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Precision Diagnosis Directing HDACi Chidamide Target Therapy for Adult T-LBL/ALL
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Leukemia Leukemia, Acute Adult Lymphoblastic Lymphoma Leukemia, Lymphoblastic Leukemia, T Cell Adult Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Lymphoblastic Leukemia | Drug: Dexamethasone Drug: vincristine Drug: Cyclophosphamide Drug: Idarubicin Drug: Pegaspargase Drug: Adriamycin Drug: Methotrexate Drug: 6-mercaptopurine. Drug: Etoposide Drug: Cytarabine Procedure: Bone marrow aspiration Procedure: Intrathecal injection Radiation: Radiation therapy Genetic: NGS Procedure: allogeneic hematopoietic stem cell transplantation Diagnostic Test: Flow-MRD Diagnostic Test: FISH Diagnostic Test: Flow immunophenotyping Diagnostic Test: Karyotyping Drug: Chidamide Diagnostic Test: PET-CT scan | Phase 2 Phase 3 |
T-lymphoblastic lymphoma/leukemia is a neoplasm of lymphoblasts committed to the T-cell lineage, typically composed of small to medium-sized blast with scant cytoplasm, moderately condensed to dispersed chromatin, and inconspicuous nucleoli, involving bone marrow and blood or presenting with primary involvement of the thymus or of nodal or extranodal sites. T-ALL/LBL is generally considered a higher-risk disease than B-ALL. Compared to B-ALL, T-LBL/ALL is associated with a higher risk of induction failure, early relapse, and isolated CNS relapse.
Chidamide is a novel oral HDACi with promising activity in non-Hodgkin lymphoma (NHL). Chidamide, a new oral isotype-selective HDACi, approved in China for the treatment of R/R PTCL in December 2014. 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-ALL-LBL is aimed to evaluate the safety and effect of oral histone deacetylase inhibitor chidamide for adult T-ALL/LBL. Compared to PDT-ALL-2016 for B-ALL, HDACi chidamide will be administrated from induction therapy to maintenance therapy, along with higher dose of consolidation regimen of cytarabine, methotrexate, cyclophosphamide.
The intervention of PDT-ALL-LBL consists of diagnostic test (bone marrow aspiration, flow immunophenotyping, karyotyping，FISH, NGS, Flow-MRD), induction regimen (chidamide, dexamethasone, vincristine, cyclophosphamide, Idarubicin, pegaspargase), consolidation regimen (chidamide, prednisone, cytarabine, methotrexate, cyclophosphamide, etoposide, adriamycin, 6-mercaptopurine, pegaspargase), MRD assessment (MRD1/d14, MRD2/d24, MRD3/d45, MRD4/pre-allo-HSCT) and maintenance regimen (chidamide, vincristine, methotrexate, 6-mercaptopurine), intrathecal injection, radiation therapy (for mediastinum- and/or central nervous system-involved lymphoma/leukemia) and allogeneic hematopoietic stem cell transplantation for patients with donor.
Induction Regimen-Pretreatment: dexamethasone, -3d to 0d; Induction regimen VICLD: VCR: d1, d8, d15, d22; IDA: d1, d8; CTX: 1g/m2, 1; PEG-asp: 2000-2500IU/m2, 1, 15; dexamethasone: 1-24; chidamide: 10mg/d, po, qd. Flow-based MRD assessment: d14, d24 during induction regimen, d45, and pre-HSCT. Salvage regimen VLCAM (MRD1/d24>1%): CTX, d25; AraC 50mg/m2, d25-31; 6-MP: 25-31, PEG-asp: 2500IU/m2, d26. Consolidation Module (CM)-CM1: AraC 3g/m2, q12h, d1-2, Dex: 10mg/m2, d1-2, PEG-asp: 2, 6-MP: d1-7, chidamide, po qd; CM2: MTX 5g/m2, 1, Dex: 10mg/m2, 1-2, PEG-asp: d2, 6-MP: 1-7, chidamide, po qd; CM3: CTX 1g/m2, 1-3, PEG-asp: 2, 6-MP: 1-7, chidamide, po qd. CM4-6: repeat CM 1-3. Re-Induction: VICLD after CM6. CM7-9: repeat CM1-3. Allo-HSCT: after CM3 when matched-related-donor (MRD), haploidentical related donor (HRD) or matched-unrelated-donor (MUD) available. Non-allo-HSCT: finish CM4-9 and CPOMP maintenance. Maintenance Module-CPOMP: chidamide, po qd for 24 months; Pred: for 12 months; VCR for 12 months; MTX: for 24m months; 6-MP for 24 months.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 80 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | An Open-Label, One-Arm, Multi-Site Trial of Precision Diagnosis Directing Histone Deacetylase Inhibitor Chidamide Total Therapy for Adult T-lymphoblastic Lymphoma/Leukemia |
| Actual Study Start Date : | February 14, 2016 |
| Estimated Primary Completion Date : | May 30, 2021 |
| Estimated Study Completion Date : | May 30, 2021 |
| Arm | Intervention/treatment |
|---|---|
|
Experimental: PDT-ALL-LBL
The intervention of PDT-ALL-LBL consists of diagnostic test (bone marrow aspiration, flow immunophenotyping, karyotyping，FISH, NGS, Flow-MRD, PET-CT scan), induction regimen (chidamide, dexamethasone, vincristine, cyclophosphamide, idarubicin, pegaspargase), consolidation regimen (chidamide, prednisone, cytarabine, methotrexate, cyclophosphamide, etoposide, adriamycin, 6-mercaptopurine, pegaspargase), MRD assessment and maintenance regimen (chidamide, prednisone, vincristine, methotrexate, 6-mercaptopurine), intrathecal injection chemotherapy (methotrexate, cytarabine, dexamethasone), radiation therapy (for mediastinum- and/or central nervous system-involved lymphoma/leukemia) and allogeneic hematopoietic stem cell transplantation for patients with donor.
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Drug: Dexamethasone
Dexamethasone will be added in Pre-phase Regimen, Induction-Regimen, Consolidation-Module of PDT-ALL-LBL protocol.
Other Name: DXM
Drug: vincristine Vincristine will be added to Induction-Regimen, Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
Other Name: VCR
Drug: Cyclophosphamide CTX will be added to Induction-Regimen, Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
Other Name: CTX
Drug: Idarubicin IDA will be added to Induction-Regimen and Consolidation-Module of PDT-ALL-LBL protocol.
Other Name: IDA
Drug: Pegaspargase PEG-ASP will be added to Induction-Regimen and Consolidation-Module of PDT-ALL-LBL protocol.
Other Name: PEG-ASP
Drug: Adriamycin Adriamycin will be added to Consolidation-Module of PDT-ALL-LBL protocol.
Other Name: ADR
Drug: Methotrexate Methotrexate will be added to Consolidation-Module of PDT-ALL-LBL protocol.
Other Name: MTX
Drug: 6-mercaptopurine. Mercaptopurine will be added to Consolidation-Module and Maintenance-Module of PDT-ALL-LBL protocol.
Other Name: 6-MP
Drug: Etoposide VP-16 will be added to Consolidation-Module of PDT-ALL-LBL protocol.
Other Name: VP-16
Drug: Cytarabine AraC will be added to Consolidation-Module of PDT-ALL-LBL protocol.
Other Name: AraC
Procedure: Bone marrow aspiration Bone marrow aspiration and additional tests will be performed in all module of PDT-ALL-LBL protocol.
Other Name: BM smear
Procedure: Intrathecal injection Intrathecal injection of chemotherapy will be performed in PDT-ALL-LBL protocol.
Other Name: IT
Radiation: Radiation therapy Radiation therapy will be performed for mediastinum and/or central nervous system leukemia/lymphoma in PDT-ALL-LBL protocol.
Other Name: RT
Genetic: NGS Next-Generation-Sequencing (NGS) will be performed in PDT-ALL-LBL protocol.
Procedure: allogeneic hematopoietic stem cell transplantation Allo-HSCT will be added to LBL patients with available donor in PDT-ALL-LBL protocol.
Other Name: Allo-HSCT
Diagnostic Test: Flow-MRD Flow-MRD will be added to PDT-ALL-LBL for bone marrow and cerebrospinal fluid samples.
Diagnostic Test: FISH FISH will be added to PDT-ALL-LBL for bone marrow samples.
Diagnostic Test: Flow immunophenotyping Flow immunophenotyping will be performed in PDT-ALL-LBL protocol.
Diagnostic Test: Karyotyping Karyotyping will be performed in PDT-ALL-LBL protocol.
Drug: Chidamide HDACi chidamide will be added to induction regimen, consolidation and maintenance module of PDT-ALL-LBL.
Other Name: HDACi Chidamide
Diagnostic Test: PET-CT scan PET-scan will be performed for T-LBL patients for MRD assessment in PDT-ALL-LBL.
Other Name: PET-CT
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- Event-Free-Survival [ Time Frame: 3 years ]3 years EFS of LBL/ALL patients enrolled in PDT-ALL-LBL
- Minimum residual disease after induction [ Time Frame: 3 months ]MRD after induction regimen of PDT-ALL-LBL protocol
- CR after Induction Therapy [ Time Frame: 3 months ]CR after induction regimen of PDT-ALL-LBL protocol
- Death in induction [ Time Frame: 3 months ]Dearth during induction regimen of PDT-ALL-LBL
- Adverse events [ Time Frame: 3 years ]AE of 3 years of LBL patients enrolled in PDT-ALL-LBL
- Relapse [ Time Frame: 3 years ]Cumulative incidence relapse rate of 3 years of LBL patients enrolled in PDT-ALL-LBL protocol
- Relapse free survival [ Time Frame: 3 years ]3 years RFS of LBL patients enrolled in PDT-ALL-LBL protocol
- Overall survival [ Time Frame: 3 years ]3 years OS of LBL patients enrolled in PDT-ALL-LBL protocol
| Ages Eligible for Study: | 14 Years to 55 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 14-55 years old;
- LBL/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-ALL-LBL protocol.
| Contact: Hongsheng Zhou | +862062787349 | zhs1@i.smu.edu.cn |
| China, Guangdong | |
| Department of Hematology, Nanfang Hospital | Recruiting |
| Guangzhou, Guangdong, China, 510515 | |
| Contact: Hongsheng Zhou +862062787349 zhs1@i.smu.edu.cn | |
| Study Chair: | Qifa Liu, MD | Department of Hematology Nanfang Hospital |
| Tracking Information | |||||||
|---|---|---|---|---|---|---|---|
| First Submitted Date ICMJE | June 11, 2018 | ||||||
| First Posted Date ICMJE | June 21, 2018 | ||||||
| Last Update Posted Date | June 21, 2018 | ||||||
| Actual Study Start Date ICMJE | February 14, 2016 | ||||||
| Estimated Primary Completion Date | May 30, 2021 (Final data collection date for primary outcome measure) | ||||||
| Current Primary Outcome Measures ICMJE |
Event-Free-Survival [ Time Frame: 3 years ] 3 years EFS of LBL/ALL patients enrolled in PDT-ALL-LBL
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| Original Primary Outcome Measures ICMJE | Same as current | ||||||
| Change History | No Changes Posted | ||||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE | Same as current | ||||||
| Current Other Pre-specified Outcome Measures | Not Provided | ||||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||||
| Descriptive Information | |||||||
| Brief Title ICMJE | Precision Diagnosis Directing HDACi Chidamide Target Therapy for Adult T-LBL/ALL | ||||||
| Official Title ICMJE | An Open-Label, One-Arm, Multi-Site Trial of Precision Diagnosis Directing Histone Deacetylase Inhibitor Chidamide Total Therapy for Adult T-lymphoblastic Lymphoma/Leukemia | ||||||
| Brief Summary | Based on the pediatric-inspired, PEG-L-asparaginase-intensified and MRD-directed PDT-ALL-2016 protocol, this open-label, one-arm, multi-site trial PDT-ALL-LBL is aimed to evaluate the safety and effect of oral histone deacetylase inhibitor chidamide for adult T-ALL/LBL. Compared to PDT-ALL-2016 for B-ALL, HDACi chidamide will be administrated from induction therapy to maintenance therapy, along with higher dose of consolidation regimen of cytarabine, methotrexate, cyclophosphamide. | ||||||
| Detailed Description |
T-lymphoblastic lymphoma/leukemia is a neoplasm of lymphoblasts committed to the T-cell lineage, typically composed of small to medium-sized blast with scant cytoplasm, moderately condensed to dispersed chromatin, and inconspicuous nucleoli, involving bone marrow and blood or presenting with primary involvement of the thymus or of nodal or extranodal sites. T-ALL/LBL is generally considered a higher-risk disease than B-ALL. Compared to B-ALL, T-LBL/ALL is associated with a higher risk of induction failure, early relapse, and isolated CNS relapse. Chidamide is a novel oral HDACi with promising activity in non-Hodgkin lymphoma (NHL). Chidamide, a new oral isotype-selective HDACi, approved in China for the treatment of R/R PTCL in December 2014. 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-ALL-LBL is aimed to evaluate the safety and effect of oral histone deacetylase inhibitor chidamide for adult T-ALL/LBL. Compared to PDT-ALL-2016 for B-ALL, HDACi chidamide will be administrated from induction therapy to maintenance therapy, along with higher dose of consolidation regimen of cytarabine, methotrexate, cyclophosphamide. The intervention of PDT-ALL-LBL consists of diagnostic test (bone marrow aspiration, flow immunophenotyping, karyotyping，FISH, NGS, Flow-MRD), induction regimen (chidamide, dexamethasone, vincristine, cyclophosphamide, Idarubicin, pegaspargase), consolidation regimen (chidamide, prednisone, cytarabine, methotrexate, cyclophosphamide, etoposide, adriamycin, 6-mercaptopurine, pegaspargase), MRD assessment (MRD1/d14, MRD2/d24, MRD3/d45, MRD4/pre-allo-HSCT) and maintenance regimen (chidamide, vincristine, methotrexate, 6-mercaptopurine), intrathecal injection, radiation therapy (for mediastinum- and/or central nervous system-involved lymphoma/leukemia) and allogeneic hematopoietic stem cell transplantation for patients with donor. Induction Regimen-Pretreatment: dexamethasone, -3d to 0d; Induction regimen VICLD: VCR: d1, d8, d15, d22; IDA: d1, d8; CTX: 1g/m2, 1; PEG-asp: 2000-2500IU/m2, 1, 15; dexamethasone: 1-24; chidamide: 10mg/d, po, qd. Flow-based MRD assessment: d14, d24 during induction regimen, d45, and pre-HSCT. Salvage regimen VLCAM (MRD1/d24>1%): CTX, d25; AraC 50mg/m2, d25-31; 6-MP: 25-31, PEG-asp: 2500IU/m2, d26. Consolidation Module (CM)-CM1: AraC 3g/m2, q12h, d1-2, Dex: 10mg/m2, d1-2, PEG-asp: 2, 6-MP: d1-7, chidamide, po qd; CM2: MTX 5g/m2, 1, Dex: 10mg/m2, 1-2, PEG-asp: d2, 6-MP: 1-7, chidamide, po qd; CM3: CTX 1g/m2, 1-3, PEG-asp: 2, 6-MP: 1-7, chidamide, po qd. CM4-6: repeat CM 1-3. Re-Induction: VICLD after CM6. CM7-9: repeat CM1-3. Allo-HSCT: after CM3 when matched-related-donor (MRD), haploidentical related donor (HRD) or matched-unrelated-donor (MUD) available. Non-allo-HSCT: finish CM4-9 and CPOMP maintenance. Maintenance Module-CPOMP: chidamide, po qd for 24 months; Pred: for 12 months; VCR for 12 months; MTX: for 24m months; 6-MP for 24 months. |
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| Study Type ICMJE | Interventional | ||||||
| Study Phase ICMJE | Phase 2 Phase 3 |
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| Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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| Condition ICMJE |
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| Intervention ICMJE |
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| Study Arms ICMJE | Experimental: PDT-ALL-LBL
The intervention of PDT-ALL-LBL consists of diagnostic test (bone marrow aspiration, flow immunophenotyping, karyotyping，FISH, NGS, Flow-MRD, PET-CT scan), induction regimen (chidamide, dexamethasone, vincristine, cyclophosphamide, idarubicin, pegaspargase), consolidation regimen (chidamide, prednisone, cytarabine, methotrexate, cyclophosphamide, etoposide, adriamycin, 6-mercaptopurine, pegaspargase), MRD assessment and maintenance regimen (chidamide, prednisone, vincristine, methotrexate, 6-mercaptopurine), intrathecal injection chemotherapy (methotrexate, cytarabine, dexamethasone), radiation therapy (for mediastinum- and/or central nervous system-involved lymphoma/leukemia) and allogeneic hematopoietic stem cell transplantation for patients with donor.
Interventions:
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| Publications * | Not Provided | ||||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||||
| Recruitment Status ICMJE | Unknown status | ||||||
| Estimated Enrollment ICMJE |
80 | ||||||
| Original Estimated Enrollment ICMJE | Same as current | ||||||
| Estimated Study Completion Date ICMJE | May 30, 2021 | ||||||
| Estimated Primary Completion Date | May 30, 2021 (Final data collection date for primary outcome measure) | ||||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 14 Years to 55 Years (Child, Adult) | ||||||
| Accepts Healthy Volunteers ICMJE | No | ||||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||||
| Listed Location Countries ICMJE | China | ||||||
| Removed Location Countries | |||||||
| Administrative Information | |||||||
| NCT Number ICMJE | NCT03564704 | ||||||
| Other Study ID Numbers ICMJE | PDT-ALL-LBL | ||||||
| Has Data Monitoring Committee | Yes | ||||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE | Not Provided | ||||||
| Responsible Party | Qifa Liu, Nanfang Hospital of Southern Medical University | ||||||
| Study Sponsor ICMJE | Nanfang Hospital of Southern Medical University | ||||||
| Collaborators ICMJE | Not Provided | ||||||
| Investigators ICMJE |
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| PRS Account | Nanfang Hospital of Southern Medical University | ||||||
| Verification Date | June 2018 | ||||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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