Clinical trial NCT02845882: LBL-2016 for Children or Adolescents in China
Official title: Modified BFM (Berlin-Frankfurt-Munster)Backbone Therapy for Chinese Children or Adolescents With Newly Diagnosed Lymphoblastic Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Lymphoblastic Lymphoma
Lead sponsor: Children's Cancer Group, China
Sponsor class: NETWORK
Collaborators: name: Shanghai Children's Medical Center
name: Tongji Hospital
name: West China Second University Hospital
name: Qilu Hospital of Shandong University
name: Tianjin Medical University Cancer Institute and Hospital
name: Children's Hospital of Soochow University
name: Nanjing Children's Hospital
name: Xiangya Hospital of Central South University
First posted: 2016-07-27
Enrollment: 150
Sex: ALL
Minimum age (years): 12
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

High risk group:patients (failure to qualify a PR, or \>5% BM blasts, or with CNS disease on d33 of induction) receive induction protocol I followed by 6 intensive polychemotherapy blocks (R'), reintensification protocol II, and maintenance for up to a total therapy duration of 104 weeks. Totally, 11 doses of PEG-asparaginase are applied in this group.

Second look biopsy/resection is indicated for patients without CR on day 64 of induction. Allo- or auto-hematopoietic stem-cell transplantation is recommended for patients with residual tumor. Patients who have disease progression at any time will be removed from this protocol therapy.

Eligibility criteria: 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

Primary outcomes:
measure: Event free survival for the whole cohort
timeFrame: 3 years
measure: Event free survival for patients in High risk group
timeFrame: 3 years
Secondary outcomes:
measure: Overall survival for all patients
timeFrame: 5 year
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Second University Hospital
city: Shanghai
country: China
facility: Shanghai Children's Medical Center
Study officials:
affiliation: Shanghai Children's Medical Center
name: Yi-Jin Gao, M.D.
role: PRINCIPAL_INVESTIGATOR
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