Modified MRCUKALLⅫ/ECOGE2993 Regimen for ALL

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: January 2019

Detailed Description

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.

Interventions

  • Drug: Vincristine
    • 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
  • Drug: Daunorubicin
    • induction therapy I:60 mg/m2 IV d1, 8, 15, 22; consolidation therapy(Cycle 3):25 mg/m2 IV d1, 8, 15, 22;
  • Drug: Pegaspargase
    • induction therapy I: 2500U/m2,im,d8,22 Intensification therapy:2500U/m2 im, d2,23 consolidation therapy(Cycle 2,4):2500U/m2 im, d1
  • Drug: Prednisone
    • 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
  • Drug: Intrathecal Methotrexate
    • induction therapy I:12.5 mg IT d15 induction therapy II:12.5 mg IT d1, 8, 15, 22
  • Drug: Cyclophosphamide
    • induction therapy II:650 mg/m2 IV d1, 15, 29 consolidation therapy(Cycle 3):650 mg/m2 IV,d29
  • Drug: Cytarabine
    • 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
  • Drug: 6-Mercaptopurine
    • induction therapy II:60 mg/m2 PO d1-28 Maintenance therapy:75 mg/m2 orally each day for a total of 2.5 years
  • Drug: Methotrexate
    • 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.
  • Drug: Etoposide
    • consolidation therapy(Cycle 1,2,4):100 mg/m2 intravenously on days 1 to 5
  • Drug: dexamethasone
    • consolidation therapy(Cycle 1):10mg/m2 orally on days 1 to 28
  • Drug: thioguanine
    • consolidation therapy(Cycle 3): 60 mg/m2 orally on days 29 to 42
  • Drug: intrathecal cytarabine
    • 50 mg intrathecal cytarabine was given on 4 occasions 3 months apart during maintenance therapy.

Arms, Groups and Cohorts

  • Experimental: Modified MRCUKALLⅫ/ECOGE2993 Regimen
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • progression free survival
    • Time Frame: up to end of follow-up-phase (approximately 3 years)

Secondary Measures

  • overall survival
    • Time Frame: up to end of follow-up-phase (approximately 3 years)
  • complete remission rate
    • Time Frame: 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)
    • Time Frame: up to end of follow-up-phase (approximately 3 years)
    • including hematological safety and non-hematological safety.
  • Minimal Residual Disease (MRD) monitoring
    • Time Frame: 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 )
    • 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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 35 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Sun Yat-sen University
  • Provider of Information About this Clinical Study
    • Principal Investigator: dr. luyue, professor – Sun Yat-sen University
  • Overall Official(s)
    • yue lu, MD., Principal Investigator, Department of Hematological Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China
  • Overall Contact(s)
    • hua wang, MD., 0086-02087342438, wanghua@sysucc.org.cn

Citations Reporting on Results

Rowe JM, Buck G, Burnett AK, Chopra R, Wiernik PH, Richards SM, Lazarus HM, Franklin IM, Litzow MR, Ciobanu N, Prentice HG, Durrant J, Tallman MS, Goldstone AH; ECOG; MRC/NCRI Adult Leukemia Working Party. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005 Dec 1;106(12):3760-7. Epub 2005 Aug 16.

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