Phase I, open label, non-randomized, multicenter, prospective dose escalation study of F16IL2 in combination with very low-dose cytarabine in subjects with acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT).
Phase I, open label, non-randomized, multicenter, prospective dose escalation study of F16IL2 in combination with very low-dose cytarabine in subjects with acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT). The aim of the study is to determine a recommended dose for F16IL2 in AML relapse after alloHSCT and investigating the toxicity of the combination regimen. Patients will be enrolled sequentially in cohorts and treated at different dose levels of F16IL2 and a fixed dose of cytarabine. All patients first receive an initial run-in dose of 30 Mio IU of F16IL2 on day 1 and escalating doses of F16IL2 on day 1, 8, 15 and 22. Patients will be treated with cytarabine (5 mg twice daily s.c. for 10 days). The following F16IL2 administration will be at the dose of the respective cohort (days 8, 15 and 22). The RD will be defined following a traditional 3+3 design. The dose escalation will continue until the MTD is found, that is until at least two patients among a cohort of three to six patients experience a dose limiting toxicity (DLT) (i.e., \>33 % of patients with a DLT). The RD is defined as the dose level just below the MTD level. If the MTD is not found at cohort 5 the RD for this study will be considered equal to the cohort 5 dosage.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
All patients first receive an initial run-in dose of 30 Mio IU of F16IL2 on day 1 and escalating doses of F16IL2 on day 1, 8, 15 and 22. Treatment will be repeated every 28 days for up to three cycles.
Patients will be treated with cytarabine (5 mg twice daily s.c. for 10 days). Treatment will be repeated every 28 days for up to three cycles.
Münster University Hospital
Münster, Germany
Dose limiting toxicity (DLT)
To assess the safety, including maximum tolerated dose (MTD), recommended dose (RD) and dose limiting toxicity (DLT) of F16IL2 combined with very low dose cytarabine, Adverse Events (AEs) assessment based on CTCAE v.4.03 will be considered.
Time frame: Safety assessment will be performed from Day 1 up to Day 28 of the Cycle 1 (each cycle is 28 days)
The overall response rate (ORR, consisting of CR and CRi as defined by the International Working Group (IWG) criteria).
Time frame: Up to 13 months
The relapse-free survival (RFS) of responding (CR and CRi) patients.
Time frame: Up to 12 months
The time to response (CR or CRi) of responding patients.
Time frame: Up to 13 months
Median progression free survival (PFS)
Time frame: Up to 13 months
Median overall survival (OS)
Time frame: Up to 13 months
The time to complete donor chimerism.
Time frame: Up to 13 months
The rate to complete donor chimerism.
Time frame: Up to 13 months
The rate of acute GvHD.
Time frame: Up to 13 months
The rate of chronic GvHD.
The rate of patients with chronic GvHD will be summarized according to the following Chronic GVHD Staging: * mild: involvement of 1 to 2 organs/sites (except for lung) with a maximum score of 1; * moderate: involvement of at least 1 organ/site with a score of 2 or ≥ 3 organs/sites with a score of 1 or lung involvement with a score of 1; * severe: any organ/site with a score of 3 or lung involvement with a score of 2.
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Time frame: Up to 13 months
Human anti-fusion protein antibodies (HAFA) levels before and following treatment.
Time frame: at Day 1 (cycle 1), at Day 29 (cycle 2), Day 57 (cycle 3), from Day 25 to Day 85 (EoT visit), from Day 53 to Day 113 (first follow-up visit)