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NCT01743807

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

Terminated Phase 1 Results posted Last updated 27 January 2025
What this trial tests

Phase 1 trial testing GNKG168 in Relapsed Acute Lymphoblastic Leukemia in 4 participants. Terminated before completion.

Timeline
26 March 2014
Primary endpoint
28 July 2014
28 July 2014

Quick facts

Lead sponsorTherapeutic Advances in Childhood Leukemia Consortium
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment4
Start date26 March 2014
Primary completion28 July 2014
Estimated completion28 July 2014
Sites3 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Therapeutic Advances in Childhood Leukemia Consortium

Who can join

Adults 1 to 21, any sex, with Relapsed Acute Lymphoblastic Leukemia or Relapsed Acute Myelogenous Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Patients With Dose Limiting Toxicity (DLT) in the First Two Courses of Therapy Primary · 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

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

GroupValue95% CI
Post HSCT- Dose Level 00
Post HSCT- Dose Level 10
Post HSCT- Dose Level 20
Post HSCT- Dose Level 30
No HSCT- Dose Level 00
No HSCT- Dose Level 10
No HSCT- Dose Level 20
No HSCT- Dose Level 30
The Number of Participants With a Decrease in Minimal Residual Disease (MRD) Present in Patients Treated With GNKG168 Secondary · Pre-study and End of Course 1 (Day 14)

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.

GroupValue95% CI
HSCT- Dose Level 00
HSCT- Dose Level 10
HSCT- Dose Level 20
HSCT- Dose Level 30
No HSCT- Dose Level 00
No HSCT- Dose Level 10
No HSCT- Dose Level 20
No HSCT- Dose Level 30
Occurrence of Graft Versus Host Disease (GVHD) in Patients Who Had Previous HSCT and Received GNKG168 Secondary · 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.

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)

GroupValue95% CI
HSCT- Dose Level 00
HSCT- Dos level10
HSCT- Dose Level 20
HSCT- Dose Level 30
No HSCT- Dose Level 00
No HSCT- Dose Level 10
No HSCT- Dose Level 20
No HSCT- Dose Level 30

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs were collected from the first dose of study therapy until 30 days after the last dose of study therapy. Therefore, for a given patient, AEs could be captured for 30-114 days depending on the length of time the patient received therapy.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

HSCT-Dose Level 0
Serious: 0
Deaths: 0
HSCT-Dose Level 1
Serious: 0/1 (0%)
Deaths: 0/1
HSCT-Dose Level 2
Serious: 0
Deaths: 0
HSCT-Dose Level 3
Serious: 0
Deaths: 0
No HSCT-Dose Level 0
Serious: 0
Deaths: 0
No HSCT-Dose Level 1
Serious: 1/2 (50%)
Deaths: 0/2
No HSCT-Dose Level 2
Serious: 0
Deaths: 0
No HSCT-Dose Level 3
Serious: 0
Deaths: 0

Serious adverse events (1 terms)

ReactionSystemHSCT-Dose Level 0HSCT-Dose Level 1HSCT-Dose Level 2HSCT-Dose Level 3No HSCT-Dose Level 0No HSCT-Dose Level 1No HSCT-Dose Level 2No HSCT-Dose Level 3
Febrile neutropeniaBlood and lymphatic system disorders
Other adverse events (17 terms — click to expand)

ReactionSystemHSCT-Dose Level 0HSCT-Dose Level 1HSCT-Dose Level 2HSCT-Dose Level 3No HSCT-Dose Level 0No HSCT-Dose Level 1No HSCT-Dose Level 2No HSCT-Dose Level 3
Platelet count decreasedInvestigations
Alanine aminotransferase increasedInvestigations
AnemiaBlood and lymphatic system disorders
Aspartate aminotransferase increasedInvestigations
Creatinine increasedInvestigations
DyspepsiaGastrointestinal disorders
Edema limbsGeneral disorders
HypercalcemiaInvestigations
HyperglycemiaMetabolism and nutrition disorders
HyperkalemiaInvestigations
HypertensionVascular disorders
HypokalemiaInvestigations
NauseaGastrointestinal disorders
PainGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Renal and urinary disorders - Other, specifyRenal and urinary disorders
White blood cell decreasedInvestigations

Most-reported serious reactions: Febrile neutropenia.

Data from ClinicalTrials.gov NCT01743807 adverse events section.

Sponsor's own description

This is a phase I trial of an investigational drug called GNKG168 in patients with relapsed and refractory acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML) who are in morphologic remission but are positive for Minimum Residual Disease (MRD).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Recent clinical trends in Toll-like receptor targeting therapeutics.
    Anwar MA, Shah M, Kim J, Choi S. · · 2019 · cited 209× · PMID 30450666 · DOI 10.1002/med.21553
  2. Recent Advances in Oligonucleotide Therapeutics in Oncology.
    Xiong H, Veedu RN, Diermeier SD. · · 2021 · cited 132× · PMID 33804856 · DOI 10.3390/ijms22073295
  3. Trial Watch: Toll-like receptor agonists for cancer therapy.
    Vacchelli E, Eggermont A, Sautès-Fridman C, Galon J, et al · · 2013 · cited 127× · PMID 24083080 · DOI 10.4161/onci.25238
  4. Trial Watch: Immunostimulation with Toll-like receptor agonists in cancer therapy.
    Iribarren K, Bloy N, Buqué A, Cremer I, et al · · 2016 · cited 98× · PMID 27141345 · DOI 10.1080/2162402x.2015.1088631
  5. Inflammatory Signaling Pathways in Preleukemic and Leukemic Stem Cells.
    Hemmati S, Haque T, Gritsman K. · · 2017 · cited 82× · PMID 29181334 · DOI 10.3389/fonc.2017.00265
  6. CpG Oligodeoxynucleotides for Anticancer Monotherapy from Preclinical Stages to Clinical Trials.
    Zhang Z, Kuo JC, Yao S, Zhang C, et al · · 2021 · cited 58× · PMID 35056969 · DOI 10.3390/pharmaceutics14010073
  7. Pattern recognition receptors: function, regulation and therapeutic potential.
    Chen R, Zou J, Chen J, Zhong X, et al · · 2025 · cited 53× · PMID 40640149 · DOI 10.1038/s41392-025-02264-1
  8. The Latest Approach of Immunotherapy with Endosomal TLR Agonists Improving NK Cell Function: An Overview.
    Veneziani I, Alicata C, Moretta L, Maggi E. · · 2022 · cited 10× · PMID 36672572 · DOI 10.3390/biomedicines11010064

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