The objective of this protocol is to improve survival for adults with acute lymphoblastic leukemia or acute lymphoblastic lymphoma by reducing systemic and central nervous system (CNS) relapse with acceptable toxicity using intensive chemotherapy with liposomal cytarabine (Depocyt®) CNS prophylaxis.
This treatment regimen builds on the "Linker" regimen/UCSF Protocol 8707 ALL regimen backbone with the goal of improved efficacy and acceptable toxicity by substituting pegylated asparaginase for native L-asparaginase, the addition of rituximab for pre-B-cell ALL, and the addition of dasatinib for Philadelphia chromosome/BCR-ABL positive ALL, and the addition of cyclophosphamide for younger adults. In addition, the study regimen aims to reduce CNS relapse through the use of intrathecal liposomal cytarabine in place of intrathecal methotrexate for CNS relapse prophylaxis and The regimen uses 3 modules of therapy with non-cross-resistant chemotherapy agents. Rituximab is added for a total of 8 doses for patients with pre-B-cell ALL. Dasatinib is added for patients with Ph+ ALL. Course 1A (Induction): Daunorubicin, vincristine, PEG-asparaginase, and prednisone for all patients with the addition of cyclophosphamide for patients 18-39 years of age. Treatment is intensified for patients with disease present on a day 14 bone marrow biopsies during Induction Course 1A. In addition to standard analyses, minimal residual disease will be assessed on day 14 and remission bone marrow aspirates and correlated with outcomes. Course 1B: High-dose methotrexate, oral 6-mercaptopurine, and PEG-asparaginase. Course 1C: High-dose cytarabine and etoposide. The 3 courses then repeat (2A (Intensification), 2B, 2C) followed by a final "B" cycle (3B) of high-dose methotrexate, 6-mercaptopurine, and PEG-asparaginase. After completion of Course 3B, patients proceed to maintenance chemotherapy with monthly methotrexate, vincristine, 6-mercaptopurine, and prednisone cycles for 24 months with a single dose PEG-asparaginase given in month 1 of Maintenance. CNS prophylaxis: Intrathecal liposomal cytarabine replaces intrathecal methotrexate CNS prophylaxis and is given every 2 weeks during the "A" Induction and Intensification courses then every 3 months during Maintenance for a total of 8 doses. Given the presence of CNS penetrating chemotherapy in the "B" and "C" cycles, intrathecal liposomal cytarabine is not given due to risk of excessive CNS toxicity. There is a randomization to hydrocortisone or placebo premedication prior to PEG-asparaginase.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
31
Daunorubicin 60 mg/m2 IV (in the vein) daily 1,2,3 Courses 1A, 2A
1.4 mg/m2 IV, days 1, 8, 15, 22 (cap at 2mg for ages \>50) during Courses 1A, 2A; Maintenance: Day 1 during months 2-12
2,000 IU/m2 IV for ages \</= 50, age \> 50, 1000 IU/m2 IV Day 16, Courses 1A \& 2A; Day 18, Course 1B; Day 17, Course 2B; Day 16, Maintenance, Month 1
UCSD, Division of Blood and Marrow Transplantation, Moores Cancer Center
La Jolla, California, United States
Hematological Malignancies/Stem Cell Transplantation Unit, David Geffen School of Medicine at UCLA
Los Angeles, California, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
UCSF Comprehensive Cancer Center
San Francisco, California, United States
Event-free survival
Time frame: 3-year
Liposomal cytarabine toxicity
Time frame: 3 years
CNS relapse rate
Time frame: 3-year
Overall survival
Time frame: 3-year
Leukemia-free survival
Time frame: 3-year
Efficacy of hydrocortisone premedication for reduced PEG-asparaginase allergic reactions
Time frame: 3 years
PEG-asparaginase toxicities
Time frame: 3 years
Complete and overall response rates
Time frame: 3 years
Non-relapse mortality
Time frame: 3-year
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
750 mg/m2 IV, days 1 \&15 for subjects \<40 year of age, substitute cyclophosphamide 500 mg/m2 IV over 60 minutes every 12 hours for 4 doses on days 15 \& 16 for subjects \< 40 years of age if day 14 bone marrow M2 or M3; Courses 1A \& 2A
60 mg/m2 orally once daily on days 1-28 during Courses 1A \& 2A; Maintenance: Monthly, days 1-5
25 mg intrathecal (IT), on days 1 \& 15 during Courses 1A \& 2A; 50 mg intrathecal on day 1 during Maintenance Months 1 through 4
220 mg/m2 IV bolus over 15 minutes then 60 mg/m2/hour for 36 hours once on days 2-3 and 16-17 during Courses 1B \& 2B; 20 mg/m2 orally one day per week every 7 days during Maintenance Months
50 mg/m2 IV over 15-30 minutes every 6 hours for 3 doses to begin immediately after completion of methotrexate infusion, then 10 mg/m2 orally or IV over 15-30 minutes every 6 hours until methotrexate level less than 0.1 micromolar during Courses 1B \& 2B
2,000 mg/m2 IV, days 1-4 during Courses 1C \& 2C
500 mg/m2 IV over 3 hours once daily on days 1-4 during Courses 1C \& 2C
140 mg orally daily if BCR/ABL positive and/or Ph+
375 mg/m2 IV once daily on days 1 \& 15 (precursor B-cell ALL only, administer per institutional protocol) during Courses 1A, 1B, 1C \& 2A
Randomize patients proceeding to Course 1B to hydrocortisone versus placebo prior to PEG-asparaginase treatments in Courses 1B, 2B, 3B, and Maintenance month 1