Precision Diagnosis Directing HDACi Chidamide Target Therapy for Adult T-LBL/ALL

Leukemia Clinical Trial

Official title:

An Open-Label, One-Arm, Multi-Site Trial of Precision Diagnosis Directing Histone Deacetylase Inhibitor Chidamide Total Therapy for Adult T-lymphoblastic Lymphoma/Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03564704
• Other study ID #: PDT-ALL-LBL
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: February 14, 2016
• Est. completion date: May 30, 2021

Study information

• Verified date: June 2018
• Source: Nanfang Hospital of Southern Medical University
• Contact: Hongsheng Zhou
• Phone: +862062787349
• Email: zhs1[@]i.smu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Based on the pediatric-inspired, PEG-L-asparaginase-intensified and MRD-directed PDT-ALL-2016 protocol, this open-label, one-arm, multi-site trial PDT-ALL-LBL is aimed to evaluate the safety and effect of oral histone deacetylase inhibitor chidamide for adult T-ALL/LBL. Compared to PDT-ALL-2016 for B-ALL, HDACi chidamide will be administrated from induction therapy to maintenance therapy, along with higher dose of consolidation regimen of cytarabine, methotrexate, cyclophosphamide.

Description:

T-lymphoblastic lymphoma/leukemia is a neoplasm of lymphoblasts committed to the T-cell lineage, typically composed of small to medium-sized blast with scant cytoplasm, moderately condensed to dispersed chromatin, and inconspicuous nucleoli, involving bone marrow and blood or presenting with primary involvement of the thymus or of nodal or extranodal sites. T-ALL/LBL is generally considered a higher-risk disease than B-ALL. Compared to B-ALL, T-LBL/ALL is associated with a higher risk of induction failure, early relapse, and isolated CNS relapse.

Chidamide is a novel oral HDACi with promising activity in non-Hodgkin lymphoma (NHL). Chidamide, a new oral isotype-selective HDACi, approved in China for the treatment of R/R PTCL in December 2014. Based on the pediatric-inspired, PEG-L-asparaginase-intensified and MRD-directed PDT-ALL-2016 protocol, this open-label, two-arm, multi-site trial PDT-ALL-LBL is aimed to evaluate the safety and effect of oral histone deacetylase inhibitor chidamide for adult T-ALL/LBL. Compared to PDT-ALL-2016 for B-ALL, HDACi chidamide will be administrated from induction therapy to maintenance therapy, along with higher dose of consolidation regimen of cytarabine, methotrexate, cyclophosphamide.

The intervention of PDT-ALL-LBL consists of diagnostic test (bone marrow aspiration, flow immunophenotyping, karyotyping，FISH, NGS, Flow-MRD), induction regimen (chidamide, dexamethasone, vincristine, cyclophosphamide, Idarubicin, pegaspargase), consolidation regimen (chidamide, prednisone, cytarabine, methotrexate, cyclophosphamide, etoposide, adriamycin, 6-mercaptopurine, pegaspargase), MRD assessment (MRD1/d14, MRD2/d24, MRD3/d45, MRD4/pre-allo-HSCT) and maintenance regimen (chidamide, vincristine, methotrexate, 6-mercaptopurine), intrathecal injection, radiation therapy (for mediastinum- and/or central nervous system-involved lymphoma/leukemia) and allogeneic hematopoietic stem cell transplantation for patients with donor.

Induction Regimen-Pretreatment: dexamethasone, -3d to 0d; Induction regimen VICLD: VCR: d1, d8, d15, d22; IDA: d1, d8; CTX: 1g/m2, 1; PEG-asp: 2000-2500IU/m2, 1, 15; dexamethasone: 1-24; chidamide: 10mg/d, po, qd. Flow-based MRD assessment: d14, d24 during induction regimen, d45, and pre-HSCT. Salvage regimen VLCAM (MRD1/d24>1%): CTX, d25; AraC 50mg/m2, d25-31; 6-MP: 25-31, PEG-asp: 2500IU/m2, d26. Consolidation Module (CM)-CM1: AraC 3g/m2, q12h, d1-2, Dex: 10mg/m2, d1-2, PEG-asp: 2, 6-MP: d1-7, chidamide, po qd; CM2: MTX 5g/m2, 1, Dex: 10mg/m2, 1-2, PEG-asp: d2, 6-MP: 1-7, chidamide, po qd; CM3: CTX 1g/m2, 1-3, PEG-asp: 2, 6-MP: 1-7, chidamide, po qd. CM4-6: repeat CM 1-3. Re-Induction: VICLD after CM6. CM7-9: repeat CM1-3. Allo-HSCT: after CM3 when matched-related-donor (MRD), haploidentical related donor (HRD) or matched-unrelated-donor (MUD) available. Non-allo-HSCT: finish CM4-9 and CPOMP maintenance. Maintenance Module-CPOMP: chidamide, po qd for 24 months; Pred: for 12 months; VCR for 12 months; MTX: for 24m months; 6-MP for 24 months.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: May 30, 2021
• Est. primary completion date: May 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 14 Years to 55 Years

Eligibility

Inclusion Criteria:

• 14-55 years old;

• LBL/ALL newly diagnosed;

• signed written informed consent.

Exclusion Criteria:

• Pregnant women;

• History of pancreatitis;

• History of diabetes;

• History of active peptic ulcer disease in the past 6 months;

• History of arteriovenous thrombosis in the past 6 months;

• Severe active infection;

• Allergic to any drugs in PDT-ALL-LBL protocol.

Related Conditions & MeSH terms

• Adult Acute Lymphoblastic Leukemia
• Adult Lymphoblastic Lymphoma
• Leukemia
• Leukemia, Acute
• Leukemia, Lymphoblastic
• Leukemia, Lymphoid
• Leukemia, T Cell
• Leukemia, T-Cell
• Lymphoblastic Leukemia
• Lymphoblastic Lymphoma
• Lymphoma
• Lymphoma, Non-Hodgkin
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Dexamethasone
Dexamethasone will be added in Pre-phase Regimen, Induction-Regimen, Consolidation-Module of PDT-ALL-LBL protocol.
• vincristine
Vincristine will be added to Induction-Regimen, Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
• Cyclophosphamide
CTX will be added to Induction-Regimen, Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
• Idarubicin
IDA will be added to Induction-Regimen and Consolidation-Module of PDT-ALL-LBL protocol.
• Pegaspargase
PEG-ASP will be added to Induction-Regimen and Consolidation-Module of PDT-ALL-LBL protocol.
• Adriamycin
Adriamycin will be added to Consolidation-Module of PDT-ALL-LBL protocol.
• Methotrexate
Methotrexate will be added to Consolidation-Module of PDT-ALL-LBL protocol.
• 6-mercaptopurine.
Mercaptopurine will be added to Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
• Etoposide
VP-16 will be added to Consolidation-Module of PDT-ALL-LBL protocol.
• Cytarabine
AraC will be added to Consolidation-Module of PDT-ALL-LBL protocol.

Procedure:
• Bone marrow aspiration
Bone marrow aspiration and additional tests will be performed in all module of PDT-ALL-LBL protocol.
• Intrathecal injection
Intrathecal injection of chemotherapy will be performed in PDT-ALL-LBL protocol.

Radiation:
• Radiation therapy
Radiation therapy will be performed for mediastinum and/or central nervous system leukemia/lymphoma in PDT-ALL-LBL protocol.

Genetic:
• NGS
Next-Generation-Sequencing (NGS) will be performed in PDT-ALL-LBL protocol.

Procedure:
• allogeneic hematopoietic stem cell transplantation
Allo-HSCT will be added to LBL patients with available donor in PDT-ALL-LBL protocol.

Diagnostic Test:
• Flow-MRD
Flow-MRD will be added to PDT-ALL-LBL for bone marrow and cerebrospinal fluid samples.
• FISH
FISH will be added to PDT-ALL-LBL for bone marrow samples.
• Flow immunophenotyping
Flow immunophenotyping will be performed in PDT-ALL-LBL protocol.
• Karyotyping
Karyotyping will be performed in PDT-ALL-LBL protocol.

Drug:
• Chidamide
HDACi chidamide will be added to induction regimen, consolidation and maintenance module of PDT-ALL-LBL.

Diagnostic Test:
• PET-CT scan
PET-scan will be performed for T-LBL patients for MRD assessment in PDT-ALL-LBL.

Locations

Country	Name	City	State
China	Department of Hematology, Nanfang Hospital	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-Free-Survival	3 years EFS of LBL/ALL patients enrolled in PDT-ALL-LBL	3 years
Secondary	Minimum residual disease after induction	MRD after induction regimen of PDT-ALL-LBL protocol	3 months
Secondary	CR after Induction Therapy	CR after induction regimen of PDT-ALL-LBL protocol	3 months
Secondary	Death in induction	Dearth during induction regimen of PDT-ALL-LBL	3 months
Secondary	Adverse events	AE of 3 years of LBL patients enrolled in PDT-ALL-LBL	3 years
Secondary	Relapse	Cumulative incidence relapse rate of 3 years of LBL patients enrolled in PDT-ALL-LBL protocol	3 years
Secondary	Relapse free survival	3 years RFS of LBL patients enrolled in PDT-ALL-LBL protocol	3 years
Secondary	Overall survival	3 years OS of LBL patients enrolled in PDT-ALL-LBL protocol	3 years