NCT02043587

Chemotherapy With Liposomal Cytarabine CNS Prophylaxis for Adult Acute Lymphoblastic Leukemia & Lymphoblastic Lymphoma

A Phase II Study of Punctual, Cyclic, and Intensive Chemotherapy With Liposomal Cytarabine (Depocyt®) CNS Prophylaxis for Adults With Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 31 (actual)
• Sponsor: University of California, San Diego · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Acute Lymphocytic Leukemia
• Adult Lymphoblastic Lymphoma

Interventions

Type	Name	Description
DRUG	DNR	Daunorubicin 60 mg/m2 IV (in the vein) daily 1,2,3 Courses 1A, 2A
DRUG	VCR	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
DRUG	PEG-asp	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
DRUG	CTX	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
DRUG	Prednisone	60 mg/m2 orally once daily on days 1-28 during Courses 1A \& 2A; Maintenance: Monthly, days 1-5
DRUG	Liposomal AraC	25 mg intrathecal (IT), on days 1 \& 15 during Courses 1A \& 2A; 50 mg intrathecal on day 1 during Maintenance Months 1 through 4
DRUG	MTX	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
DRUG	LCV	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
DRUG	AraC	2,000 mg/m2 IV, days 1-4 during Courses 1C \& 2C
DRUG	Etoposide	500 mg/m2 IV over 3 hours once daily on days 1-4 during Courses 1C \& 2C
DRUG	Dasatinib	140 mg orally daily if BCR/ABL positive and/or Ph+
DRUG	Rituximab	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
DRUG	Hydrocortisone	Randomize patients proceeding to Course 1B to hydrocortisone versus placebo prior to PEG-asparaginase treatments in Courses 1B, 2B, 3B, and Maintenance month 1

Timeline

• Start date: 2014-01-01
• Primary completion: 2022-04-14
• Completion: 2022-04-14
• First posted: 2014-01-23
• Last updated: 2022-05-02

Locations

4 sites across 1 country: United States