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

June 11, 2018 updated by: Qifa Liu, Nanfang Hospital of Southern Medical University

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

70

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Hongsheng Zhou, MD, Ph.D
  • Phone Number: +862062787349
  • Email: zhs1@i.smu.edu.cn

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510515
        • Recruiting
        • Nanfang Hospital, Southern Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 55 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / 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 Names:
  • HDACi chidamide
Drug: Dexamethasone
Dexamethasone will be added in Pre-phase Regimen, Induction-Regimen, Consolidation-Module of PDT-ETP-ALL protocol.
Other Names:
  • DXM
Drug: vincristine
Vincristine will be added to Induction-Regimen, Consolidation-Module and Maintenance-Module of PDT-ETP-ALL protocol.
Other Names:
  • VCR
Drug: Cyclophosphamide
CTX will be added to Induction-Regimen, Consolidation-Module and Maintenance-Module of PDT-ETP-ALL protocol.
Other Names:
  • CTX
Drug: Idarubicin
IDA will be added to Induction-Regimen and Consolidation-Module of PDT-ETP-ALL protocol.
Other Names:
  • IDA
Drug: Pegaspargase
PEG-ASP will be added to Induction-Regimen and Consolidation-Module of PDT-ETP-ALL protocol.
Other Names:
  • PEG-ASP
Drug: Adriamycin
Adriamycin will be added to Consolidation-Module of PDT-ETP-ALL protocol.
Other Names:
  • ADR
Drug: Methotrexate
Methotrexate will be added to consolidation module of PDT-ETP-ALL protocol.
Other Names:
  • MTX
Drug: 6-Mercaptopurine
Mercaptopurine will be added to Consolidation-Module and Maintenance-Module of PDT-ETP-ALL protocol.
Other Names:
  • 6-MP
Drug: Etoposide
VP-16 will be added to Consolidation-Module of PDT-ETP-ALL protocol.
Other Names:
  • VP-16
Drug: Cytarabine
AraC will be added to Consolidation-Module of PDT-ETP-ALL protocol.
Other Names:
  • AraC
Procedure: Bone marrow aspiration
Bone marrow aspiration and additional tests will be performed in all module of PDT-ETP-ALL protocol.
Other Names:
  • BM test
Procedure: Intrathecal injection
Intrathecal injection chemotherapy will be performed in PDT-ETP-ALL protocol.
Other Names:
  • IT
Radiation: Radiation therapy
Radiation therapy will be performed for mediastinum and/or central nervous system leukemia in PDT-ETP-ALL protocol.
Other Names:
  • 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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Event free survival
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 3 years
3 years
Adverse events
Time Frame: 3 years
3 years
Minimum residual disease after induction
Time Frame: 3 months
3 months
CR after Induction Therapy
Time Frame: 3 years
3 years
Death in induction
Time Frame: 3 month
3 month
Relapse
Time Frame: 3 years
3 years
Relapse free survival
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nanfang Hospital of Southern Medical University

Investigators

  • Study Director: Hongsheng Zhou, MD, PhD, Nanfang Hospital, Southern Medical University, China

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 14, 2016

Primary Completion (ANTICIPATED)

May 30, 2020

Study Completion (ANTICIPATED)

August 30, 2020

Study Registration Dates

First Submitted

April 21, 2018

First Submitted That Met QC Criteria

June 11, 2018

First Posted (ACTUAL)

June 12, 2018

Study Record Updates

Last Update Posted (ACTUAL)

June 12, 2018

Last Update Submitted That Met QC Criteria

June 11, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PDT-ETP-ALL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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