lymphoblastic leukemia with the indications for allogeneic transplantation;

2. Have matched sibling donors, =8/10 HLA matched unrelated donors or haploidentical donors

3. All patients should aged 12 to 65 years;

4. Liver function: ALT and AST=2.5 times the upper limit of normal , bilirubin=2 times the upper limit of normal;

5. Renal function: creatinine =the upper limit of normal;

6. Patients without any uncontrolled infections , without organ dysfunction or without severe mental illness;

7. Eastern Cooperative Oncology Group (ECOG) performance status =2;

8. Have signed informed consent.

Exclusion Criteria:

1. pregnant women;

2. Patients with mental illness or other states unable to comply with the protocol;

3. ALL patients with Ph positive;

Related Conditions & MeSH terms

• Peripheral Blood Stem Cell Transplantation

Intervention

Drug:
• Ruxolitinib combined with Chidamide.
Drug: modified By/Cy conditioning regimen intensified by Ruxolitinib and Chidamide . Day -15 # Ruxolitinib 70mg bid, Chidamide 30 mg once; Day -14 # Ruxolitinib 70mg bid; Day -13 # Ruxolitinib 70mg bid; Day -12 # Ruxolitinib 70mg bid, Chidamide 30 mg once; Day -11 # Ruxolitinib 70mg bid; Day-10# Cytarabine 4g/m2/day CI , Ruxolitinib 60mg bid; Day- 9# Cytarabine 4g/m2/day CI, Ruxolitinib 60mg bid; Day- 8 # Busulfan 0.8mg/ kg Q6h iv, Ruxolitinib 50mg bid, Chidamide 30 mg once; Day- 7# Busulfan 0.8mg/ kg Q6h iv, Ruxolitinib 50mg bid; Day-6# Busulfan 0.8mg/kg Q6h iv, Ruxolitinib 40mg bid; Day-5# Cyclophosphamide 1.8 g/m2/day CI, Ruxolitinib 30mg bid, Chidamide 30 mg once; Day-4# Cyclophosphamide 1.8 g/m2/day CI,Ruxolitinib 20mg bid; Day-3# Carmustine 250mg/m2/ day iv, Ruxolitinib 10mg bid; Day-2# Ruxolitinib 5mg bid, Chidamide 30 mg/day; Day-1# Ruxolitinib 5mg qd;

Locations

Country	Name	City	State
China	Chinese PLA General Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Chinese PLA General Hospital

Country where clinical trial is conducted

China, 

References & Publications (6)

Delgado-Martin C, Meyer LK, Huang BJ, Shimano KA, Zinter MS, Nguyen JV, Smith GA, Taunton J, Winter SS, Roderick JR, Kelliher MA, Horton TM, Wood BL, Teachey DT, Hermiston ML. JAK/STAT pathway inhibition overcomes IL7-induced glucocorticoid resistance in a subset of human T-cell acute lymphoblastic leukemias. Leukemia. 2017 Dec;31(12):2568-2576. doi: 10.1038/leu.2017.136. Epub 2017 May 9. — View Citation

Ding YY, Stern JW, Jubelirer TF, Wertheim GB, Lin F, Chang F, Gu Z, Mullighan CG, Li Y, Harvey RC, Chen IM, Willman CL, Hunger SP, Li MM, Tasian SK. Clinical efficacy of ruxolitinib and chemotherapy in a child with Philadelphia chromosome-like acute lymphoblastic leukemia with GOLGA5-JAK2 fusion and induction failure. Haematologica. 2018 Sep;103(9):e427-e431. doi: 10.3324/haematol.2018.192088. Epub 2018 May 17. — View Citation

Ferrante F, Giaimo BD, Bartkuhn M, Zimmermann T, Close V, Mertens D, Nist A, Stiewe T, Meier-Soelch J, Kracht M, Just S, Klöble P, Oswald F, Borggrefe T. HDAC3 functions as a positive regulator in Notch signal transduction. Nucleic Acids Res. 2020 Apr 17;48(7):3496-3512. doi: 10.1093/nar/gkaa088. — View Citation

Maude SL, Dolai S, Delgado-Martin C, Vincent T, Robbins A, Selvanathan A, Ryan T, Hall J, Wood AC, Tasian SK, Hunger SP, Loh ML, Mullighan CG, Wood BL, Hermiston ML, Grupp SA, Lock RB, Teachey DT. Efficacy of JAK/STAT pathway inhibition in murine xenograft models of early T-cell precursor (ETP) acute lymphoblastic leukemia. Blood. 2015 Mar 12;125(11):1759-67. doi: 10.1182/blood-2014-06-580480. Epub 2015 Feb 2. — View Citation

Savino AM, Sarno J, Trentin L, Vieri M, Fazio G, Bardini M, Bugarin C, Fossati G, Davis KL, Gaipa G, Izraeli S, Meyer LH, Nolan GP, Biondi A, Te Kronnie G, Palmi C, Cazzaniga G. The histone deacetylase inhibitor givinostat (ITF2357) exhibits potent anti-tumor activity against CRLF2-rearranged BCP-ALL. Leukemia. 2017 Nov;31(11):2365-2375. doi: 10.1038/leu.2017.93. Epub 2017 Mar 23. — View Citation

Shi Y, Jia B, Xu W, Li W, Liu T, Liu P, Zhao W, Zhang H, Sun X, Yang H, Zhang X, Jin J, Jin Z, Li Z, Qiu L, Dong M, Huang X, Luo Y, Wang X, Wang X, Wu J, Xu J, Yi P, Zhou J, He H, Liu L, Shen J, Tang X, Wang J, Yang J, Zeng Q, Zhang Z, Cai Z, Chen X, Ding K, Hou M, Huang H, Li X, Liang R, Liu Q, Song Y, Su H, Gao Y, Liu L, Luo J, Su L, Sun Z, Tan H, Wang H, Wang J, Wang S, Zhang H, Zhang X, Zhou D, Bai O, Wu G, Zhang L, Zhang Y. Chidamide in relapsed or refractory peripheral T cell lymphoma: a multicenter real-world study in China. J Hematol Oncol. 2017 Mar 15;10(1):69. doi: 10.1186/s13045-017-0439-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants relapse as assessed by NCCN (National Comprehensive Cancer Network ) criteria	Defined as the proportion of participants whose underlying malignancy relapsed.	365 days after transplantation
Secondary	DFS(disease-free survival )	DFS was defined as survival with no evidence of relapse or progression.	365 days after transplantation
Secondary	TRM(treatment-related mortality )	Defined as the proportion of subjects who died due to causes other than malignancy relapse.	365 days after transplantation
Secondary	Proportion of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria)	Defined as the proportion of participants who developed acute GVHD.	365 days after transplantation
Secondary	Proportion of participants with cGVHD as assessed by chronic graft versus host disease grading criteria (refer to NIH criteria)	Defined as the proportion of participants who developed chronic GVHD.	365 days after transplantation
Secondary	OS(overall survival )	OS was defined as the time from transplantation to death due to any cause.	365 days after transplantation
Secondary	Failure-free survival (FFS)	Defined as the time from tranplantation to the earliest date that a participant died, had a relapse/progression of the underlying malignancy, required additional therapy for aGVHD, or demonstrated signs or symptoms of chronic graft-versus-host disease (cGVHD).	365 days after transplantation
Secondary	infection rate	Defined as the proportion of participants who developed all kinds of infection.	365 days after transplantation