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
  Purpose

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.


Condition Intervention Phase
Relapsed Acute Lymphoblastic Leukemia
Relapsed Acute Myelogenous Leukemia
Drug: GNKG168
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of GNKG168 in Pediatric Patients With Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia (IND#113600)

Resource links provided by NLM:


Further study details as provided by Therapeutic Advances in Childhood Leukemia Consortium:

Primary Outcome Measures:
  • Number of patients with dose limiting toxicity (DLT). [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 4
Study Start Date: November 2012
Estimated Study Completion Date: March 2015
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Level 1
GNKG168 0.25 mg/kg/day on days 1 through 5
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 2
GNKG168 0.75 mg/kg/day on days 1 through 5
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 3
GNKG168 1.5 mg/kg/day on days 1 through 5
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 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.
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.

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01743807

  Hide Study Locations
Locations
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States
United States, California
Miller Children's Hospital
Long Beach, California, United States
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
Oakland Children's Hospital
Oakland, California, United States
Stanford University Medical Center
Palo Alto, California, United States, 94304-1812
UCSF School of Medicine
San Francisco, California, United States, 94143-0106
United States, Colorado
The Children's Hospital, University of Colorado
Aurora, Colorado, United States, 80045
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States
United States, Florida
University of Miami Cancer Center
Miami, Florida, United States, 33136
United States, Georgia
Children's Healthcare of Atlanta, Emory University
Atlanta, Georgia, United States
United States, Illinois
Children's Memorial
Chicago, Illinois, United States
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States
United States, Massachusetts
Dana Farber
Boston, Massachusetts, United States
United States, Michigan
C.S. Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109-0914
United States, Minnesota
Childrens Hospital & Clinics of Minnesota
Minneapolis, Minnesota, United States, 55404-4597
University of Minnesota Children's Hospital
Minneapolis, Minnesota, United States
United States, Missouri
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, United States, 64108
United States, New York
Children's Hospital New York-Presbyterian
New York, New York, United States, 10032
New York University Medical Center
New York, New York, United States, 10016
Memorial Sloan Kettering
New York, New York, United States
United States, North Carolina
Levine Children's Hospital at Carolinas Medical Center
Charlotte, North Carolina, United States, 28203
United States, Ohio
Nationwide Childrens Hospital
Columbus, Ohio, United States
United States, Oregon
Oregon Health and Science University
Portland, Oregon, United States
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
United States, Tennessee
St. Jude
Memphis, Tennessee, United States, 38105-3678
Vanderbilt Children's Hospital
Nashville, Tennessee, United States
United States, Texas
University of Texas at Southwestern
Dallas, Texas, United States
Cook Children's Medical Center
Forth Worth, Texas, United States, 76104
United States, Washington
Seattle Children's Hospital
Seattle, Washington, United States, 98105
Sponsors and Collaborators
Therapeutic Advances in Childhood Leukemia Consortium
Investigators
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
  More Information

No publications provided

Responsible Party: Nobuko Hijiya, MD, Associate Professor of Pediatrics, Therapeutic Advances in Childhood Leukemia Consortium
ClinicalTrials.gov Identifier: NCT01743807     History of Changes
Other Study ID Numbers: T2009-008
Study First Received: November 28, 2012
Last Updated: August 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Therapeutic Advances in Childhood Leukemia Consortium:
Relapsed
Minimal Residual Disease
MRD
Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
ALL
AML
GNKG168
Pediatric
Childhood

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on October 23, 2014