Ruxolitinib and Chidamide for Acute T Cell Lymphoblast Leukemia/ Lymphoblastic Lymphoma

NCT05075681 | Unknown Phase 1

• 1 other identifier: S-2020-483-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Peripheral Blood Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• DFS(disease-free survival )

  365 days after transplantation

• TRM(treatment-related mortality )

  365 days after transplantation

• Proportion of participants with aGVHD as assessed by acute graft versus host disease grading criteria (refer to Glucksberg criteria)

  100 days after transplantation

• Proportion of participants with cGVHD as assessed by chronic graft versus host disease grading criteria (refer to NIH criteria)

  365 days after transplantation

• OS(overall survival )

  365 days after transplantation

Study Arms (1)

Ruxolitinib combined with Chidamide

EXPERIMENTAL

All recipients in this arm received the modified Bu/Cy conditioning regimen intensified by Ruxolitinib and Chidamide. The conditioning regimen for allogeneic hematopoietic stem cell transplantation consist of ruxolitinib (35 mg bid \[p.o.\], days -15 to -10, diminishing to day -1), chidamide (30 mg/day, twice per week from days -15 to -2), cytarabine (4g/m2/day, days -10 to -9), busulfan (0.8mg/kg, Q6h, days -8 to -6), cyclophosphamide (1.8 g/m2/day, days -5 to -4), carmustine(BCNU) (250mg/m2/day, day -3)

Drug: Modified By/Cy conditioning regimen intensified by Ruxolitinib and Chidamide

Interventions

Modified By/Cy conditioning regimen intensified by Ruxolitinib and Chidamide DRUG

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 (only for Haploidentical and unrelated donor), 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;

Also known as: Ruxolitinib and Chidamide

Ruxolitinib combined with Chidamide

Eligibility Criteria

• Age: 12 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• high risk Acute T cell Lymphoblast leukemia/ lymphoblastic lymphoma with the indications for allogeneic transplantation;
• Have haploidentical donors
• All patients should aged 12 to 65 years;
• Liver function: ALT and AST≤2.5 times the upper limit of normal , bilirubin≤2 times the upper limit of normal;
• Renal function: creatinine ≤the upper limit of normal;
• Patients without any uncontrolled infections , without organ dysfunction or without severe mental illness;
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2;
• Have signed informed consent.

You may not qualify if:

• pregnant women;
• Patients with mental illness or other states unable to comply with the protocol;

Sponsors & Collaborators

• Chinese PLA General Hospital: lead

Study Sites (1)

Chinese PLA General Hospital

Beijing, Beijing Municipality, 100853, China

RECRUITING

Related Publications (6)

• Ferrante F, Giaimo BD, Bartkuhn M, Zimmermann T, Close V, Mertens D, Nist A, Stiewe T, Meier-Soelch J, Kracht M, Just S, Kloble 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.

  PMID: 32107550 BACKGROUND

• 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.

  PMID: 25645356 BACKGROUND

• 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.

  PMID: 28484265 BACKGROUND

• 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.

  PMID: 28298231 BACKGROUND

• Stumpel DJ, Schneider P, Seslija L, Osaki H, Williams O, Pieters R, Stam RW. Connectivity mapping identifies HDAC inhibitors for the treatment of t(4;11)-positive infant acute lymphoblastic leukemia. Leukemia. 2012 Apr;26(4):682-92. doi: 10.1038/leu.2011.278. Epub 2011 Oct 21.

  PMID: 22015773 BACKGROUND

• Lato MW, Przysucha A, Grosman S, Zawitkowska J, Lejman M. The New Therapeutic Strategies in Pediatric T-Cell Acute Lymphoblastic Leukemia. Int J Mol Sci. 2021 Apr 26;22(9):4502. doi: 10.3390/ijms22094502.

  PMID: 33925883 BACKGROUND

MeSH Terms

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide; ruxolitinib

Study Officials

• Daihong Liu

  Chinese PLA General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daihong Liu

CONTACT

86-13681171597; daihongrm@163.com

Liping Dou

CONTACT

96-13681207138; lipingruirui@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: October 13, 2021
• Study Start: November 1, 2021
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2025
• Last Updated: December 14, 2021

Record last verified: 2021-12

Locations

CN (1)