This phase II trial studies how well fludarabine phosphate, cytarabine, and asparaginase Erwinia chrysanthemi work in treating patients with hematologic malignancies. Drugs used in chemotherapy, such as fludarabine phosphate and cytarabine work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Biological therapies, such as asparaginase Erwinia chrysanthemi, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Giving fludarabine phosphate, cytarabine, and asparaginase Erwinia chrysanthemi may work better in treating patients with relapsed or refractory hematologic malignancies.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02718755.
PRIMARY OBJECTIVES:
I. To determine the overall response rate (complete remission [CR], partial remission [PR], or marrow leukemia free state [MLFS]) of fludarabine phosphate (fludarabine), high-dose cytarabine (araC), and asparaginase Erwinia chrysanthemi (Erwinase) in patients with relapsed and refractory hematologic malignancies.
SECONDARY OBJECTIVES:
I. To determine the safety and tolerability of fludarabine, high-dose araC, and Erwinase in patients with relapsed and refractory hematologic malignancies.
II. To assess overall survival (OS) and disease-free survival (DFS) of patients treated with fludarabine, high-dose araC, and Erwinase.
III. To assess the duration of response to the combination in patients with advanced hematologic malignancies.
TERTIARY OBJECTIVES:
I. Explore pretreatment and on-treatment biological correlates to predict sensitivity/resistance of Erwinase-based therapy as well as characterize its effect on oncogenic signaling networks.
OUTLINE:
INDUCTION PHASE: Patients receive fludarabine phosphate intravenously (IV) over 15-30 minutes and cytarabine IV over 2 hours on days 1-5. Patients also receive asparaginase Erwinia chrysanthemi IV over 90-120 minutes or intramuscularly (IM) on days 1-7. Treatment repeats every 28 days for up to 2 courses in absence of disease progression or unacceptable toxicity.
CONSOLIDATION PHASE: Patients receive fludarabine phosphate IV over 15-30 minutes and cytarabine IV over 2 hours on days 1-4. Patients also receive asparaginase Erwinia chrysanthemi IV over 90-120 minutes or IM every other day on days 1, 3, 5, 7, 9, 11, 13, and 15. Treatment repeats every 28 days for up to 3 courses in absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 4-8 weeks and 6-12 months.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorTapan M. Kadia
