precision diagnosis directing hdaci chidamide target therapy for adult etp-all

Conditions: Leukemia, Acute; Leukemia, T Cell; Leukemia, Lymphoblastic

Summary: 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.

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.

Eligibility criteria:
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.

Keywords: early t-cell precursor acute lymphoblastic leukemia histone deacetylase inhibitor chidamide