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

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ClinicalTrials.gov Identifier: NCT03564704
Recruitment Status : Recruiting
First Posted : June 21, 2018
Last Update Posted : June 21, 2018
Sponsor:
Information provided by (Responsible Party):
Qifa Liu, Nanfang Hospital of Southern Medical University

Brief 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.

Condition or disease Intervention/treatment Phase
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

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
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
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.
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




Primary Outcome Measures :
  1. Event-Free-Survival [ Time Frame: 3 years ]
    3 years EFS of LBL/ALL patients enrolled in PDT-ALL-LBL


Secondary Outcome Measures :
  1. Minimum residual disease after induction [ Time Frame: 3 months ]
    MRD after induction regimen of PDT-ALL-LBL protocol

  2. CR after Induction Therapy [ Time Frame: 3 months ]
    CR after induction regimen of PDT-ALL-LBL protocol

  3. Death in induction [ Time Frame: 3 months ]
    Dearth during induction regimen of PDT-ALL-LBL

  4. Adverse events [ Time Frame: 3 years ]
    AE of 3 years of LBL patients enrolled in PDT-ALL-LBL

  5. Relapse [ Time Frame: 3 years ]
    Cumulative incidence relapse rate of 3 years of LBL patients enrolled in PDT-ALL-LBL protocol

  6. Relapse free survival [ Time Frame: 3 years ]
    3 years RFS of LBL patients enrolled in PDT-ALL-LBL protocol

  7. 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
Criteria

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.

Information from the National Library of Medicine

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


Contacts
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Contact: Hongsheng Zhou +862062787349 zhs1@i.smu.edu.cn

Locations
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China, Guangdong
Department of Hematology, Nanfang Hospital Recruiting
Guangzhou, Guangdong, China, 510515
Contact: Hongsheng Zhou    +862062787349    zhs1@i.smu.edu.cn   
Sponsors and Collaborators
Nanfang Hospital of Southern Medical University
Investigators
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Study Chair: Qifa Liu, MD Department of Hematology Nanfang Hospital

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Responsible Party: Qifa Liu, M.D., Professor, Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier: NCT03564704     History of Changes
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

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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

Additional relevant MeSH terms:
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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
Dexamethasone
Dexamethasone acetate
Cyclophosphamide
Methotrexate
Etoposide
Etoposide phosphate
Cytarabine
Vincristine
Doxorubicin
Liposomal doxorubicin
Idarubicin
Mercaptopurine
Pegaspargase
BB 1101
Histone Deacetylase Inhibitors
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents