This is a multi-center, phase I/II clinical trial for patients who have relapsed more than 60 day after allogeneic transplant for a hematologic malignancy. The study consists of two phases. The dose finding phase is a modified version of a phase I trial and the extended phase is a modified version of a phase II trial. The primary objective of the dose finding phase is to determine the maximum tolerated, minimum efficacious dose (MTD/MED) of a interleukin-15 (IL-15) super agonist complex (ALT-803) when given once weekly for 4 weeks in the outpatient setting. The study will follow a standard 3+3 design of dose escalation for toxicity with an added feature of stopping early if efficacy is confirmed. There are six dose levels of ALT-803 for to determine the MTD/MED: 1, 3, 6, 10, 20, and 30 mcg/kg. Once the MTD/MED for ALT-803 is determined, this cohort will be used in the extended phase. The primary goal of this extended phase is to study the potential efficacy of ALT-803 in this patient population. Efficacy will be measured using rates of remission induction. An optimal Simon's two-stage design will be used in this phase. Stage 1 will enroll 14 patients (including the 6 patients treated at the MTD/MED during the dose finding phase). If 3 or more of these 14 patients respond to ALT-803, the trial will move to stage 2 and enroll an additional 23 patients. If 2 or fewer respond, the study will terminate enrollment early.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Given weekly IV at assigned dose level, ranging from 1mcg/kg to 30mcg/kg.
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
Washington University
St Louis, Missouri, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Number of Participants With Dose Limiting Toxicity (DLT) Events
The Dose Limiting Toxicity (DLT) is defined as (during first treatment cycle only): * any treatment-emergent grade 3 non-hematologic toxicity lasting more than 48 hours (refer to section 6.2.1.1 for full definition) * any treatment-emergent grade 4 or 5 non-hematologic toxicity of any duration * grade III or IV acute GVHD within 6 weeks after the first ALT-803 dose Maximum Tolerated Dose (MTD) is defined as the dose level where ≤ 1 out of 6 patients has DLT during the first treatment cycle
Time frame: 4 weeks
Number of Participants Experiencing Potential Efficacy of ALT 803
The potential efficacy of ALT-803 in this patient population is measured by the responses based on bone marrow examination 1 and 3 months after the last dose of ALT-803. Response was defined as follows: for AML and myelodysplastic syndromes (MDS) using the International Working Group modified criteria, non-Hodgkin lymphoma, and multiple myeloma using the International Myeloma Working Group Uniform Response Criteria, and acute lymphoblastic leukemia using protocol-specified criteria.
Time frame: 4 months
Number of Participants With Excessive Toxicity
To evaluate the safety of the ALT-803 when administered on this schedule. Excessive toxicity is defined as having a grade 3-5 non-hematologic, non-relapse and non-infectious toxicity (except fevers alone) based on the NCI's CTCAE version 4.
Time frame: 4 weeks
Number of Participants With Incidence of Acute Graft Versus Host Disease
Time frame: 100 days
Number of Participants With Incidence of Chronic Graft Versus Host Disease
Time frame: 1 year
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