A Phase I Study of GNKG186 in Patient With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2011 by SBI Biotech Co., Ltd..
Recruitment status was  Recruiting
Sponsor:
Information provided by:
SBI Biotech Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01035216
First received: December 17, 2009
Last updated: September 26, 2011
Last verified: September 2011
  Purpose

This is an open-label, dose escalation study designed to characterize the safety, tolerability, efficacy, and pharmacokinetics of GNKG168 in patients with B-CLL that has relapsed or is refractory to all prior standard therapy, or for which no standard therapy exists.


Condition Intervention Phase
Leukemia
Drug: GNKG168
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of GNKG168 Administered by Intravenous Infusion in Patients With Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL)

Resource links provided by NLM:


Further study details as provided by SBI Biotech Co., Ltd.:

Primary Outcome Measures:
  • To determine the dose limiting toxicity (DLT) and recommended phase 2 dose

Estimated Enrollment: 24
Study Start Date: September 2009
Estimated Study Completion Date: July 2012
Estimated Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GNKG168
The starting dose will be 0.25 mg/kg. If the dose is tolerable, subsequent cohorts will be enrolled and treated with 0.5, 0.75, 1.0 and 1.5 mg/kg. If 0.25 mg/kg proves to be intolerable, the dose will be reduced to 0.15 mg/kg.
Drug: GNKG168
GNKG168 will be administered as a 60 minute IV infusion once daily for 5 days followed by a 9 day rest period.
Other Name: CpG ODN

Detailed Description:

This is an open-label, dose escalation study designed to characterize the safety, tolerability, efficacy, and pharmacokinetics of GNKG168 in patients with B-CLL that has relapsed or is refractory to all prior standard therapy, or for which no standard therapy exists.

As secondary objectives, baseline TLR-9 intracellular staining of B-CLL cells, and in vitro assays to assess the potential of B-CLL cells to undergo apoptosis in conjunction with GNKG168 therapy will be examined. Baseline characteristics of B-CLL will be examined including interphase genetics, FISH CLL, IgVH mutational status, expression of ZAP70, β2-microglobulin and the expression of the prognostic marker CD38 in peripheral blood cells (at baseline and during treatment) and baseline immune SNPs (FcγRIIIa, FcγRIIa, TNF-α, IFN-γ, CD40 and others). As pharmacodynamics parameters, the expression of B-cell and T-cell activation markers (including IL-21 receptor upregulation), NK cell markers, and cytokines will be investigated.

This clinical trial will also assess the ability of B CLL patients treated with GNKG168 to elicit anti pneumococcal antibodies in response to adjuvant vaccination with the Prevnar™ vaccine.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients who have cytologically confirmed B-cell chronic lymphocytic leukemia (B-CLL) that has relapsed or been refractory to all prior standard therapy, or for which no standard therapy exists, or patients who refuse available therapy.
  2. Patients' B-CLL must be staged according to either the Rai or Binet systems23 (see Appendix III) and assessed for chromosomal abnormalities, unmutated IgVH status, and expression of ZAP70, and expression of CD38 (see Section 7.2 Pre-treatment).
  3. Patients must have recovered from all acute adverse effects of prior therapies to grade 1, excluding alopecia.
  4. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
  5. Patients must be ≤ to 18 years of age.
  6. Patients must have normal organ function as defined by:

    total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT)≤ 2.5 x ULN serum creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. The creatinine clearance in male patients may be calculated using the Cockcroft-Gault formula: CrCl (mL/min) = [(140 - age) x weight (kg)]/ 72 x Cr (mg/dL). Note: in female patients, this calculation must be multiplied by a factor of 0.85.

  7. Patients must have serum sodium levels ≥ 135 mmol/L and serum chloride levels ≥ 98 mmol/L.
  8. Male patients must have a QTc interval of < 450 msec and female patients must have a QTc interval of < 470 msec.
  9. Patients must be able to understand and willing to sign a written informed consent document.
  10. Patients must be at least 2 weeks from prior chemotherapy, radiation therapy, major surgery, or other investigational anticancer therapy. Patients may receive steroids to control the secondary effects of CLL such as autoimmune cytopenia or painful lymph nodes if this is considered by the treating physician to be in the best interest of the patient.
  11. Women of childbearing potential must have a negative serum or urine pregnancy test within 2 weeks prior to beginning treatment on this study. Male and female patients must use acceptable contraceptive methods during the entire study period and for 1 month after the end of study or after being discontinued from the study.

Exclusion Criteria:

  1. Patients who are currently receiving chemotherapy, radiotherapy, biological therapy, or any other investigational therapy.
  2. Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse effects due to agents administered more than 4 weeks earlier.
  3. Patients with uncontrolled known leukemic meningitis, because of their poor prognosis and likelihood of developing progressive neurologic dysfunction which would confound evaluation of neurologic and other adverse events.
  4. Patients with a history of sensitivity or allergy attributed to compounds of similar chemical composition to GNKG168 or to the Prevnar™ vaccine.
  5. Patients with concurrent serious infections (i.e., requiring an intravenous antibiotic).
  6. Patients with active malignancy (excepting non-melanomatous skin cancers) which may limit survival to less than 2 years.
  7. Patients with pre-existing autoimmune diseases (i.e. systemic lupus erythematosis, rheumatoid arthritis, Crohn's disease or ulcerative colitis, primary sclerosing cholangitis, thyroiditis, scleroderma, etc.) are not eligible.
  8. Women who are pregnant or are of childbearing potential and not using methods to avoid pregnancy, and women who are breastfeeding.
  9. Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris or psychiatric illness/social situations that would limit compliance with study requirements.
  10. Patients with significant cardiac disease including heart failure that meets New York Heart Association (NYHA) class III and IV definitions, history of myocardial infarction within six months of study entry, uncontrolled dysrhythmias or poorly controlled angina.
  11. Patients with known positive status for HIV or active hepatitis B or hepatitis C.
  12. Patients with any medical condition which in the opinion of the Investigator places them at an unacceptably high risk for toxicities.
  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: NCT01035216

Locations
United States, California
Univ. of San Diego: Moores UCSD Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Dr Thomas Kipps    858-534-5400      
Principal Investigator: Thomas Kipps, MD, PhD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Khara Baumann    612-626-6795    nord0241@umn.edu   
Principal Investigator: Veronika Bachanova, MD, PhD         
United States, New York
North Shore University Hospital Recruiting
New Hyde Park, New York, United States, 11042
Contact: Ireen Khan       IKahn@nshs.edu   
Principal Investigator: Jacqueline Barrientos, MD         
Cornell University Not yet recruiting
New York, New York, United States, 10021
Principal Investigator: Richard Furman, MD         
United States, Oregon
Oregon Health & Sciences University Recruiting
Portland, Oregon, United States, 97239
Contact: Dr Stephen Spurgeon    503-494-6101      
Principal Investigator: Stephen Spurgeon, MD         
Sponsors and Collaborators
SBI Biotech Co., Ltd.
  More Information

No publications provided

Responsible Party: SBI Biotech Co., Ltd, Theradex (US Representative Agent
ClinicalTrials.gov Identifier: NCT01035216     History of Changes
Other Study ID Numbers: G07-10075
Study First Received: December 17, 2009
Last Updated: September 26, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by SBI Biotech Co., Ltd.:
Relapsed or Refractory B-Cell Chronic Lymphocytic Leukemia (B-CLL)

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 26, 2014