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

NCT ID: NCT05075681

Last Updated: 2021-12-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE1/PHASE2

Total Enrollment

50 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-01

Study Completion Date

2025-06-01

Brief Summary

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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.

Detailed Description

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Haploidenticl Peripheral blood Stem Cell Transplantation should be offered to eligible patients with Acute T cell Lymphoblast leukemia/ lymphoblastic lymphoma whenever feasible. To further improve the outcome of transplantation patients with Acute T cell Lymphoblast leukemia/ lymphoblastic lymphoma, 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 T cell Lymphoblast leukemia/ lymphoblastic lymphoma undergoing allogeneic peripheral blood stem cell transplantation.

Conditions

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Peripheral Blood Stem Cell Transplantation

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Ruxolitinib combined with Chidamide

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)

Group Type EXPERIMENTAL

Modified By/Cy conditioning regimen intensified by Ruxolitinib and Chidamide

Intervention Type 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;

Interventions

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Modified By/Cy conditioning regimen intensified by Ruxolitinib and 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 (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;

Intervention Type DRUG

Other Intervention Names

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Ruxolitinib and Chidamide

Eligibility Criteria

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Inclusion Criteria

1. high risk Acute T cell Lymphoblast leukemia/ lymphoblastic lymphoma with the indications for allogeneic transplantation;
2. Have 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;
Minimum Eligible Age

12 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Chinese PLA General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Daihong Liu

Director

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Daihong Liu

Role: PRINCIPAL_INVESTIGATOR

Chinese PLA General Hospital

Locations

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Chinese PLA General Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Daihong Liu

Role: CONTACT

Phone: 86-13681171597

Email: [email protected]

Liping Dou

Role: CONTACT

Phone: 96-13681207138

Email: [email protected]

Facility Contacts

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Jiang Cao

Role: primary

References

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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.

Reference Type BACKGROUND
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Reference Type BACKGROUND
PMID: 25645356 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28484265 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28298231 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22015773 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33925883 (View on PubMed)

Other Identifiers

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S-2020-483-01

Identifier Type: -

Identifier Source: org_study_id