Modified MRCUKALLⅫ/ECOGE2993 Regimen for ALL

Study Overview
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Brief Summary
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This prospective study was conducted to evaluate the efficacy and safety profiles of Modified MRCUKALLⅫ/ECOGE2993 Regimen in young adults with newly diagnosed, low-risk, Philadelphia chromosome negative acute lymphoblastic leukaemia.

Detailed Description
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All patients received a modified BFM regimen which was derived from the MRCUKALLⅫ/ECOGE2993 Regimen.The differences were as follows:(1) cranial prophylactic radiotherapy was omitted (2) Pegaspargase was used instead of L- asparaginase for patient.(3)Two additional Pegaspargase treatments were added into consolidation therapy.

Official Title
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A Prospective Phase II Trial of Modified MRC UKALL Ⅻ/ECOG E2993 Regimen in the Treatment of Low Risk Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia for Young Adults

Conditions
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Leukaemia,Lymphoblastic

Intervention / Treatment
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* Drug: Vincristine
* Drug: Daunorubicin
* Drug: Pegaspargase
* Drug: Prednisone
* Drug: Intrathecal Methotrexate
* Drug: Cyclophosphamide
* Drug: Cytarabine
* Drug: 6-Mercaptopurine
* Drug: Methotrexate
* Drug: Etoposide
* Drug: dexamethasone
* Drug: thioguanine
* Drug: intrathecal cytarabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: newly diagnosed ALL age:18-35years WBC count below 30×109/L(B lineage)；WBC count below 100×109/L(T lineage) absence of t(9;22), t(1;19), t(4;11) or any other 11q23 rearrangements 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: 35 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: Modified MRCUKALLⅫ/ECOGE2993 Regimen<br>All patients received phase 1 of induction therapy, which consisted of daunorubicin,vincristine,Pegaspargase,prednisone and methotrexate (intrathecally).Patients went on to phase 2 at the end of phase 1.Phase 2 therapy consisted of cyclophosphamide,cytarabine,6-Mercaptopurine and methotrexate intrathecally. After Induction therapy, all patients received intensification therapy with high-dose methotrexate followed by Pegaspargase. After intensification therapy,patients received consolidation(cytarabine, etoposide,Pegaspargase,dexamethasone,vincristine,cyclophosphamide,daunorubicin,thioguanine)and maintenance therapy(vincristine,6-mercaptopurine,methotrexate ,prednisone). Intrathecal methotrexate and intrathecal cytarabine were given as CNS prophylaxis. | Drug: Vincristine<br>* induction therapy I：1.4 mg/m2 IV d1, 8, 15, 22； consolidation therapy(Cycle 1)：1.4 mg/m2 IV d1, 8, 15, 22； Maintenance therapy: 1.4 mg/m2 intravenously every 3 months for a total of 2.5 years<br>* Other names: Vincasar;Drug: Daunorubicin<br>* induction therapy I：60 mg/m2 IV d1, 8, 15, 22； consolidation therapy(Cycle 3)：25 mg/m2 IV d1, 8, 15, 22；<br>* Other names: Cerubidine;Drug: Pegaspargase<br>* induction therapy I: 2500U/m2,im,d8,22 Intensification therapy:2500U/m2 im, d2,23 consolidation therapy(Cycle 2，4)：2500U/m2 im, d1<br>* Other names: Oncaspar;Drug: Prednisone<br>* induction therapy I：60 mg/m2 PO d1-28; Maintenance therapy:prednisone 60 mg/m2 orally for 5 days every 3 months for a total of 2.5 years<br>* Other names: Prednisone acetate;Drug: Intrathecal Methotrexate<br>* induction therapy I：12.5 mg IT d15 induction therapy II：12.5 mg IT d1, 8, 15, 22<br>* Other names: Rheumatrex;Drug: Cyclophosphamide<br>* induction therapy II:650 mg/m2 IV d1, 15, 29 consolidation therapy(Cycle 3)：650 mg/m2 IV，d29<br>* Other names: Cytoxan;Drug: Cytarabine<br>* induction therapy II:75 mg/m2 IV d1-4, 8-11, 15-18, 22-25 consolidation therapy(Cycle 1，2，4)：75 mg/m2 intravenously on days 1 to 5 consolidation therapy(Cycle 3):75 mg/m2 intravenously on days 31 to 34 and 38 to 41<br>* Other names: Cytosar-U;Drug: 6-Mercaptopurine<br>* induction therapy II:60 mg/m2 PO d1-28 Maintenance therapy:75 mg/m2 orally each day for a total of 2.5 years<br>* Other names: Purinethol;Drug: Methotrexate<br>* Intensification therapy:3 g/m2 intravenously given on days 1, 8, and 22 Maintenance therapy:20 mg/m2 orally or intravenously once a week for a total of 2.5 years.<br>* Other names: Rheumatrex;Drug: Etoposide<br>* consolidation therapy(Cycle 1，2，4)：100 mg/m2 intravenously on days 1 to 5<br>* Other names: VePesid;Drug: dexamethasone<br>* consolidation therapy(Cycle 1)：10mg/m2 orally on days 1 to 28<br>* Other names: Dexamethasone Sodium;Drug: thioguanine<br>* consolidation therapy(Cycle 3): 60 mg/m2 orally on days 29 to 42<br>* Other names: 6-TG;Drug: intrathecal cytarabine<br>* 50 mg intrathecal cytarabine was given on 4 occasions 3 months apart during maintenance therapy.<br>* Other names: Cytosar-U;|

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 |
| --- | --- | --- |
| overall survival |  | up to end of follow-up-phase (approximately 3 years) | 
| complete remission rate |  | every 4 weeks,up to completion of induction treatment(approximately 2months) | 
| Incidence of Treatment-Emergent Adverse Events classified according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) | including hematological safety and non-hematological safety. | up to end of follow-up-phase (approximately 3 years) | 
| Minimal Residual Disease (MRD) monitoring | Minimal residual disease is measured in bone marrow using an multiparameter flow cytometry.For the patients who achieved complete remission after induction therapy, if two consecutive tests for MRD were positive,we will define it as MRD positive | During treatment at time point 4, 8, 12, 16,20,24, 28 weeks（every 4 weeks,up to completion of consolidation therapy）and 40，52，64，76，88，100，112，124 weeks( every 12 weeks during maintenance therapy,up to the end of treatment ) |