Modified BFM (Berlin-Frankfurt-Munster)Backbone Therapy for Chinese Children or Adolescents With Newly Diagnosed Lymphoblastic Lymphoma
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 150
- Locations
- 2
- Primary Endpoint
- Event free survival for patients in High risk group
Study Overview
Brief Summary
The outcomes of children with lymphoblastic lymphoma (LBL) in China in the investigators' previous study were not unexpected. In this study, through further modification treatment protocols and strengthen domestic multicenter collaboration, the investigators try to improve survival for children with LBL when compared to the previous study.
Detailed Description
The treatment for LBL is an ALL (acute lymphoblastic leukemia)-based treatment. Additional, high dose L-asparaginase was reported to improve disease-free survival for patients with ALL. The event free survival (EFS) for pediatric LBL in most western countries have achieved 75% to 85%. However, the outcomes of children with LBL in China were not unexpected. In the previous study (CCCG-LBL-2010, 2009-2013), 96 patients with newly diagnosed LBL from 7 Chinese pediatric oncology centers were included. At a median follow-up of 21 months (range, 0.3~60.7months), the 2-year event free survival was 68±5% in all patients. Patients who had achieved complete remission on day 33 of induction had significantly better EFS than those who had not (77±6% v.s.17±10%, p<0.005). In the current trial, the investigators try to improve survival for children with LBL in China through further modification treatment protocols and strengthen domestic multicenter collaboration.
The BFM backbone will be used as the standard backbone therapy for this study. Three doses of daunorubicin are prescribed in induction compared with 4 doses in BFM studies. Cranial radiotherapy only saved for patients (>2 yrs) with CNS disease at presentation.
Complete remission (CR) is defined as at least 75% tumor regression, less than 5% BM (bone marrow)blasts, no CNS (central nervous system) disease, and disappearances of all evidence of disease from all sites for at least 4 weeks. Partial response (PR) is defined as > 50% tumor regression, and no new lesions.Response to treatment is evaluated on day 33 and day 64 of induction.Patients will be stratified into 3 risk groups.
Low risk group: patients (stage I or II) receive induction protocol I followed by the extracompartmental protocol M, and maintenance for up to a total therapy duration of 96 weeks. Totally, 3 doses of PEG-asparaginase (Pegylated-asparaginase) are applied in this group.
Intermediate risk group: patients (stage III or IV or receiving steroids within one week prior to the diagnosis) receive induction protocol I followed by the extracompartmental protocol M, reintensification protocol II, and maintenance for up to a total therapy duration of 104 weeks.Totally, 5 doses of PEG-asparaginase are applied in this group.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 12 Months to 18 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients must have newly diagnosed lymphoblastic lymphoma; Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids (<420mg/m2)
Exclusion Criteria
- •Patients with Down syndrome;
- •Morphologically unclassifiable lymphoma
- •Patients with congenital immunodeficiency, chromosomal breakage syndrome, prior organ transplantation, previous malignancy of any type, or known positive HIV serology.
- •Evidence of pregnancy or lactation period.
- •Ph+ lymphoblastic lymphoma
Arms & Interventions
Low risk group
Stage I or II: Induction I followed by extracompartmental Protocol M, and maintenance therapy for up to a total therapy duration of 96 weeks. Twenty triple intrathecal injections.
Intervention: 6-mercaptopurine,Methotrexate (Drug)
Low risk group
Stage I or II: Induction I followed by extracompartmental Protocol M, and maintenance therapy for up to a total therapy duration of 96 weeks. Twenty triple intrathecal injections.
Intervention: Methotrexate, 6-mercaptopurine (Drug)
Intermediate risk group
Stage III or IV or receiving steroids within one week prior to the diagnosis: Induction protocol I followed by the extracompartmental protocol M, reintensification protocol II, and maintenance therapy for up to a total therapy duration of 104 weeks. Twenty-two triple intrathecal injections.
Intervention: 6-mercaptopurine,Methotrexate (Drug)
High risk group
Failure to qualify a PR, or >5% BM blasts, or with CNS disease on d33 of induction: Induction protocol I followed by 6 intensive polychemotherapy blocks (HR1'-HR2'-HR3'-HR1'-HR2'-HR3'), reintensification protocol II, and maintenance therapy for up to a total therapy duration of 104 weeks. Twenty-two triple intrathecal injections.
Intervention: Dexamethasone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Methotrexate (Drug)
High risk group
Failure to qualify a PR, or >5% BM blasts, or with CNS disease on d33 of induction: Induction protocol I followed by 6 intensive polychemotherapy blocks (HR1'-HR2'-HR3'-HR1'-HR2'-HR3'), reintensification protocol II, and maintenance therapy for up to a total therapy duration of 104 weeks. Twenty-two triple intrathecal injections.
Intervention: Dexamethasone, Vindesine, Methotrexate, Ifosfamide, Daunorubicin, Pegylated-asparaginase (Drug)
High risk group
Failure to qualify a PR, or >5% BM blasts, or with CNS disease on d33 of induction: Induction protocol I followed by 6 intensive polychemotherapy blocks (HR1'-HR2'-HR3'-HR1'-HR2'-HR3'), reintensification protocol II, and maintenance therapy for up to a total therapy duration of 104 weeks. Twenty-two triple intrathecal injections.
Intervention: Dexamethasone, Cytarabine, Etoposide, Pegylated-asparaginase (Drug)
Low risk group
Stage I or II: Induction I followed by extracompartmental Protocol M, and maintenance therapy for up to a total therapy duration of 96 weeks. Twenty triple intrathecal injections.
Intervention: Prednisone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine (Drug)
Intermediate risk group
Stage III or IV or receiving steroids within one week prior to the diagnosis: Induction protocol I followed by the extracompartmental protocol M, reintensification protocol II, and maintenance therapy for up to a total therapy duration of 104 weeks. Twenty-two triple intrathecal injections.
Intervention: Methotrexate, 6-mercaptopurine (Drug)
Intermediate risk group
Stage III or IV or receiving steroids within one week prior to the diagnosis: Induction protocol I followed by the extracompartmental protocol M, reintensification protocol II, and maintenance therapy for up to a total therapy duration of 104 weeks. Twenty-two triple intrathecal injections.
Intervention: Dexamethasone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Doxorubicin, 6-mercaptopurine (Drug)
Intermediate risk group
Stage III or IV or receiving steroids within one week prior to the diagnosis: Induction protocol I followed by the extracompartmental protocol M, reintensification protocol II, and maintenance therapy for up to a total therapy duration of 104 weeks. Twenty-two triple intrathecal injections.
Intervention: Prednisone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine (Drug)
High risk group
Failure to qualify a PR, or >5% BM blasts, or with CNS disease on d33 of induction: Induction protocol I followed by 6 intensive polychemotherapy blocks (HR1'-HR2'-HR3'-HR1'-HR2'-HR3'), reintensification protocol II, and maintenance therapy for up to a total therapy duration of 104 weeks. Twenty-two triple intrathecal injections.
Intervention: Prednisone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine (Drug)
High risk group
Failure to qualify a PR, or >5% BM blasts, or with CNS disease on d33 of induction: Induction protocol I followed by 6 intensive polychemotherapy blocks (HR1'-HR2'-HR3'-HR1'-HR2'-HR3'), reintensification protocol II, and maintenance therapy for up to a total therapy duration of 104 weeks. Twenty-two triple intrathecal injections.
Intervention: Dexamethasone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Doxorubicin, 6-mercaptopurine (Drug)
High risk group
Failure to qualify a PR, or >5% BM blasts, or with CNS disease on d33 of induction: Induction protocol I followed by 6 intensive polychemotherapy blocks (HR1'-HR2'-HR3'-HR1'-HR2'-HR3'), reintensification protocol II, and maintenance therapy for up to a total therapy duration of 104 weeks. Twenty-two triple intrathecal injections.
Intervention: Methotrexate, 6-mercaptopurine (Drug)
Outcomes
Primary Outcomes
Event free survival for patients in High risk group
Time Frame: 3 years
Event free survival for the whole cohort
Time Frame: 3 years
Secondary Outcomes
- Overall survival for all patients(5 year)