Modified BFM-95 Regimen as First-Line Chemotherapy in Adults With T- Lymphoblastic Lymphoma

Study Overview
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Brief Summary
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This study evaluates the efficacy and tolerability of treatment for T-lymphoblastic lymphoma (T-LBL) according to modified BFM-95 regimen for acute lymphoblastic leukemia.

Detailed Description
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All patients received a modified BFM regimen which was derived from the NHL-BFM-95. The differences were as follows: (1) during the course of high-dose methotrexate therapy (HD-MTX), citrovorum folinate (CF) was used for rescue at 36 h after the administration of HD-MTX;(2) Pirarubicin was used instead of daunorubicin (3) Pegaspargase was used instead of L-asparaginase for patients.All patients received induction phase 1 and phase2, followed by the protocol M, reinduction phase 1 and phase2, and maintenance (mercaptopurine 50 mg/m2 daily and methotrexate [MTX] 20 mg/m2 weekly, both orally) for up to a total therapy duration of 24 months. CNS-positive patients received two additional doses of intrathecal MTX at days 18 and 27 of induction and received CRT after reinduction therapy. The dose was 18 Gy.Patients with identifiable blasts in CSF-cytospin preparation but less than 5cells/uL in CSF were not considered CNS positive but received two additional doses of intrathecal MTX at days 18 and 27. For men with testicular involvement,orchiectomy was not performed, and irradiation (20 Gy) of testes was to be confined to biopsy-proven persistent infiltration of testis after protocol M.Response to treatment was evaluated on day 33 and at the end of induction in Modifed BFM-95.Sufficient response was defined as at least 70% tumor regression, less than 5% BM blasts, and no CNS disease on day 33 and complete remission detected by PET / CT at the end of induction.For patients with insufficient response at day 33 or at the end of induction treatment was to be intensified according to the high-risk branch of trial ALL-BFM95, with local radiotherapy (30 Gy) and allogeneic blood stem-cell transplantation.

Official Title
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Modified BFM-95 Regimen for the Treatment of Newly Diagnosed T-lymphoblastic Lymphoma in Adults:a Prospective Phase II Study

Conditions
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Lymphoma, Lymphoblastic

Intervention / Treatment
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* Drug: induction phase1
* Drug: induction phase2
* Drug: protocol M
* Drug: maintenance therapy
* Drug: reinduction phase1
* Drug: reinduction phase2
* Drug: Intrathecal (IT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly diagnosedT-LBL age:18-65years Ann Arbor stage IEto stage IVE at lease one measurable lesion receive no chemotherapy or radiotherapy before Adequate renal function (eg, serum creatinine≤1.5 mg/dL and creatinine clearance ≥50 mL minute), and hepatic function (e.g, total bilirubin≤ 2 times the upper limit of normal and aspartate and alanine transaminase levels ≤ 3 times the upper limit of normal) Exclusion Criteria: mismatch the inclusion criteria systematic central nervous system involvement, previous or concomitant malignancies and any coexisting medical problems that could cause poor compliance with the study protocol.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Modifed BFM-95<br>All patients received induction phase 1 and phase2, followed by the protocol M, reinduction phase 1 and phase2, and maintenance (mercaptopurine 50 mg/m2 daily and methotrexate [MTX] 20 mg/m2 weekly, both orally) for up to a total therapy duration of 24 months. Response to treatment was evaluated on day 33 and at the end of induction in Modifed BFM-95.Sufficient response was defined as at least 70% tumor regression, less than 5% BM blasts, and no CNS disease on day 33 and complete remission detected by PET / CT at the end of induction.For patients with insufficient response at day 33 or at the end of induction treatment was to be intensified according to the high-risk branch of trial ALL-BFM95, with local radiotherapy (30 Gy) and allogeneic blood stem-cell transplantation. | Drug: induction phase1<br>* Vincristine: 1.5 mg/m2 (max 2 mg) iv on days1, 8, 15, 22,Pirarubicin: 30 mg/m2 iv on days1, 8, 15, 22,Prednisone: 60 mg/m2 po on days 1-28. Pegaspargase :3750U/m2 im on days 8,22<br>* Other names: Vincristine,Pirarubicin,Prednisone,Pegaspargase;Drug: induction phase2<br>* Cyclophosphamide: 1000 mg/m2 iv on days 35, 59,Cytarabine: 75 mg/m2 iv on days 35-38, 42-45, 49-52, 56-59,Mercaptopurine: 60 mg/m2 po on days 35-59<br>* Other names: Cyclophosphamide,Cytarabine,Mercaptopurine;Drug: protocol M<br>* Methotrexate: 5 g/m2 d 8, 22, 36, 50;Mercaptopurine:25 mg/m2 1-56<br>* Other names: Methotrexate,Mercaptopurine;Drug: maintenance therapy<br>* 6-mercaptopurine , 50 mg/m 2 daily, and Methotrexate, 20 mg/m 2 once a week.The treatment lasted 2.0 years.Note that there were four additional doses of HD-MTX(5 g/m2 ) every 3 months during the maintenance phase<br>* Other names: 6-mercaptopurine,Methotrexate;Drug: reinduction phase1<br>* Vincristine: 1.5 mg/m2 (max 2 mg) iv on days1, 8, 15, 22,Pirarubicin: 30 mg/m2 iv on days1, 8, 15, 22,Prednisone: 60 mg/m2 po on days 1-28. Pegaspargase :3750U/m2 im on days 8<br>* Other names: Vincristine,Pirarubicin,Prednisone,Pegaspargase;Drug: reinduction phase2<br>* Cyclophosphamide: 1000 mg/m2 iv on days 29,Cytarabine: 75 mg/m2 iv on days 31-34, 38-41,Mercaptopurine: 60 mg/m2 po on days 29-42<br>* Other names: Cyclophosphamide,Cytarabine,Mercaptopurine;Drug: Intrathecal (IT)<br>* methotrexate (15 mg/m 2 ), cytarabine (40 mg/m 2 ) and dexamethasone (4 mg).induction :d1, 15, 29, 45 ;Protocol M:d1, 15, 29, 43;Reinduction:d31,38<br>* Other names: methotrexate ,cytarabine and dexamethasone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival |  | up to end of follow-up-phase (approximately 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete remission rate |  | every 4 weeks,up to completion of induction treatment(approximately 2months) | 
| overall survival |  | up to end of follow-up-phase (approximately 3 years) | 
| safety, including hematological safety and non-hematological safety.All the adverse events will be classified according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) |  | up to end of follow-up-phase (approximately 3 years) |