Modified MRCUKALLⅫ/ECOGE2993 Regimen for ALL

Sponsor

Sun Yat-sen University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02660762

Collaborator

(none)

100

Enrollment

Location

Arm

Duration (Months)

2.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukaemia,Lymphoblastic	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	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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 Start Date :

Jan 1, 2016

Anticipated Primary Completion Date :

Jan 1, 2019

Anticipated Study Completion Date :

Jan 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
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.	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 Other Names: Vincasar 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； Other Names: Cerubidine 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 Other Names: Oncaspar 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 Other Names: Prednisone acetate Drug: Intrathecal Methotrexate induction therapy I：12.5 mg IT d15 induction therapy II：12.5 mg IT d1, 8, 15, 22 Other Names: Rheumatrex Drug: Cyclophosphamide induction therapy II:650 mg/m2 IV d1, 15, 29 consolidation therapy(Cycle 3)：650 mg/m2 IV，d29 Other Names: Cytoxan 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 Other Names: Cytosar-U 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 Other Names: Purinethol 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. Other Names: Rheumatrex Drug: Etoposide consolidation therapy(Cycle 1，2，4)：100 mg/m2 intravenously on days 1 to 5 Other Names: VePesid Drug: dexamethasone consolidation therapy(Cycle 1)：10mg/m2 orally on days 1 to 28 Other Names: Dexamethasone Sodium Drug: thioguanine consolidation therapy(Cycle 3): 60 mg/m2 orally on days 29 to 42 Other Names: 6-TG Drug: intrathecal cytarabine 50 mg intrathecal cytarabine was given on 4 occasions 3 months apart during maintenance therapy. Other Names: Cytosar-U

Arm

Intervention/Treatment

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.

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

Other Names:

Vincasar

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；

Other Names:

Cerubidine

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

Other Names:

Oncaspar

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

Other Names:

Prednisone acetate

Drug: Intrathecal Methotrexate

induction therapy I：12.5 mg IT d15 induction therapy II：12.5 mg IT d1, 8, 15, 22

Other Names:

Rheumatrex

Drug: Cyclophosphamide

induction therapy II:650 mg/m2 IV d1, 15, 29 consolidation therapy(Cycle 3)：650 mg/m2 IV，d29

Other Names:

Cytoxan

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

Other Names:

Cytosar-U

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

Other Names:

Purinethol

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.

Other Names:

Rheumatrex

Drug: Etoposide

consolidation therapy(Cycle 1，2，4)：100 mg/m2 intravenously on days 1 to 5

Other Names:

VePesid

Drug: dexamethasone

consolidation therapy(Cycle 1)：10mg/m2 orally on days 1 to 28

Other Names:

Dexamethasone Sodium

Drug: thioguanine

consolidation therapy(Cycle 3): 60 mg/m2 orally on days 29 to 42

Other Names:

6-TG

Drug: intrathecal cytarabine

50 mg intrathecal cytarabine was given on 4 occasions 3 months apart during maintenance therapy.

Other Names:

Cytosar-U

Outcome Measures

Primary Outcome Measures

progression free survival [up to end of follow-up-phase (approximately 3 years)]

Secondary Outcome Measures

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) [up to end of follow-up-phase (approximately 3 years)]
including hematological safety and non-hematological safety.
Minimal Residual Disease (MRD) monitoring [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sun Yat-sen University Cancer Center	GuangZhou	Guangdong	China	510060

Sponsors and Collaborators

Sun Yat-sen University

Investigators

Principal Investigator: yue lu, MD., Department of Hematological Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China