Phase I Study of GNKG168 in Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia

DLT is defined as: A) Any non-hematologic toxicity that is ≥ CTCAE grade 3 and at least possibly related to GNKG168 (the relationship to GNKG168 cannot be ruled out), with the EXCEPTION of the following toxicities when observed at Grade 3: * Fatigue * Fever * Anorexia * Rash that turns to grade ≤ 2 within 7 days * Elevation in hepatic transaminases (ALT/SGOT and AST/SGPT), GGT or alkaline phosphatase that returns to ≤ grade 2 within 14 days. It will not be considered a DLT if the patient exits the study and begins alternative therapy before the end of the 14 day evaluation period. B) Grade 3 or 4 hematologic toxicity that is at least possibly related to GNKG168 that does not reverse to baseline within 7 days. C) For patients who have undergone HSCT, DLT will include the onset of Grade 3 or 4 acute GVHD, the onset of moderate to severe chronic GVHD, the onset of bronchiolitis obliterans and graft failure.

Time frame: Beginning with the first dose of GNKG168 until the end of course 2; courses are 14 days so there will be approximately 28 days of monitoring for DLT

Population: Immunomodulatory molecules were examined at two time points. Analyses were limited to the pretreatment and first post treatment samples. Additional samples were excluded from the analysis. A paired t-test was performed to examine the effect of first treatment on the expression of each gene in the CodeSet. Significance was declared at a nominal p-value threshold of 0.05. We note that this liberal p-value threshold was chosen due to the limited sample size.

Change in the percent of ALL or AML blasts exhibiting markers of immunogenicity and apoptosis will be analyzed from bone marrow specimens.

Time frame: End of Course 1 (Day 14), end of Course 2 (approx. Day 28), end of courses 4 and 6 (approx. Days 56 and 70), and date removed from therapy if previous marrow sample > 2 weeks ago

Population: Study terminated early and the variable was not analyzed.

* MRD negative Complete Remission : Negative MRD (\<0.01%), no evidence of circulating leukemic blasts or extramedullary disease, and recovery of peripheral counts (ANC ≥ 500/µL and PLT count ≥ 50,000 µL). * MRD negative Complete Remission without platelet recovery: Insufficient recovery of platelets (\< 50,000/ µL) but otherwise meets the criteria of MRD-CR. * Stable Disease: Patient does not satisfy the criterion for PD, or has recovery of ANC ≥ 500/µL and fails to qualify for MRD-CR or MRD-CRp. * Progressive Disease: At least 5% of circulating leukemic cells or ≥5% in a marrow with count recovery, development of new sites of extramedullary disease, or other laboratory or clinical evidence of PD, with or without recovery of ANC or platelets. * Not evaluable: Patient does not satisfy the criterion for PD, and did not have a marrow evaluation, had inadequate marrow cell count, or had insufficient recovery of ANC for MRD-CR, MRD-CRp or SD classification.

Time frame: Until patient is no longer being followed (off study)

Population: Study terminated early and the variable was not analyzed.

Peripheral blood samples will be evaluated for the presence of cGVHD biomarkers. Change in level of MRD, and MRD response following GNKG168

Time frame: Day 14

Population: Study terminated early and the variable was not analyzed.

We will evaluate the impact of GNKG168 on induction of clinical GVHD using the consensus scoring system developed by NIH (Filipovich et. al., National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report, Biology of Blood and Marrow Transplantation, Volume 11, Issue 12, Dec. 2005, pp. 945-956)

Time frame: Weekly during Courses 1 and 2 (i.e, 4 times in 28 days), Day 1 of Courses 3-6 (approximately Days 29, 43 and 57), and when patient is removed from protocol therapy.

Population: 2 HSCT patients enrolled in dose level #1,one of the patients never began treatment as was no longer eligible for treatment due to peripheral blasts. Therefore 1 patient was enrolled and completed treatment at dose level 1. There were 2 Non-HSCT patients enrolled at dose level 1 who completed the treatment.

Doctors have developed a test to detect very small amounts of leukemia that still exist even though it looks like remission under a microscope. This test is called Minimal Residual Disease (MRD). MRD is very specific and can detect 1 cancer cell out of 10,000 regular cells. The results of the MRD test on bone marrow can show when a patient has a very small amount of cancer cells left in the bone marrow. We will use this test to evaluate the effect of GNKG168 in killing the small amount of cells left in your bone marrow.

Time frame: Pre-study and End of Course 1 (Day 14)

Population: Patients who had MRD analyzed at both the pre-study event and end of course 1.