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

Relapsed Acute Lymphoblastic Leukemia Clinical Trial

Official title:

A Phase I Study of GNKG168 in Pediatric Patients With Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia (IND#113600)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01743807
• Other study ID #: T2009-008
• Status: Terminated
• Phase: Phase 1
• First received: November 28, 2012
• Last updated: November 22, 2015
• Start date: November 2012
• Est. completion date: July 2014

Study information

• Verified date: November 2015
• Source: Therapeutic Advances in Childhood Leukemia Consortium
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year to 21 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Relapsed Acute Lymphoblastic Leukemia
• Relapsed Acute Myelogenous Leukemia

Intervention

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.

Locations

Country	Name	City	State
United States	C.S. Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta, Emory University	Atlanta	Georgia
United States	The Children's Hospital, University of Colorado	Aurora	Colorado
United States	Johns Hopkins University	Baltimore	Maryland
United States	Dana Farber	Boston	Massachusetts
United States	Levine Children's Hospital at Carolinas Medical Center	Charlotte	North Carolina
United States	Children's Memorial	Chicago	Illinois
United States	Nationwide Childrens Hospital	Columbus	Ohio
United States	University of Texas at Southwestern	Dallas	Texas
United States	Cook Children's Medical Center	Forth Worth	Texas
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	Miller Children's Hospital	Long Beach	California
United States	Childrens Hospital Los Angeles	Los Angeles	California
United States	St. Jude	Memphis	Tennessee
United States	University of Miami Cancer Center	Miami	Florida
United States	Childrens Hospital & Clinics of Minnesota	Minneapolis	Minnesota
United States	University of Minnesota Children's Hospital	Minneapolis	Minnesota
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Children's Hospital New York-Presbyterian	New York	New York
United States	Memorial Sloan Kettering	New York	New York
United States	New York University Medical Center	New York	New York
United States	Oakland Children's Hospital	Oakland	California
United States	Stanford University Medical Center	Palo Alto	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Oregon Health and Science University	Portland	Oregon
United States	UCSF School of Medicine	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Therapeutic Advances in Childhood Leukemia Consortium

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of patients with dose limiting toxicity (DLT).		2 months	Yes
Secondary	To measure the reduction of MRD in patients treated with GNKG168.		30 days	No
Secondary	To measure the length or remission in patients who receive GNKG168.		30 days	No
Secondary	To measure the rate of Graft Versus Host Disease (GVHD) in patient with previous HSCT.		30 days	No
Secondary	To measure the rate graft failure in patients who previously had a HSCT and who received GNKG168.		30 days	No