Precision Diagnosis Directing HDACi Chidamide Target Therapy for Adult T-LBL/ALL
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ClinicalTrials.gov Identifier: NCT03564704 |
Recruitment Status : Unknown
Verified June 2018 by Qifa Liu, Nanfang Hospital, Southern Medical University.
Recruitment status was: Recruiting
First Posted : June 21, 2018
Last Update Posted : June 21, 2018
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Condition or disease | Intervention/treatment | Phase |
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Leukemia Leukemia, Acute Adult Lymphoblastic Lymphoma Leukemia, Lymphoblastic Leukemia, T Cell Adult Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Lymphoblastic Leukemia | Drug: Dexamethasone Drug: vincristine Drug: Cyclophosphamide Drug: Idarubicin Drug: Pegaspargase Drug: Adriamycin Drug: Methotrexate Drug: 6-mercaptopurine. Drug: Etoposide Drug: Cytarabine Procedure: Bone marrow aspiration Procedure: Intrathecal injection Radiation: Radiation therapy Genetic: NGS Procedure: allogeneic hematopoietic stem cell transplantation Diagnostic Test: Flow-MRD Diagnostic Test: FISH Diagnostic Test: Flow immunophenotyping Diagnostic Test: Karyotyping Drug: Chidamide Diagnostic Test: PET-CT scan | Phase 2 Phase 3 |
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.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 80 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | February 14, 2016 |
Estimated Primary Completion Date : | May 30, 2021 |
Estimated Study Completion Date : | May 30, 2021 |
Arm | Intervention/treatment |
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Experimental: PDT-ALL-LBL
The intervention of PDT-ALL-LBL consists of diagnostic test (bone marrow aspiration, flow immunophenotyping, karyotyping,FISH, NGS, Flow-MRD, PET-CT scan), induction regimen (chidamide, dexamethasone, vincristine, cyclophosphamide, idarubicin, pegaspargase), consolidation regimen (chidamide, prednisone, cytarabine, methotrexate, cyclophosphamide, etoposide, adriamycin, 6-mercaptopurine, pegaspargase), MRD assessment and maintenance regimen (chidamide, prednisone, vincristine, methotrexate, 6-mercaptopurine), intrathecal injection chemotherapy (methotrexate, cytarabine, dexamethasone), radiation therapy (for mediastinum- and/or central nervous system-involved lymphoma/leukemia) and allogeneic hematopoietic stem cell transplantation for patients with donor.
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Drug: Dexamethasone
Dexamethasone will be added in Pre-phase Regimen, Induction-Regimen, Consolidation-Module of PDT-ALL-LBL protocol.
Other Name: DXM Drug: vincristine Vincristine will be added to Induction-Regimen, Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
Other Name: VCR Drug: Cyclophosphamide CTX will be added to Induction-Regimen, Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
Other Name: CTX Drug: Idarubicin IDA will be added to Induction-Regimen and Consolidation-Module of PDT-ALL-LBL protocol.
Other Name: IDA Drug: Pegaspargase PEG-ASP will be added to Induction-Regimen and Consolidation-Module of PDT-ALL-LBL protocol.
Other Name: PEG-ASP Drug: Adriamycin Adriamycin will be added to Consolidation-Module of PDT-ALL-LBL protocol.
Other Name: ADR Drug: Methotrexate Methotrexate will be added to Consolidation-Module of PDT-ALL-LBL protocol.
Other Name: MTX Drug: 6-mercaptopurine. Mercaptopurine will be added to Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
Other Name: 6-MP Drug: Etoposide VP-16 will be added to Consolidation-Module of PDT-ALL-LBL protocol.
Other Name: VP-16 Drug: Cytarabine AraC will be added to Consolidation-Module of PDT-ALL-LBL protocol.
Other Name: AraC Procedure: Bone marrow aspiration Bone marrow aspiration and additional tests will be performed in all module of PDT-ALL-LBL protocol.
Other Name: BM smear Procedure: Intrathecal injection Intrathecal injection of chemotherapy will be performed in PDT-ALL-LBL protocol.
Other Name: IT Radiation: Radiation therapy Radiation therapy will be performed for mediastinum and/or central nervous system leukemia/lymphoma in PDT-ALL-LBL protocol.
Other Name: RT 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.
Other Name: Allo-HSCT 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.
Other Name: HDACi Chidamide Diagnostic Test: PET-CT scan PET-scan will be performed for T-LBL patients for MRD assessment in PDT-ALL-LBL.
Other Name: PET-CT |
- Event-Free-Survival [ Time Frame: 3 years ]3 years EFS of LBL/ALL patients enrolled in PDT-ALL-LBL
- Minimum residual disease after induction [ Time Frame: 3 months ]MRD after induction regimen of PDT-ALL-LBL protocol
- CR after Induction Therapy [ Time Frame: 3 months ]CR after induction regimen of PDT-ALL-LBL protocol
- Death in induction [ Time Frame: 3 months ]Dearth during induction regimen of PDT-ALL-LBL
- Adverse events [ Time Frame: 3 years ]AE of 3 years of LBL patients enrolled in PDT-ALL-LBL
- Relapse [ Time Frame: 3 years ]Cumulative incidence relapse rate of 3 years of LBL patients enrolled in PDT-ALL-LBL protocol
- Relapse free survival [ Time Frame: 3 years ]3 years RFS of LBL patients enrolled in PDT-ALL-LBL protocol
- Overall survival [ Time Frame: 3 years ]3 years OS of LBL patients enrolled in PDT-ALL-LBL protocol
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Ages Eligible for Study: | 14 Years to 55 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03564704
Contact: Hongsheng Zhou | +862062787349 | zhs1@i.smu.edu.cn |
China, Guangdong | |
Department of Hematology, Nanfang Hospital | Recruiting |
Guangzhou, Guangdong, China, 510515 | |
Contact: Hongsheng Zhou +862062787349 zhs1@i.smu.edu.cn |
Study Chair: | Qifa Liu, MD | Department of Hematology Nanfang Hospital |
Responsible Party: | Qifa Liu, M.D., Professor, Nanfang Hospital, Southern Medical University |
ClinicalTrials.gov Identifier: | NCT03564704 |
Other Study ID Numbers: |
PDT-ALL-LBL |
First Posted: | June 21, 2018 Key Record Dates |
Last Update Posted: | June 21, 2018 |
Last Verified: | June 2018 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Product Manufactured in and Exported from the U.S.: | No |
Lymphoma Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Lymphoma, Non-Hodgkin Leukemia, T-Cell Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Hematologic Diseases Cytarabine Dexamethasone |
Cyclophosphamide Methotrexate Etoposide Vincristine Doxorubicin Mercaptopurine Idarubicin Pegaspargase Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action |