Precision Diagnosis Directing HDACi and TKI Target Therapy for Adult Ph-like ALL
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|ClinicalTrials.gov Identifier: NCT03564470|
Recruitment Status : Recruiting
First Posted : June 20, 2018
Last Update Posted : June 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Leukemia, Acute Leukemia, Lymphoblastic Leukemia, B-cell||Drug: Chidamide Drug: Dasatinib||Phase 2 Phase 3|
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;
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|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
Chidamide will be added to chidamide arm Ph-like ALL(CRLF2 high-expression, CRLF2/EPO/JAK2 rearrangement, JAK/IL-7R/SH2B3 mutation, etc).
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
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).
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
- Event free survival [ Time Frame: 3 years ]EFS of Ph-like ALL group
- Minimum residual disease after induction [ Time Frame: 3 months ]MRD after 1 course
- CR after Induction Therapy [ Time Frame: 3 months ]CR rate of Ph-like group
- Death in induction [ Time Frame: 3 months ]
- Adverse events [ Time Frame: 3 years ]AE during PDT-Ph-like
- Relapse [ Time Frame: 3 years ]Relapse of Ph-like ALL
- Relapse free survival [ Time Frame: 3 years ]RFS
- Overall survival [ Time Frame: 3 years ]OS
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
|Contact: Hongshengq Zhou, MD, Ph.Dfirstname.lastname@example.org|
|Department of Hematology, Nanfang Hospital||Recruiting|
|Guangzhou, Guangdong, China, 510515|
|Contact: Hongsheng Zhou, PhD, MD 86-20-62787349 email@example.com|