Rituximab Plus Chemotherapy for CD20+ Adult Acute Lymphoblastic Leukemia

Sponsor

Ruijin Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01358253

Collaborator

(none)

100

Enrollment

Location

Arms

Duration (Months)

4.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study is to evaluate the safety and efficacy of Rituximab combined with chemotherapy in CD20+ adult acute lymphoblastic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia	Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Dexamethasone Drug: Cytarabine Drug: Methotrexate Drug: Rituximab Drug: 6-Mercaptopurine Drug: Prednisone Drug: L-asparaginase	Phase 4

Detailed Description

Acute lymphoblastic leukemia (ALL) is a group of biologically heterogeneous diseases with diverse prognosis. Novel strategies for adult ALL have approached a CR rate of over 80%, which is similar to pediatric ALL. But the long term survival of adult ALL is only 30%-40%, much lower than pediatric patients.

In our trial, all the patients will first receive Vincristine 1.4mg/m2, max 2mg IV days 1,8,15,22, Daunorubicin 45mg/m2 IV days 1-3,Cyclophosphamide 750mg/m2 IV day 1 and prednisone 40-60mg/m2,by mouth days 1-14 (VDCP)regimen as initial induction therapy. If patients achieve complete remission after induction, they will be enrolled in our study for further consolidation and maintenance. If the tumor cells in bone marrow remain 5% to 20% after induction, the patients will receive VDCLP(VDCP+L-asparaginase 6000IU/m2 IV days5,7,9,11,13) and be enrolled until complete remission.

Rituximab is the main experimental intervention in our study.The consolidation regimen is HyperCVAD/MA or R-HyperCVAD/MA for totally 8 courses. The maintenance regimen includes 6-Mercaptopurine+Methotrexate for 24 months, Vincristine+Prednisone for the first 12 months, L-asparaginase in month 3 and 9 with or without Rituximab in month 6 and 12.

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Prospective Study of Rituximab Combined With Chemotherapy for CD20+ Adult Acute Lymphoblastic Leukemia

Study Start Date :

Dec 1, 2010

Actual Primary Completion Date :

Dec 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: HyperCVAD Consolidation: HyperCVAD(odd courses) alternated with high-dose methotrexate + cytarabine (even courses) every 21 days or later to allow for myelosuppression recovery, for total of 8 courses. Maintenance: 6-Mercaptopurine+Methotrexate for 24 months. Vincristine+Prednisone for the first 12 months. L-asparaginase in month 3 and 9.	Drug: Cyclophosphamide 300 mg/m2 IV over 3 hours every 12 hours x 6 doses days 1, 2, 3 (total dose 1800 mg/m2)(odd courses). Drug: Doxorubicin 50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses). Drug: Vincristine Consolidation:1.4 mg/m2 (max 2mg) IV on day 4 and day 11 (odd courses). Maintenance:1.4mg/m2(max 2mg) IV monthly from 1st to 12th month. Drug: Dexamethasone 40mg IV or by mouth (P.O.) daily days 1-4 and days 11-14(odd courses) Drug: Cytarabine 2g/m2 IV over 2 hours every 12 hours for 4 doses on days 2, 3 (even courses). Drug: Methotrexate Consolidation:1000 mg/m2 IV over 24 hours on day 1 (even courses). Maintenance:25mg/m2 weekly for 24 months. Drug: 6-Mercaptopurine Maintenance:60mg/m2 daily for 24 months. Drug: Prednisone Maintenance:40mg/m2 from days 1-7 monthly from 1st to 12th month. Drug: L-asparaginase Maintenance:6000IU/m2 IV on days 1,3,5 of the 3rd and 9th month.
Experimental: R-HyperCVAD Consolidation: R-HyperCVAD(odd courses) alternated with high-dose methotrexate + cytarabine (even courses) every 21 days or later to allow for myelosuppression recovery, for total of 8 courses. Maintenance: 6-Mercaptopurine+Methotrexate for 24 months. Vincristine+Prednisone for the first 12 months. L-asparaginase in month 3 and 9. Rituximab in month 6 and 12.	Drug: Cyclophosphamide 300 mg/m2 IV over 3 hours every 12 hours x 6 doses days 1, 2, 3 (total dose 1800 mg/m2)(odd courses). Drug: Doxorubicin 50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses). Drug: Vincristine Consolidation:1.4 mg/m2 (max 2mg) IV on day 4 and day 11 (odd courses). Maintenance:1.4mg/m2(max 2mg) IV monthly from 1st to 12th month. Drug: Dexamethasone 40mg IV or by mouth (P.O.) daily days 1-4 and days 11-14(odd courses) Drug: Cytarabine 2g/m2 IV over 2 hours every 12 hours for 4 doses on days 2, 3 (even courses). Drug: Methotrexate Consolidation:1000 mg/m2 IV over 24 hours on day 1 (even courses). Maintenance:25mg/m2 weekly for 24 months. Drug: Rituximab Consolidation:375 mg/m2 IV day 1 for the odd courses of therapy (total 4 times). Maintenance:375 mg/m2 IV in 6th month and 12th month. Drug: 6-Mercaptopurine Maintenance:60mg/m2 daily for 24 months. Drug: Prednisone Maintenance:40mg/m2 from days 1-7 monthly from 1st to 12th month. Drug: L-asparaginase Maintenance:6000IU/m2 IV on days 1,3,5 of the 3rd and 9th month.

Arm

Intervention/Treatment

Active Comparator: HyperCVAD

Consolidation: HyperCVAD(odd courses) alternated with high-dose methotrexate + cytarabine (even courses) every 21 days or later to allow for myelosuppression recovery, for total of 8 courses. Maintenance: 6-Mercaptopurine+Methotrexate for 24 months. Vincristine+Prednisone for the first 12 months. L-asparaginase in month 3 and 9.

Drug: Cyclophosphamide

300 mg/m2 IV over 3 hours every 12 hours x 6 doses days 1, 2, 3 (total dose 1800 mg/m2)(odd courses).

Drug: Doxorubicin

50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses).

Drug: Vincristine

Consolidation:1.4 mg/m2 (max 2mg) IV on day 4 and day 11 (odd courses). Maintenance:1.4mg/m2(max 2mg) IV monthly from 1st to 12th month.

Drug: Dexamethasone

40mg IV or by mouth (P.O.) daily days 1-4 and days 11-14(odd courses)

Drug: Cytarabine

2g/m2 IV over 2 hours every 12 hours for 4 doses on days 2, 3 (even courses).

Drug: Methotrexate

Consolidation:1000 mg/m2 IV over 24 hours on day 1 (even courses). Maintenance:25mg/m2 weekly for 24 months.

Drug: 6-Mercaptopurine

Maintenance:60mg/m2 daily for 24 months.

Drug: Prednisone

Maintenance:40mg/m2 from days 1-7 monthly from 1st to 12th month.

Drug: L-asparaginase

Maintenance:6000IU/m2 IV on days 1,3,5 of the 3rd and 9th month.

Experimental: R-HyperCVAD

Consolidation: R-HyperCVAD(odd courses) alternated with high-dose methotrexate + cytarabine (even courses) every 21 days or later to allow for myelosuppression recovery, for total of 8 courses. Maintenance: 6-Mercaptopurine+Methotrexate for 24 months. Vincristine+Prednisone for the first 12 months. L-asparaginase in month 3 and 9. Rituximab in month 6 and 12.

Drug: Cyclophosphamide

300 mg/m2 IV over 3 hours every 12 hours x 6 doses days 1, 2, 3 (total dose 1800 mg/m2)(odd courses).

Drug: Doxorubicin

50 mg/m2 IV over 2-24 hours via CVC on day 4 after last dose of cyclophosphamide given (odd courses).

Drug: Vincristine

Consolidation:1.4 mg/m2 (max 2mg) IV on day 4 and day 11 (odd courses). Maintenance:1.4mg/m2(max 2mg) IV monthly from 1st to 12th month.

Drug: Dexamethasone

40mg IV or by mouth (P.O.) daily days 1-4 and days 11-14(odd courses)

Drug: Cytarabine

2g/m2 IV over 2 hours every 12 hours for 4 doses on days 2, 3 (even courses).

Drug: Methotrexate

Consolidation:1000 mg/m2 IV over 24 hours on day 1 (even courses). Maintenance:25mg/m2 weekly for 24 months.

Drug: Rituximab

Consolidation:375 mg/m2 IV day 1 for the odd courses of therapy (total 4 times). Maintenance:375 mg/m2 IV in 6th month and 12th month.

Drug: 6-Mercaptopurine

Maintenance:60mg/m2 daily for 24 months.

Drug: Prednisone

Maintenance:40mg/m2 from days 1-7 monthly from 1st to 12th month.

Drug: L-asparaginase

Maintenance:6000IU/m2 IV on days 1,3,5 of the 3rd and 9th month.

Outcome Measures

Primary Outcome Measures

CR duration [After two 21-day courses]
Bone marrow MRD examination every two months
disease free survival [2 year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of CD20-positive ALL
Adequate liver function (bilirubin less than or equal to 1.5ULN, unless considered due to tumor), and renal function (creatinine less than or equal to 1.5ULN, unless considered due to tumor)
Signed informed consent