LBL-2016 for Children or Adolescents in China

Children's Cancer Group, China

Status and phase: Active, not recruiting; Phase 3

Conditions: Lymphoblastic Lymphoma

Treatments: Drug: Methotrexate, 6-mercaptopurine; Drug: Dexamethasone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Doxorubicin, 6-mercaptopurine; Drug: Prednisone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine; Drug: Dexamethasone, Cytarabine, Etoposide, Pegylated-asparaginase; Drug: 6-mercaptopurine,Methotrexate; Drug: Dexamethasone, Vindesine, Methotrexate, Ifosfamide, Daunorubicin, Pegylated-asparaginase; Drug: Dexamethasone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Methotrexate

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT02845882

CCCG-LBL-2016

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 estimated patients

Sex: All

Ages: 12 months to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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150 participants in 3 patient groups

Low risk group

Other group

Description:

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.

Treatment:

Drug: 6-mercaptopurine,Methotrexate

Drug: Prednisone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine

Drug: Methotrexate, 6-mercaptopurine

Intermediate risk group

Other group

Description:

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.

Treatment:

Drug: 6-mercaptopurine,Methotrexate

Drug: Prednisone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine

Drug: Dexamethasone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Doxorubicin, 6-mercaptopurine

Drug: Methotrexate, 6-mercaptopurine

High risk group

Other group

Description:

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.

Treatment:

Drug: Dexamethasone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Methotrexate

Drug: Dexamethasone, Vindesine, Methotrexate, Ifosfamide, Daunorubicin, Pegylated-asparaginase

Drug: Dexamethasone, Cytarabine, Etoposide, Pegylated-asparaginase

Drug: Prednisone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Daunorubicin, 6-mercaptopurine

Drug: Dexamethasone,Vincristine, Pegylated-asparaginase, Cytarabine, Cyclophosphamide, Doxorubicin, 6-mercaptopurine

Drug: Methotrexate, 6-mercaptopurine