Clinical trial NCT03564470: Precision Diagnosis Directing HDACi and TKI Target Therapy for Adult Ph-like ALL
Official title: An Open-Label, One-Arm, Multi-Site Trial of Precision Diagnosis Directing Target Total Therapy for Adult Ph-like Acute Lymphoblastic Leukemia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Leukemia
Leukemia, Acute
Leukemia, Lymphoblastic
Leukemia, B-cell
Keywords: Acute Lymphoblastic Leukemia
Ph-like
Tyrosine Kinase Inhibitor
Histone Deacetylase Inhibitor
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2018-06-20
Enrollment: 120
Sex: ALL
Minimum age (years): 14
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Event free survival
timeFrame: 3 years
Secondary outcomes:
measure: Minimum residual disease after induction
timeFrame: 3 months
measure: CR after Induction Therapy
timeFrame: 3 months
measure: Death in induction
timeFrame: 3 months
measure: Adverse events
timeFrame: 3 years
measure: Relapse
timeFrame: 3 years
measure: Relapse free survival
timeFrame: 3 years
measure: Overall survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Hematology, Nanfang Hospital
state: Guangdong
Study officials:
References: