ClinicalTrials.gov
ClinicalTrials.gov Menu

Precision Diagnosis Directing HDACi and TKI Target Therapy for Adult Ph-like ALL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03564470
Recruitment Status : Recruiting
First Posted : June 20, 2018
Last Update Posted : June 20, 2018
Sponsor:
Information provided by (Responsible Party):
Qifa Liu, Nanfang Hospital of Southern Medical University

Brief Summary:
Ph-like 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, two-arm, multi-site trial PDT-Ph-like-ALL is aimed to evaluate the safety and effect of oral histone deacetylase inhibitor chidamide and dasatinib for adult Ph-like ALL.

Condition or disease Intervention/treatment Phase
Leukemia Leukemia, Acute Leukemia, Lymphoblastic Leukemia, B-cell Drug: Chidamide Drug: Dasatinib Phase 2 Phase 3

Detailed Description:

Ph-like, or BCR-ABL1-like lymphoblastic leukemia is neoplasm of lymphoblasts committed to the B-cell lineage that lack the BCR-ABL1 translocation but show a pattern of the expression very similar to that seen in BCR-ABL1-positive ALL. 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, two-arm, multi-site trial is aimed to evaluate the safety and effect of oral histone deacetylase inhibitor (HDACi) chidamide and tyrosine kinase inhibitor (TKI) dasatinib for adult Ph-like ALL/LBL. HDACi chidamide and TKI dasatinib will be added to chidamide and dasatinib group, respectively, 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 is event-free survival and secondary study endpoints are complete remission and MRD after induction, adverse event and overall survival.

Pretreatment: Dexamethasone, -3 to 0d;

Chidamide for chidamide arm: 10mg/d, po qd.

Dasatinib for Dasatinib arm: 100mg/d, po qd.

Induction:VCR: 1, 8, 15, 22; IDA: 1, 8; CTX: 1g/m2, 1; PEG-asp: 2000-2500IU/m2, 1, 15; Pred: 1-24;

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

VLCAM (MRD1/d14>1%): CTX, d25; AraC 50mg/m2, d25-31, 26; 6-MP: 25-31, PEG-asp: 26;

Consolidation Module:

CM1: AraC 2g/m2, q12h, 1-2, Dex: 10mg/m2, 1-2, PEG-asp: 2, 6-MP: 1-7. IT: d1; CM2: MTX 3g/m2, 1, Dex: 10mg/m2, 1-2, PEG-asp: 2; 6-MP: 1-7; IT: d1; CM3: CTX 0.5g/m2, 1-3, PEG-asp: 2, 6-MP: 1-7, IT: d1.

Allo-HSCT: after CM3 when donors available. Non-HSCT: finish CM 4-9 and POMP maintenance.

CM4-6: repeat CM1-3. Re-Induction: after CM6. CM7-9: repeat CM1-3.

Maintenance: POMP-Pred: x12m; VCR x12m; MTX: x24m; 6-MPx24m.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, One-Arm, Multi-Site Trial of Precision Diagnosis Directing Target Total Therapy for Adult Ph-like Acute Lymphoblastic Leukemia
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
Drug Information available for: Dasatinib

Arm Intervention/treatment
Experimental: Chidamide
Chidamide will be added to chidamide arm Ph-like ALL(CRLF2 high-expression, CRLF2/EPO/JAK2 rearrangement, JAK/IL-7R/SH2B3 mutation, etc).
Drug: Chidamide
Chidamide will be administrated at dose of 10mg/day in chidamide arm in PDT-Ph-Like protocol. PDT-Ph-Like protocol for chidamide arm consists of diagnostic test (bone marrow aspiration, flow immunophenotyping, karyotyping,FISH, NGS, Flow-MRD), induction regimen (chidamide, prednisone, vincristine, cyclophosphamide, idarubicin, pegaspargase), consolidation regimen (chidamide, cytarabine, methotrexate, dexamethasone, cyclophosphamide, etoposide, 6-mercaptopurine, pegaspargase), MRD assessment and maintenance regimen, intrathecal injection chemotherapy, radiation therapy for CNS-involved leukemia and allogeneic hematopoietic stem cell transplantation.
Other Name: HDACi chidamide

Experimental: Dasatinib
Dasatinib at a dose of 100mg/day will be added to Dasatinib arm of Ph-like ALL (CRKL high-expression, ABL1 or ABL2 or CSFR1 or PRGFRB rearrangement, etc).
Drug: Dasatinib
Dasatinib will be administrated at a dose of 100mg/day in dasatinib arm in PDT-Ph-Like protocol. PDT-Ph-Like protocol for dasatinib arm consists of diagnostic test (bone marrow aspiration, flow immunophenotyping, karyotyping,FISH, NGS, Flow-MRD), induction regimen (dasatinib, prednisone, vincristine, cyclophosphamide, idarubicin, pegaspargase), consolidation regimen (dasatinib, cytarabine, methotrexate, dexamethasone, cyclophosphamide, etoposide, 6-mercaptopurine, pegaspargase), MRD assessment and maintenance regimen, intrathecal injection chemotherapy, radiation therapy for CNS-involved leukemia and allogeneic hematopoietic stem cell transplantation.
Other Name: TKI dasatinib




Primary Outcome Measures :
  1. Event free survival [ Time Frame: 3 years ]
    EFS of Ph-like ALL group


Secondary Outcome Measures :
  1. Minimum residual disease after induction [ Time Frame: 3 months ]
    MRD after 1 course

  2. CR after Induction Therapy [ Time Frame: 3 months ]
    CR rate of Ph-like group

  3. Death in induction [ Time Frame: 3 months ]
  4. Adverse events [ Time Frame: 3 years ]
    AE during PDT-Ph-like

  5. Relapse [ Time Frame: 3 years ]
    Relapse of Ph-like ALL

  6. Relapse free survival [ Time Frame: 3 years ]
    RFS

  7. Overall survival [ Time Frame: 3 years ]
    OS



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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;
  • Ph-like 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-Ph-like-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): NCT03564470


Contacts
Contact: Hongshengq Zhou, MD, Ph.D 86-20-62787349 zhs1@i.smu.edu.cn

Locations
China, Guangdong
Department of Hematology, Nanfang Hospital Recruiting
Guangzhou, Guangdong, China, 510515
Contact: Hongsheng Zhou, PhD, MD    86-20-62787349    zhs1@i.smu.edu.cn   
Sponsors and Collaborators
Nanfang Hospital of Southern Medical University

Responsible Party: Qifa Liu, M.D., Professor, Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier: NCT03564470     History of Changes
Other Study ID Numbers: PDT-Ph-Like
First Posted: June 20, 2018    Key Record Dates
Last Update Posted: June 20, 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

Keywords provided by Qifa Liu, Nanfang Hospital of Southern Medical University:
Acute Lymphoblastic Leukemia
Ph-like
Tyrosine Kinase Inhibitor
Histone Deacetylase Inhibitor

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, B-Cell
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dasatinib
6-Mercaptopurine
Histone Deacetylase Inhibitors
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Nucleic Acid Synthesis Inhibitors