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

NCT01743807 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: T2009-008
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 3

Brief 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).

Conditions

Relapsed Acute Lymphoblastic Leukemia; Relapsed Acute Myelogenous Leukemia

Keywords

Relapsed; Minimal Residual Disease; MRD; Acute Lymphoblastic Leukemia; Acute Myelogenous Leukemia; ALL; AML; GNKG168; Pediatric; Childhood

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Dose Limiting Toxicity (DLT) in the First Two Courses of Therapy

  DLT is defined as: A) Any non-hematologic toxicity that is ≥ CTCAE grade 3 and at least possibly related to GNKG168 (the relationship to GNKG168 cannot be ruled out), with the EXCEPTION of the following toxicities when observed at Grade 3: * Fatigue * Fever * Anorexia * Rash that turns to grade ≤ 2 within 7 days * Elevation in hepatic transaminases (ALT/SGOT and AST/SGPT), GGT or alkaline phosphatase that returns to ≤ grade 2 within 14 days. It will not be considered a DLT if the patient exits the study and begins alternative therapy before the end of the 14 day evaluation period. B) Grade 3 or 4 hematologic toxicity that is at least possibly related to GNKG168 that does not reverse to baseline within 7 days. C) For patients who have undergone HSCT, DLT will include the onset of Grade 3 or 4 acute GVHD, the onset of moderate to severe chronic GVHD, the onset of bronchiolitis obliterans and graft failure.

  Beginning with the first dose of GNKG168 until the end of course 2; courses are 14 days so there will be approximately 28 days of monitoring for DLT

Secondary Outcomes (5)

• The Number of Participants With a Decrease in Minimal Residual Disease (MRD) Present in Patients Treated With GNKG168

  Pre-study and End of Course 1 (Day 14)

• Occurrence of Graft Versus Host Disease (GVHD) in Patients Who Had Previous HSCT and Received GNKG168

  Weekly during Courses 1 and 2 (i.e, 4 times in 28 days), Day 1 of Courses 3-6 (approximately Days 29, 43 and 57), and when patient is removed from protocol therapy.

• Occurrence of Graft Failure in Patients Who Previously Had a HSCT and Received GNKG168

  Day 14

• Change in the Percent of ALL or AML Blasts Exhibiting Markers of Immunogenicity and Apoptosis

  End of Course 1 (Day 14), end of Course 2 (approx. Day 28), end of courses 4 and 6 (approx. Days 56 and 70), and date removed from therapy if previous marrow sample > 2 weeks ago

• Duration of of Remission in Patients Who Receive GNKG168

  Until patient is no longer being followed (off study)

Study Arms (2)

Post-HSCT

EXPERIMENTAL

Patients who have a history of hematopoetic stem cell transplantation (HSCT). GNKG168 will be administered as a 60 minute intravenous infusion daily for 5 consecutive days. It may be repeated every 14 days. Patients should receive minimum 2 courses and up to 6 courses may be administered. Dose will be assigned at study entry.

Drug: GNKG168

No HSCT

EXPERIMENTAL

Patients who have never undergone HSCT. GNKG168 will be administered as a 60 minute intravenous infusion daily for 5 consecutive days. It may be repeated every 14 days. Patients should receive minimum 2 courses and up to 6 courses may be administered. Dose will be assigned at study entry.

Drug: GNKG168

Interventions

GNKG168 DRUG

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. Dose Level 0: 0.15 mg/kg Dose Level 1: 0.25 mg/kg Dose Level 2: 0.75 mg/kg Dose Level 3: 1.5 mg/kg The starting dose level for the trial will be 0.25 mg/kg. If that dose level proves to be intolerable, the dose will be reduced to 0.15 mg/kg (dose level 0). If the 0.15 mg/kg dose level is intolerable due to DLTs, TACL, the Principal Investigator, and Medical Monitor will then decide the best course of action for subsequent administration of GNKG168.

Also known as: CpG685

No HSCT; Post-HSCT

Eligibility Criteria

• Age: 1 Year - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age Patients must be ≥1 and ≤ 21 years of age when originally diagnosed with ALL or AML.
• Diagnosis
• Patients must have previously histologically confirmed ALL or AML at original diagnosis or previous relapse. Patients with treatment-related AML are eligible.
• 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
• Patient must have detectable MRD (≥0.01%) by flow cytometry.
• Performance Level Karnofsky ≥ 50% for patients \>16 years of age and Lansky ≥ 50% for patients ≤16 years of age.
• Prior Therapy
• 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.)
• At least 28 days must have elapsed since any cellular therapies such as chimeric antigen receptor-modified T cells.
• Patients who have never had HSCT must not be a suitable candidate for HSCT. For this protocol, a suitable candidate is defined as one who has an identified donor with plans to undergo transplant within the next 28 days.
• Previous HSCT:
• Patients having received HSCT are eligible and 60 days must have elapsed since stem cell infusion.

You may not qualify if:

• Patients will be excluded if they meet any of the following criteria.
• Graft versus host disease (GVHD) that meets the following criteria:
• Active grade 2 or higher acute GVHD at the time of study entry.
• Active chronic GVHD (moderate or severe).
• 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 CNS 3 disease are excluded. No CNS therapy will be allowed during the first 2 courses of therapy.

Sponsors & Collaborators

• Therapeutic Advances in Childhood Leukemia Consortium: lead
• SBI Biotech Co., Ltd.: collaborator

Study Sites (3)

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Links

• Therapeutic Advances in Childhood Leukemia \& Lymphoma Consortium web site

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Recurrence; Neoplasm, Residual

Interventions

GNKG168

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Limitations and Caveats

Early termination of study, due to SBI Biotech stopped supporting the study led to the small data set for analysis and technical problems with measurement leading to an uninterpretable data.

Results Point of Contact

• Title: Peggy Romano, BA, CCRP
• Organization: Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) / Children's Hospital Los Angeles

promano@chla.usc.edu

323-361-5505

Study Officials

• Nobuko Hijiya, MD

  Ann and Robert H. Lurie Children's Hospital of Chicago

  STUDY CHAIR

• Kirk Schultz, MD

  British Columbia Children's Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Study Record Dates

• First Submitted: November 28, 2012
• First Posted: December 6, 2012
• Study Start: March 26, 2014
• Primary Completion: July 28, 2014
• Study Completion: July 28, 2014
• Last Updated: January 27, 2025
• Results First Posted: January 27, 2025

Record last verified: 2024-12

Locations

US (3)