Ignite Creation Date:
2024-05-06 @ 6:30 PM
Last Modification Date:
2024-10-26 @ 2:49 PM
Study NCT ID:
NCT05681260
Status:
RECRUITING
Last Update Posted:
2024-02-12
First Post:
2022-12-27
Brief Title:
Capizzi Escalating Methotrexate Versus High Dose Methotrexate in Children With Newly Diagnosed T-cell Lymphoblastic Lymphoma T-LBL
Sponsor:
Childrens Cancer Group China
Organization:
Childrens Cancer Group China
Study Overview
Official Title:
A Randomized Trial Using a Modified COG ABFM Regimen Backbone to Investigate Capizzi Escalating Methotrexate Versus High Dose Methotrexate in Children With Newly Diagnosed T-cell Lymphoblastic Lymphoma T-LBL
Status:
RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
T-cell lymphoblastic lymphoma T-LBL is the second most common subtype of non-Hodgkin lymphoma NHL in children and adolescents With current treatment event-free survival EFS rates vary between 7585 Two different MTX intensification strategies are used commonly HD-MTX with leucovorin rescue and Capizzi-style MTX without leucovorin rescue plus PEG-ASP C-MTX Although superior outcome of patients with T-ALL receiving C-MTX compared with HD-MTX on the AALL0434 trial the 2 approaches had not been compared directly in patients with T-LBL There remains controversy on PETCT interpretation in children with NHL Large prospective studies in pediatric patients with T-LBL regarding PETCT value for this is scarce Around 1 pediatric patients with T-LBL will not achieve remission at the end of Induction induction failure The optimal treatment for this small subgroup is largely unclear The BFM HR Blocks usually are applied to these patients even though the efficacy is unknown Novel targeted therapies are needed for use Dasatinib is identified as a targeted therapy for T-cell ALL in preclinical drug screening
Detailed Description:
1 T-cell lymphoblastic lymphoma T-LBL which involves 90 of LBL cases is the second most common subtype of non-Hodgkin lymphoma NHL in children and adolescents With current treatment event-free survival EFS rates vary between 7585 Poor probabilities of survival 1015 for patients after relapse leave no room for treatment de-escalation in frontline protocols Limitations in numbers of newly diagnosed patients impeded evaluation potential prognostic markers and validation or conducting clinical studies
2 In the GER-GPOH-NHL-BFM-95 study the prophylactic cranial radiation was omitted and the intensity of induction therapy was decreased slightly There were no significant increases in CNS relapses suggesting cranial radiation may be reserved for patients with CNS disease at diagnosis The 5-year EFS was worse in NHL-BFM-95 82 than in NHL-BFM-90 90 It was proposed that the major difference in EFS between NHL-BFM-90 and NHL-BFM-95 resulted from the increased number of subsequent neoplasms observed in NHL-BFM-95
3 Two different MTX intensification strategies are used commonly HD-MTX with leucovorin rescue and Capizzi-style MTX without leucovorin rescue plus PEG-ASP C-MTX Although superior outcome of patients with T-ALL receiving C-MTX compared with HD-MTX on the AALL0434 trial the 2 approaches had not been compared directly in patients with T-LBL
4 POG 9404 the small cohort n 66 of lymphoma patients who did not receive HD-MTX the 5-year EFS was 88 Of note all of these patients received prophylactic cranial radiation therapy which has been demonstrated not to be required in T-cell lymphoblastic lymphoma T-LBL patients
5 COG-A5971 evaluated 2 strategies for CNS prophylaxis without CNS irradiation 5 Patients were randomly assigned to receive HD-MTX in interim maintenance BFM-95 or intrathecal chemotherapy throughout maintenance CCG-BFM The overall incidence of CNS relapse was 12 and there was no difference between the treatment arms for CNS relapse DFS or OS Minimal disseminated disease MDD 1 by FLOW at diagnosis was shown to be associated with a worse outcome in this trial a BFM backbone containing HD-MTX Measurement of bone marrow MDD at diagnosis with sequential response monitoring through peripheral blood during remission induction to aid treatment stratification was also suggested in an early COG study The prognostic significance of MDD at End-of-Induction EOI or End-of-Consolidation EOC for T-LBL patients with positive MDD at diagnosis is still unclear
6 COG AALL0434 the COG ABFM regimen with C-MTX provided excellent DFS without cranial radiation for patients with standard risk T-LBL 85 Arm A n82 completed 64 and high risk T-LBL 85 Arm A n61 completed 51 although patients with CNS 3 were not included It appears that C-MTX may have negated the prognostic impact of MDD
7 Nelarabine is unavailable in mainland China at this time which did not show benefit in COG AALL0434 study
8 AALL07P1 10 patients with T-LBL in first relapse treated with a 4-drug induction regimen adding bortezomib 7 had a response 1 had a complete response 2 had unconfirmed complete responses and 4 had partial responses
9 COG AALL1231 for T-LBL the 4-year EFS and OS were better in bortezomib group than the control group 864 and 895 vs 765 and 783 p0041 and 0009 respectively Incorporating bortezomib into standard therapy for de novo T-LBL appears beneficial
10 A biopsy for pathological examination of a mediastinal residual mass is a clinical dilemma Currently conventional imaging is still considered as the standard modality for evaluating pediatric patients with NHL at diagnosis and subsequent response There remains controversy on PETCT interpretation in children with NHL Large prospective studies in pediatric patients with T-LBL regarding PETCT value for this is scarce
11 Although an overlap in morphology and immune-phenotyping exists in T-LBL and T-cell acute lymphoblastic leukemia T-ALL different disease distribution suggests possible different genetic profiles and pathogenesis Except for stage none of other parameters is used in the current stratification system outside of clinical trials for T-LBL several candidates but none have been validated sufficiently Little is known about biomarkers with prognostic relevance for T-LBL To improve risk stratification strategy and better understand biologic rationale for incorporating novel therapies chemicals target agents and immunotherapy into a conventional chemotherapy backbone translational research to identify molecular markers with prognostic relevance in T-LBL is highly recommended
12 With the current treatment around 1 pediatric patients with T-LBL will not achieve remission at the end of Induction induction failure The optimal treatment for this small subgroup is largely unclear The BFM HR Blocks usually are applied to these patients even though the efficacy is unknown Novel targeted therapies are needed for use Dasatinib is identified as a targeted therapy for T-cell ALL in preclinical drug screening
2 In the GER-GPOH-NHL-BFM-95 study the prophylactic cranial radiation was omitted and the intensity of induction therapy was decreased slightly There were no significant increases in CNS relapses suggesting cranial radiation may be reserved for patients with CNS disease at diagnosis The 5-year EFS was worse in NHL-BFM-95 82 than in NHL-BFM-90 90 It was proposed that the major difference in EFS between NHL-BFM-90 and NHL-BFM-95 resulted from the increased number of subsequent neoplasms observed in NHL-BFM-95
3 Two different MTX intensification strategies are used commonly HD-MTX with leucovorin rescue and Capizzi-style MTX without leucovorin rescue plus PEG-ASP C-MTX Although superior outcome of patients with T-ALL receiving C-MTX compared with HD-MTX on the AALL0434 trial the 2 approaches had not been compared directly in patients with T-LBL
4 POG 9404 the small cohort n 66 of lymphoma patients who did not receive HD-MTX the 5-year EFS was 88 Of note all of these patients received prophylactic cranial radiation therapy which has been demonstrated not to be required in T-cell lymphoblastic lymphoma T-LBL patients
5 COG-A5971 evaluated 2 strategies for CNS prophylaxis without CNS irradiation 5 Patients were randomly assigned to receive HD-MTX in interim maintenance BFM-95 or intrathecal chemotherapy throughout maintenance CCG-BFM The overall incidence of CNS relapse was 12 and there was no difference between the treatment arms for CNS relapse DFS or OS Minimal disseminated disease MDD 1 by FLOW at diagnosis was shown to be associated with a worse outcome in this trial a BFM backbone containing HD-MTX Measurement of bone marrow MDD at diagnosis with sequential response monitoring through peripheral blood during remission induction to aid treatment stratification was also suggested in an early COG study The prognostic significance of MDD at End-of-Induction EOI or End-of-Consolidation EOC for T-LBL patients with positive MDD at diagnosis is still unclear
6 COG AALL0434 the COG ABFM regimen with C-MTX provided excellent DFS without cranial radiation for patients with standard risk T-LBL 85 Arm A n82 completed 64 and high risk T-LBL 85 Arm A n61 completed 51 although patients with CNS 3 were not included It appears that C-MTX may have negated the prognostic impact of MDD
7 Nelarabine is unavailable in mainland China at this time which did not show benefit in COG AALL0434 study
8 AALL07P1 10 patients with T-LBL in first relapse treated with a 4-drug induction regimen adding bortezomib 7 had a response 1 had a complete response 2 had unconfirmed complete responses and 4 had partial responses
9 COG AALL1231 for T-LBL the 4-year EFS and OS were better in bortezomib group than the control group 864 and 895 vs 765 and 783 p0041 and 0009 respectively Incorporating bortezomib into standard therapy for de novo T-LBL appears beneficial
10 A biopsy for pathological examination of a mediastinal residual mass is a clinical dilemma Currently conventional imaging is still considered as the standard modality for evaluating pediatric patients with NHL at diagnosis and subsequent response There remains controversy on PETCT interpretation in children with NHL Large prospective studies in pediatric patients with T-LBL regarding PETCT value for this is scarce
11 Although an overlap in morphology and immune-phenotyping exists in T-LBL and T-cell acute lymphoblastic leukemia T-ALL different disease distribution suggests possible different genetic profiles and pathogenesis Except for stage none of other parameters is used in the current stratification system outside of clinical trials for T-LBL several candidates but none have been validated sufficiently Little is known about biomarkers with prognostic relevance for T-LBL To improve risk stratification strategy and better understand biologic rationale for incorporating novel therapies chemicals target agents and immunotherapy into a conventional chemotherapy backbone translational research to identify molecular markers with prognostic relevance in T-LBL is highly recommended
12 With the current treatment around 1 pediatric patients with T-LBL will not achieve remission at the end of Induction induction failure The optimal treatment for this small subgroup is largely unclear The BFM HR Blocks usually are applied to these patients even though the efficacy is unknown Novel targeted therapies are needed for use Dasatinib is identified as a targeted therapy for T-cell ALL in preclinical drug screening
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None