Trials / Unknown

UnknownNCT03564704

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

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

Status: Unknown
Phase: Phase 2 / Phase 3
Study type: Interventional
Enrollment: 80 (estimated)

Sponsor: Nanfang Hospital, Southern Medical University · Academic / Other
Sex: All
Age: 14 Years – 55 Years
Healthy volunteers: Not accepted

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.

Detailed 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.

Conditions

Interventions

Type	Name	Description
DRUG	Dexamethasone	Dexamethasone will be added in Pre-phase Regimen, Induction-Regimen, Consolidation-Module of PDT-ALL-LBL protocol.
DRUG	vincristine	Vincristine will be added to Induction-Regimen, Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
DRUG	Cyclophosphamide	CTX will be added to Induction-Regimen, Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
DRUG	Idarubicin	IDA will be added to Induction-Regimen and Consolidation-Module of PDT-ALL-LBL protocol.
DRUG	Pegaspargase	PEG-ASP will be added to Induction-Regimen and Consolidation-Module of PDT-ALL-LBL protocol.
DRUG	Adriamycin	Adriamycin will be added to Consolidation-Module of PDT-ALL-LBL protocol.
DRUG	Methotrexate	Methotrexate will be added to Consolidation-Module of PDT-ALL-LBL protocol.
DRUG	6-mercaptopurine.	Mercaptopurine will be added to Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
DRUG	Etoposide	VP-16 will be added to Consolidation-Module of PDT-ALL-LBL protocol.
DRUG	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.
PROCEDURE	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.
DIAGNOSTIC_TEST	FISH	FISH will be added to PDT-ALL-LBL for bone marrow samples.
DIAGNOSTIC_TEST	Flow immunophenotyping	Flow immunophenotyping will be performed in PDT-ALL-LBL protocol.
DIAGNOSTIC_TEST	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.

Timeline

Start date: 2016-02-14
Primary completion: 2021-05-30
Completion: 2021-05-30
First posted: 2018-06-21
Last updated: 2018-06-21

Locations

1 site across 1 country: China

Source: ClinicalTrials.gov record NCT03564704. Inclusion in this directory is not an endorsement.