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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Therapeutic Advances in Childhood Leukemia Consortium
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: May 28, 2013
Last verified: May 2013
  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 ]

Estimated Enrollment: 36
Study Start Date: November 2012
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: December 2015 (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

Contacts
Contact: Jeannette van der Giessen, BA 323-361-8725 jvandergiessen@chla.usc.edu
Contact: Elena Eckroth 323-361-5429 eeckroth@chla.usc.edu

  Hide Study Locations
Locations
United States, Arizona
Phoenix Children's Hospital Not yet recruiting
Phoenix, Arizona, United States
Principal Investigator: Jessica Boklan, MD         
United States, California
Miller Children's Hospital Not yet recruiting
Long Beach, California, United States
Principal Investigator: Amanda Termuhlen, MD         
Childrens Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Principal Investigator: Paul S. Gaynon, MD         
Sub-Investigator: Theresa Harned, MD         
Oakland Children's Hospital Not yet recruiting
Oakland, California, United States
Principal Investigator: Jacob Garcia, MD         
Stanford University Medical Center Not yet recruiting
Palo Alto, California, United States, 94304-1812
Principal Investigator: Clare Twist, MD         
UCSF School of Medicine Not yet recruiting
San Francisco, California, United States, 94143-0106
Principal Investigator: Steven DuBois, MD         
United States, Colorado
The Children's Hospital, University of Colorado Not yet recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Lia Gore, MD         
United States, District of Columbia
Children's National Medical Center Not yet recruiting
Washington, District of Columbia, United States
United States, Florida
University of Miami Cancer Center Not yet recruiting
Miami, Florida, United States, 33136
Principal Investigator: John Goldberg, MD         
United States, Georgia
Children's Healthcare of Atlanta, Emory University Not yet recruiting
Atlanta, Georgia, United States
Principal Investigator: Todd Cooper, MD         
United States, Illinois
Children's Memorial Not yet recruiting
Chicago, Illinois, United States
Principal Investigator: Nobuko Hijiya, MD         
United States, Maryland
Johns Hopkins University Not yet recruiting
Baltimore, Maryland, United States
Principal Investigator: Pat Brown, MD         
United States, Massachusetts
Dana Farber Not yet recruiting
Boston, Massachusetts, United States
Principal Investigator: Lewis Silverman, MD         
United States, Michigan
C.S. Mott Children's Hospital Recruiting
Ann Arbor, Michigan, United States, 48109-0914
Principal Investigator: Raymond Hutchinson, MD         
United States, Minnesota
Childrens Hospital & Clinics of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55404-4597
Principal Investigator: Bruce Bostrom, MD         
Principal Investigator: Yoav Messinger, MD         
University of Minnesota Children's Hospital Not yet recruiting
Minneapolis, Minnesota, United States
Principal Investigator: Mike Burke, MD         
United States, Missouri
Children's Mercy Hospitals and Clinics Not yet recruiting
Kansas City, Missouri, United States, 64108
Principal Investigator: Kathleen Neville, MD         
United States, New York
Children's Hospital New York-Presbyterian Recruiting
New York, New York, United States, 10032
Principal Investigator: Julia Glade-Bender, MD         
Children's Hospital New York-Presbyterian Not yet recruiting
New York, New York, United States, 10032
Principal Investigator: Julia Glade-Bender, MD         
Memorial Sloan Kettering Not yet recruiting
New York, New York, United States
New York University Medical Center Not yet recruiting
New York, New York, United States, 10016
Principal Investigator: Elizabeth Raetz, MD         
United States, North Carolina
Levine Children's Hospital at Carolinas Medical Center Not yet recruiting
Charlotte, North Carolina, United States, 28203
Contact: Javier Oesterheld, MD         
Principal Investigator: Javier Oesterheld, MD         
United States, Ohio
Nationwide Childrens Hospital Not yet recruiting
Columbus, Ohio, United States
Principal Investigator: Sandeep Soni, MD         
United States, Oregon
Oregon Health and Science University Not yet recruiting
Portland, Oregon, United States
Principal Investigator: Eneida Nemecek, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Principal Investigator: Richard Aplenc, MD         
United States, Tennessee
St. Jude Not yet recruiting
Memphis, Tennessee, United States, 38105-3678
Contact: Deepa Bhojwani, MD         
Principal Investigator: Deepa Bhojwani, MD         
Vanderbilt Children's Hospital Not yet recruiting
Nashville, Tennessee, United States
Principal Investigator: Haydar Frangoul, MD         
United States, Texas
University of Texas at Southwestern Not yet recruiting
Dallas, Texas, United States
Cook Children's Medical Center Not yet recruiting
Forth Worth, Texas, United States, 76104
Principal Investigator: Kenneth Heym, MD         
United States, Washington
Seattle Children's Hospital Not yet recruiting
Seattle, Washington, United States, 98105
Principal Investigator: Blythe Thompson, MD         
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: May 28, 2013
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
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 22, 2014