NHL16: Study For Newly Diagnosed Patients With Acute Lymphoblastic Lymphoma
- Conditions
- Lymphoblastic Lymphoma
- Interventions
- Registration Number
- NCT01451515
- Lead Sponsor
- St. Jude Children's Research Hospital
- Brief Summary
This is a phase II clinical trial using risk-adapted therapy. The treatment is acute lymphoblastic leukemia (ALL)-based therapy, using multi-agent regimens comprising of induction, consolidation, and continuation (maintenance) phases delivered over 24-30 months. Participants will be classified into 3 treatment stratums, based on bone marrow/peripheral blood lymphoma cells involvement at diagnosis and day 8 for T-lymphoblastic lymphoma and bone marrow/peripheral blood lymphoma cells involvement at diagnosis for B-lymphoblastic lymphoma.
The Primary Objective of this study is:
To improve the outcome of children with lymphoblastic lymphoma (LL) who have minimal disseminated disease (MDD) equal to or more than 1% at diagnosis by using MDD- and minimal residual disease (MRD)- based risk-adapted therapy.
The Secondary Objectives of this study are:
* To estimate the event-free survival and overall survival of children with lymphoblastic lymphoma who are treated with MDD- or MRD-based risk- directed therapy.
* To evaluate the prognostic value of levels of MDD at diagnosis and MRD on day 8 of remission induction.
- Detailed Description
TREATMENT PLAN
Treatment will consist of 3 main phases: remission induction, consolidation \[only for patients with any central nervous system (CNS) disease and/or testicular involvement\], and continuation.
* Induction (6-7 weeks).
* Consolidation for participants with CNS involvement or those with testicular disease only (10 weeks).
* Reintensification - Participants with residual disease any time after induction therapy may receive 1-2 cycles of re-intensification therapy and may proceed to allogeneic stem cell transplant if suitable donor is available.
* Continuation Therapy (98-120 weeks).
* Intrathecal Chemotherapy (days 1 and 15; if needed also on days 8 and 22)
TREATMENT SCHEME
T lymphoblastic lymphoma: bone marrow/peripheral blood (BM/PB) involvement (MDD/MRD): Diagnosis: less than 1%; Day 8: +/- (Stratum 1)
* Induction
* Single dose of Cyclophosphamide
* Steroid: prednisone
* Continuation: 98 weeks
T lymphoblastic lymphoma: BM/PB involvement (MDD/MRD): Diagnosis: equal to or greater than 1%; Day 8: - (Stratum 2)
* Induction
* Fractionated Cyclophosphamide
* Steroid: prednisone
* Continuation : 98 weeks
T lymphoblastic lymphoma: BM/PB involvement (MDD/MRD): Diagnosis: equal to or greater than 1%; Day 8: + (Stratum 3)
* Induction
* Fractionated Cyclophosphamide
* Steroid: prednisone and dexamethasone
* Continuation: 120 weeks
B lymphoblastic lymphoma: Stage I-III (Stratum 1)
* Induction
* Single dose of Cyclophosphamide
* Steroid: prednisone
* Continuation: 98 weeks
B lymphoblastic lymphoma: Stage IV or testicular (Stratum 2)
* Induction
* Fractionated Cyclophosphamide
* Steroid: prednisone
* Continuation: 98 weeks
Patients with CNS or testicular involvement will receive Consolidation therapy prior to continuation therapy and receive extended maintenance therapy (120 weeks).
Any patient with detectable disease (MRD, bone marrow or biopsy of residual mass) at the end of induction may be considered for reintensification and/or hematopoietic stem cell transplantation (HSCT).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 23
- Diagnosis of newly diagnosed lymphoblastic lymphoma (patients must have <25% tumor cells in bone marrow by morphology)
- Age ≤ 21 years
- Limited prior therapy, including systemic glucocorticoids for 1 week or less, 1 dose of vincristine, emergency radiation therapy to the mediastinum, and 1 dose of IT chemotherapy. Other circumstances must be cleared by PI or co-PI.
- Written, informed consent and assent following guidelines of the Institutional Review Board, National Cancer Institute (NCI), Food and Drug Administration (FDA), and Office of Human Research Protections (OHRP).
- Participants with prior therapy, other than therapy specified in 3 above.
- Participants who are pregnant or lactating.
- Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Erwinia asparaginase Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Treatment Vincristine Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Treatment Prednisone Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Treatment Daunorubicin Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Treatment PEG-asparaginase Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Treatment Doxorubicin Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Treatment Cytarabine Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Treatment Cyclophosphamide Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Treatment Clofarabine Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Treatment Thioguanine Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Treatment Methotrexate Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Treatment Mercaptopurine Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Treatment Dexamethasone Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Treatment Hydrocortisone Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22. Treatment Etoposide Patients will undergo treatment as described in the intervention section. Interventions include: * Remission induction: prednisone, vincristine, daunorubicin, PEG-asparaginase (or Erwinia asparaginase), IT-MHA (Methotrexate, hydrocortisone, and cytarabine), cyclophosphamide, cytarabine, thioguanine * Consolidation: PEG-asparaginase, High-dose methotrexate (HD-MTX), mercaptopurine * Postremission continuation: Dexamethasone, doxorubicin, vincristine, mercaptopurine, PEG-asparaginase, cyclophosphamide, cytarabine, methotrexate * Reintensification: dexamethasone, cytarabine, etoposide, PEG-asparaginase, clofarabine, cyclophosphamide * All patients receive IT-MHA on days 1 and 15. Some patients also receive additional IT-MHA on days 8 and 22.
- Primary Outcome Measures
Name Time Method Probability of Event-free Survival (EFS) Two years post therapy. For EFS, relapse and second malignancies are considered as failures in addition to death in complete remission. The time to EFS will be set to 0 for patients who fail to achieve complete remission. Kaplan-Meier estimates of the OS and EFS curves are computed, along with estimates of standard errors by Peto's method.
Please note the unit of measurement of probabilities are percentages.
- Secondary Outcome Measures
Name Time Method Minimal Disseminated Disease (MDD) At Diagnosis Detectable disease in bone marrow or blood: A binary measure, positive (detectable), negative (non-detectable)
Probability of Overall Survival (OS) Two years post therapy. For OS, only deaths are considered failures for OS. Kaplan-Meier estimates of the OS curves are computed along with estimates of standard errors by Peto's method.
Please note the unit of measurement of probabilities are percentages.Minimal Residual Disease (MRD) Day 8 Detectable disease in bone marrow or blood: A binary measure, positive (detectable), negative (non-detectable)
Trial Locations
- Locations (2)
Rady Children's Hospital San Diego
🇺🇸San Diego, California, United States
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States