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

NCT ID: NCT03564470

Last Updated: 2022-07-01

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-14
• Study Completion Date: 2023-08-30

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.

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.

Conditions

Leukemia; Leukemia, Acute; Leukemia, Lymphoblastic; Leukemia, B-cell

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Chidamide

Chidamide will be added to chidamide arm Ph-like ALL(CRLF2 high-expression, CRLF2/EPO/JAK2 rearrangement, JAK/IL-7R/SH2B3 mutation, etc).

Group Type: EXPERIMENTAL

Chidamide

Intervention Type: DRUG

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.

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).

Group Type: EXPERIMENTAL

Dasatinib

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

HDACi chidamide; TKI dasatinib

Eligibility 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.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nanfang Hospital, Southern Medical University

OTHER

Sponsor Role: lead

Responsible Party

Hongsheng Zhou. M.D., Ph.D

M.D., Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Hematology, Nanfang Hospital

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Hongshengq Zhou, MD, Ph.D

Role: CONTACT

zhs1@i.smu.edu.cn

86-20-62787349

Facility Contacts

Hongsheng Zhou, PhD, MD

Role: primary

zhs1@i.smu.edu.cn

86-20-62787349

Other Identifiers

PDT-Ph-Like

Identifier Type: -

Identifier Source: org_study_id