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

An Open-Label, One-Arm, Multi-Site Trial of Precision Diagnosis Directing Target Total Therapy for Adult Ph-like Acute Lymphoblastic Leukemia

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.

Study Overview

• Status: Recruiting
• Conditions: Leukemia; Leukemia, B-cell; Leukemia, Acute; Leukemia, Lymphoblastic
• Intervention / Treatment: Drug: Chidamide; Drug: Dasatinib

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
• Enrollment (Anticipated): 120
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Hongshengq Zhou, MD, Ph.D; Phone Number: 86-20-62787349; Email: zhs1@i.smu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Recruiting
      • Department of Hematology, Nanfang Hospital
      • Contact: Hongsheng Zhou, PhD, MD; Phone Number: 86-20-62787349; Email: zhs1@i.smu.edu.cn

Participation Criteria

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;
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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 Names: TKI dasatinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event free survival	EFS of Ph-like ALL group	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Minimum residual disease after induction	MRD after 1 course	3 months
CR after Induction Therapy	CR rate of Ph-like group	3 months
Death in induction		3 months
Adverse events	AE during PDT-Ph-like	3 years
Relapse	Relapse of Ph-like ALL	3 years
Relapse free survival	RFS	3 years
Overall survival	OS	3 years

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 14, 2016
• Primary Completion (ANTICIPATED): August 30, 2023
• Study Completion (ANTICIPATED): August 30, 2023

Study Registration Dates

• First Submitted: June 9, 2018
• First Submitted That Met QC Criteria: June 11, 2018
• First Posted (ACTUAL): June 20, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 1, 2022
• Last Update Submitted That Met QC Criteria: June 28, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Acute Lymphoblastic Leukemia; Tyrosine Kinase Inhibitor; Histone Deacetylase Inhibitor; Ph-like
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, B-Cell; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Dasatinib
• Other Study ID Numbers: PDT-Ph-Like

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