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Precision Diagnosis Directing HDACi Chidamide Target Therapy for Adult ETP-ALL

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ClinicalTrials.gov Identifier: NCT03553238
Recruitment Status : Recruiting
First Posted : June 12, 2018
Last Update Posted : June 12, 2018
Sponsor:
Information provided by (Responsible Party):
Qifa Liu, Nanfang Hospital of Southern Medical University

Brief Summary:
ETP-ALL is a recently recognized high-risk subgroup and the optimal therapeutic approaches are poorly characterized. Based on the pediatric-inspired, PEG-L-asparaginase-intensified and MRD-directed PDT-ALL-2016 protocol, this open-label, one-arm, multi-site trial is aimed to evaluate the safety and effect of a novel oral histone deacetylase inhibitor chidamide for adult ETP-ALL/LBL in CHINA.

Condition or disease Intervention/treatment Phase
Leukemia, Acute Leukemia, T Cell Leukemia, Lymphoblastic Drug: Chidamide 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 Phase 2 Phase 3

Detailed Description:

Early T-cell precursor (ETP) lymphoblastic leukemia (ETP-ALL) is a neoplasm composed of cells committed to the T-cell lineage but with an unique immunophenotype indicating only limited early T differentiation. In the highly orchestrated development of T cell fate specification under physiological condition, the most immature early thymic progenitors (ETPs) retain multilineage potentials. ETP-ALL blasts have a characteristic immunophenotype, with reduced/absent expression of T-lymphoid markers CD1a, CD5, CD8; and positivity for at least one HSC and/or myeloid antigen CD34, CD117, HLA-DR, CD13, CD33, CD11b, CD65. Recent study shed light on the genetic landscape of adult ETP-ALL, which revealed that more than 40% adult ETP-ALL harbored histone modification mutations. Chidamide is a novel oral HDACi with promising activity in non-Hodgkin lymphoma (NHL). Based on the pediatric-inspired, PEG-L-asparaginase-intensified and MRD-directed PDT-ALL-2016 protocol, this open-label, one-arm, multi-site trial is aimed to evaluate the safety and effect of a novel oral histone deacetylase inhibitor chidamide for adult ETP-ALL/LBL. HDACi chidamide at a dose of 10mg/day will be added to ETP-ALL group from induction therapy to consolidation therapy (total courses of chidamide treatment: 5 courses for allo-HSCT after Consolidation Module-3; 12 courses for patients non-allo-HSCT after Consolidation Module 1-9). Primary study endpoint of PDT-ETP-ALL is event-free survival of ETP-ALL group and secondary study endpoints are complete remission and MRD after induction, adverse event and overall survival of ETP-ALL group.

Pretreatment: Dexamethasone, -3 to 0d;

Induction:VCR: 1, 8, 15, 22; IDA: 1, 8; CTX: 1g/m2, 1, 8; PEG-asp: 2000-2500IU/m2, 1, 15; Dex: 1-24, chidamide: 10mg/d, po, qd.

MRD: d14, 24, 45, and pre-allo-HSCT.

VLCAM (MRD1/d14>1%): CTX, d25; AraC 2g/m2, q12h, d25, 26; 6-MP: 25-31, PEG-asp: 26; chidamide: 10mg/d, po, qd.

Consolidation Module:

CM-1: AraC 3g/m2, q12h, 1-2, Dex: 10mg/m2, 1-2, PEG-asp: 2, 6-MP: 1-7. IT: d1, chidamide: 10mg/d, po, qd.

CM-2: MTX 5g/m2, 1, Dex: 10mg/m2, 1-2, PEG-asp: 2; 6-MP: 1-7; IT: d1; chidamide: 10mg/d, po, qd.

CM-3: CTX 0.5g/m2, 1-3, PEG-asp: 2, Doxorubicin: 40mg/m2, 4, 6-MP: 1-7, IT: d1;chidamide: 10mg/d, po, qd.

Allo-HSCT: after CM-3 when donors available. Non-HSCT: finish CM 4-9 and POMP maintenance.

CM 4-6: repeat CM 1-3. Re-Induction: after CM-6. CM 7-9: repeat CM1-3.

Maintenance: CPOMP-chidamide 10mg/d, po, qd; Pred for 12 months; VCR for 12 months; MTX for 24 months; 6-MP for 24 months.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 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 Target Total Therapy for Adult Early T-cell Progenitor Acute Lymphoblastic Leukemia/Lymphoma
Actual Study Start Date : February 14, 2016
Estimated Primary Completion Date : May 30, 2020
Estimated Study Completion Date : August 30, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
Experimental: ETP-ALL
Chidamide at a dose of 10mg/day will be added to PDT-ETP-ALL protocol. The intervention of PDT-ETP-ALL 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, radiation therapy (for mediastinum- and/or central nervous system-involved lymphoma/leukemia) and allogeneic hematopoietic stem cell transplantation for patients with donor.
Drug: Chidamide
Chidamide will be administrated at a dose of 10mg/day in PDT-ETP-ALL protocol.
Other Name: HDACi chidamide

Drug: Dexamethasone
Dexamethasone will be added in Pre-phase Regimen, Induction-Regimen, Consolidation-Module of PDT-ETP-ALL protocol.
Other Name: DXM

Drug: vincristine
Vincristine will be added to Induction-Regimen, Consolidation-Module and Maintenance-Module of PDT-ETP-ALL protocol.
Other Name: VCR

Drug: Cyclophosphamide
CTX will be added to Induction-Regimen, Consolidation-Module and Maintenance-Module of PDT-ETP-ALL protocol.
Other Name: CTX

Drug: Idarubicin
IDA will be added to Induction-Regimen and Consolidation-Module of PDT-ETP-ALL protocol.
Other Name: IDA

Drug: Pegaspargase
PEG-ASP will be added to Induction-Regimen and Consolidation-Module of PDT-ETP-ALL protocol.
Other Name: PEG-ASP

Drug: Adriamycin
Adriamycin will be added to Consolidation-Module of PDT-ETP-ALL protocol.
Other Name: ADR

Drug: Methotrexate
Methotrexate will be added to consolidation module of PDT-ETP-ALL protocol.
Other Name: MTX

Drug: 6-Mercaptopurine
Mercaptopurine will be added to Consolidation-Module and Maintenance-Module of PDT-ETP-ALL protocol.
Other Name: 6-MP

Drug: Etoposide
VP-16 will be added to Consolidation-Module of PDT-ETP-ALL protocol.
Other Name: VP-16

Drug: Cytarabine
AraC will be added to Consolidation-Module of PDT-ETP-ALL protocol.
Other Name: AraC

Procedure: Bone marrow aspiration
Bone marrow aspiration and additional tests will be performed in all module of PDT-ETP-ALL protocol.
Other Name: BM test

Procedure: Intrathecal injection
Intrathecal injection chemotherapy will be performed in PDT-ETP-ALL protocol.
Other Name: IT

Radiation: Radiation therapy
Radiation therapy will be performed for mediastinum and/or central nervous system leukemia in PDT-ETP-ALL protocol.
Other Name: RT

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

Procedure: allogeneic hematopoietic stem cell transplantation
Allo-HSCT will be performed for patients with available donor in PDT-ETP-ALL protocol.
Other Name: allo-HSCT

Diagnostic Test: Flow-MRD
Flow-MRD will be added to PDT-ETP-ALL for bone marrow and cerebrospinal fluid samples.

Diagnostic Test: FISH
FISH will be performed in PDT-ETP-ALL for bone marrow samples.

Diagnostic Test: Flow immunophenotyping
Flow immunophenotyping will be performed in PDT-ETP-ALL protocol.

Diagnostic Test: Karyotyping
Karyotyping will be performed in PDT-ETP-ALL protocol.




Primary Outcome Measures :
  1. Event free survival [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Minimum residual disease after induction [ Time Frame: 3 months ]
  2. CR after Induction Therapy [ Time Frame: 3 years ]
  3. Death in induction [ Time Frame: 3 month ]
  4. Adverse events [ Time Frame: 3 years ]
  5. Relapse [ Time Frame: 3 years ]
  6. Relapse free survival [ Time Frame: 3 years ]
  7. Overall survival [ Time Frame: 3 years ]


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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;
  • ETP-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-ETP-ALL.

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): NCT03553238


Contacts
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Contact: Hongsheng Zhou, MD, Ph.D +862062787349 zhs1@i.smu.edu.cn

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

Publications:
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Responsible Party: Qifa Liu, M.D., Professor, Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier: NCT03553238     History of Changes
Other Study ID Numbers: PDT-ETP-ALL
First Posted: June 12, 2018    Key Record Dates
Last Update Posted: June 12, 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
Keywords provided by Qifa Liu, Nanfang Hospital of Southern Medical University:
Early T-cell Precursor
Acute Lymphoblastic Leukemia
Histone Deacetylase Inhibitor
Chidamide
Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, T-Cell
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Dexamethasone
Dexamethasone acetate
Cyclophosphamide
Methotrexate
Etoposide
Vincristine
Doxorubicin
Liposomal doxorubicin
Idarubicin
Mercaptopurine
Pegaspargase
BB 1101
Histone Deacetylase Inhibitors
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents