Precision Diagnosis Directing HDACi Chidamide Target Therapy for Adult T-LBL/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 Total Therapy for Adult T-lymphoblastic Lymphoma/Leukemia

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

80

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

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510515
        • Recruiting
        • Department of Hematology, Nanfang Hospital
        • 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 (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • DXM
Drug: vincristine
Vincristine will be added to Induction-Regimen, Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
Other Names:
  • VCR
Drug: Cyclophosphamide
CTX will be added to Induction-Regimen, Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
Other Names:
  • CTX
Drug: Idarubicin
IDA will be added to Induction-Regimen and Consolidation-Module of PDT-ALL-LBL protocol.
Other Names:
  • IDA
Drug: Pegaspargase
PEG-ASP will be added to Induction-Regimen and Consolidation-Module of PDT-ALL-LBL protocol.
Other Names:
  • PEG-ASP
Drug: Adriamycin
Adriamycin will be added to Consolidation-Module of PDT-ALL-LBL protocol.
Other Names:
  • ADR
Drug: Methotrexate
Methotrexate will be added to Consolidation-Module of PDT-ALL-LBL protocol.
Other Names:
  • MTX
Drug: 6-mercaptopurine.
Mercaptopurine will be added to Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
Other Names:
  • 6-MP
Drug: Etoposide
VP-16 will be added to Consolidation-Module of PDT-ALL-LBL protocol.
Other Names:
  • VP-16
Drug: Cytarabine
AraC will be added to Consolidation-Module of PDT-ALL-LBL protocol.
Other Names:
  • AraC
Procedure: Bone marrow aspiration
Bone marrow aspiration and additional tests will be performed in all module of PDT-ALL-LBL protocol.
Other Names:
  • BM smear
Procedure: Intrathecal injection
Intrathecal injection of chemotherapy will be performed in PDT-ALL-LBL protocol.
Other Names:
  • IT
Radiation: Radiation therapy
Radiation therapy will be performed for mediastinum and/or central nervous system leukemia/lymphoma in PDT-ALL-LBL protocol.
Other Names:
  • 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 Names:
  • 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 Names:
  • HDACi Chidamide
Diagnostic test: PET-CT scan
PET-scan will be performed for T-LBL patients for MRD assessment in PDT-ALL-LBL.
Other Names:
  • PET-CT

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-Free-Survival
Time Frame: 3 years
3 years EFS of LBL/ALL patients enrolled in PDT-ALL-LBL
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Minimum residual disease after induction
Time Frame: 3 months
MRD after induction regimen of PDT-ALL-LBL protocol
3 months
CR after Induction Therapy
Time Frame: 3 months
CR after induction regimen of PDT-ALL-LBL protocol
3 months
Death in induction
Time Frame: 3 months
Dearth during induction regimen of PDT-ALL-LBL
3 months
Adverse events
Time Frame: 3 years
AE of 3 years of LBL patients enrolled in PDT-ALL-LBL
3 years
Relapse
Time Frame: 3 years
Cumulative incidence relapse rate of 3 years of LBL patients enrolled in PDT-ALL-LBL protocol
3 years
Relapse free survival
Time Frame: 3 years
3 years RFS of LBL patients enrolled in PDT-ALL-LBL protocol
3 years
Overall survival
Time Frame: 3 years
3 years OS of LBL patients enrolled in PDT-ALL-LBL protocol
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 Chair: Qifa Liu, MD, Department of Hematology Nanfang Hospital

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, 2021

Study Completion (Anticipated)

May 30, 2021

Study Registration Dates

First Submitted

June 11, 2018

First Submitted That Met QC Criteria

June 11, 2018

First Posted (Actual)

June 21, 2018

Study Record Updates

Last Update Posted (Actual)

June 21, 2018

Last Update Submitted That Met QC Criteria

June 11, 2018

Last Verified

June 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PDT-ALL-LBL

Drug and device information, study documents

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

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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