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

This study has been terminated.
(SBI Biotech who provided the drug for this study has decided to no longer support the study or GNKG168.)
Sponsor:
Information provided by (Responsible Party):
Nobuko Hijiya, MD, Therapeutic Advances in Childhood Leukemia Consortium
ClinicalTrials.gov Identifier:
NCT01743807
First received: November 28, 2012
Last updated: August 27, 2014
Last verified: August 2014

November 28, 2012
August 27, 2014
November 2012
July 2014   (final data collection date for primary outcome measure)
Number of patients with dose limiting toxicity (DLT). [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01743807 on ClinicalTrials.gov Archive Site
  • To measure the reduction of MRD in patients treated with GNKG168. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • To measure the length or remission in patients who receive GNKG168. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • To measure the rate of Graft Versus Host Disease (GVHD) in patient with previous HSCT. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • To measure the rate graft failure in patients who previously had a HSCT and who received GNKG168. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Phase I Study of GNKG168 in Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia
A Phase I Study of GNKG168 in Pediatric Patients With Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia (IND#113600)

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). GNKG168 is a Toll-like receptor (TLR) agonist. TLR agonists are a novel approach to stimulate an effective anti-tumor immune response as they are able to stimulate both innate and adaptive immune responses. There will be two strata i.e patients who have received hematopoietic stem cell transplant (HSCT) and patients who have never undergone HSCT. GNKG168 will be administered as a 60 min iv infusion. One 14-day cycle consists of 5-day treatment followed by 9 day-rest. Patients will receive 2 cycles before evaluation. The primary objective is to determine the maximum tolerated dose of GNKG168 in relapsed ALL and AML patients.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Relapsed Acute Lymphoblastic Leukemia
  • Relapsed Acute Myelogenous Leukemia
Drug: GNKG168
GNKG168 will be given intravenously over 1 hour on days 1 through 5 followed by 9 days of rest. Dose will be assigned at study entry.
  • Experimental: Dose Level 1
    GNKG168 0.25 mg/kg/day on days 1 through 5
    Intervention: Drug: GNKG168
  • Experimental: Dose Level 2
    GNKG168 0.75 mg/kg/day on days 1 through 5
    Intervention: Drug: GNKG168
  • Experimental: Dose Level 3
    GNKG168 1.5 mg/kg/day on days 1 through 5
    Intervention: Drug: GNKG168
  • Experimental: Dose Level 0
    If dose level #1 is too toxic the study will back down to dose level 0. GNKG168 0.15 mg/kg/day on days 1 through 5.
    Intervention: Drug: GNKG168
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
4
March 2015
July 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must be ≥1 and ≤ 21 years of age when originally diagnosed with ALL or AML.
  • Diagnosis

    1. Patients must have previously histologically confirmed ALL or AML at original diagnosis or previous relapse.
    2. Patients must be in complete remission (CR) with less than 5% blasts in the bone marrow.
  • Post-HSCT patients should be in first or greater CR
  • Patients who have never received HSCT should be in second or greater CR c. Patient must have detectable MRD (≥0.01%) by flow cytometry as confirmed by Brent Woods' lab. Results must be available at the time of enrollment.
  • Karnofsky ≥ 50% for patients >16 years of age and Lansky ≥ 50% for patients ≤16 years of age. (See Appendix I for Performance Scales)
  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy.
  • At least 14 days must have elapsed since any treatment with systemic chemotherapy including high-dose steroid (prednisone>0.5 mg/kg or equivalent), radiotherapy, biological therapy or any other investigational therapy. (Note: low-dose steroid; prednisone ≤0.5 mg/kg/day or equivalent is allowed.)
  • Patients who have never had a Hematopoietic Stem Cell Transplant (HSCT) must not be a suitable candidate for HSCT.
  • Previous Hematopoietic Stem Cell Transplant:

    1. Patients having received HSCT are eligible.
    2. Patients having received donor lymphocyte infusions (DLI) are eligible.
    3. At least 60 days must have elapsed from the last DLI.
    4. Must have ≥95% donor T-cell chimerism.
    5. Patients must have been off all immune suppression drugs for 7 days before study entry. (at least 2 weeks for high-dose steroid, i.e. prednisone>0.5 mg/kg or equivalent; see section 3.3.4 b) (Note; low-dose steroid; prednisone ≤0.5 mg/kg/day or equivalent is allowed.)
  • Patients must have a serum creatinine that is less than or equal to 1.5 x the institutional upper limit of normal according to age.
  • Patient's alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be less than or equal to 3 x institutional upper limit of normal.
  • Patient's total bilirubin must be less than or equal to 1.5 x institutional upper limit of normal.
  • Patient must have a shortening fraction > 27% or an ejection fraction > 45% by echocardiogram (ECHO) or multigated radionuclide angiography (MUGA) .
  • Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.
  • Female patients with infants must agree not to breastfeed their infants while on this study.
  • Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study.
  • Patients must have an absolute neutrophil count > 1000/dL, platelets > 100,000/dL AND absolute lymphocyte count > 200 which is not decreasing. Patients with previous HSCT may have a platelet count > 50,000/dL.

Exclusion Criteria:

  • Active grade 2 or higher acute GVHD at the time of study entry.
  • Active chronic GVHD (moderate or severe). See Appendix 2 for Chronic GVHD Grading.
  • Plan for donor lymphocyte infusions during the study period.
  • Need for immunosuppressive medications including high-dose corticosteroids (prednisone >0.5 mg/kg or equivalent) (Note: low-dose steroid; prednisone ≤0.5 mg/kg/day or equivalent is allowed.)
  • Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
  • Patient will be excluded if they are currently receiving other investigational drugs.
  • Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
  • Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the prescribed protocol therapy, interfere with consent, study participation, follow up, or interpretation of study results.
  • Patients with central nervous system 3 disease are excluded.
Both
1 Year to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01743807
T2009-008
Yes
Nobuko Hijiya, MD, Therapeutic Advances in Childhood Leukemia Consortium
Therapeutic Advances in Childhood Leukemia Consortium
Not Provided
Study Chair: Nobuko Hijiya, MD Ann and Robert H Lurie Children's Hospital of Chicago
Study Chair: Kirk Schultz, MD British Columbia Children's Hospital
Therapeutic Advances in Childhood Leukemia Consortium
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP