Phase I Study of GNKG168 in Acute Lymphoblastic Leukemia and Acute Myelogenous Leukemia
- Conditions
- Relapsed Acute Lymphoblastic LeukemiaRelapsed Acute Myelogenous Leukemia
- Interventions
- Registration Number
- NCT01743807
- Lead Sponsor
- Therapeutic Advances in Childhood Leukemia Consortium
- 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).
- Detailed Description
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. The completion of this study and the correlative studies will provide a solid foundation for subsequent phase 2 study and the development of clinical applications of CpG-ODN-based immune therapy as a treatment of childhood leukemia. If safety and efficacy of GNKG168 is proven, it will be intriguing to explore its role to maintain CR in a randomized manner.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 4
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Post-HSCT GNKG168 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. No HSCT GNKG168 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.
- Primary Outcome Measures
Name Time Method Number of Patients With Dose Limiting Toxicity (DLT) in the First Two Courses of Therapy 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 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.
- Secondary Outcome Measures
Name Time Method 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) Doctors have developed a test to detect very small amounts of leukemia that still exist even though it looks like remission under a microscope. This test is called Minimal Residual Disease (MRD). MRD is very specific and can detect 1 cancer cell out of 10,000 regular cells. The results of the MRD test on bone marrow can show when a patient has a very small amount of cancer cells left in the bone marrow. We will use this test to evaluate the effect of GNKG168 in killing the small amount of cells left in your bone marrow.
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. We will evaluate the impact of GNKG168 on induction of clinical GVHD using the consensus scoring system developed by NIH (Filipovich et. al., National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. Diagnosis and Staging Working Group Report, Biology of Blood and Marrow Transplantation, Volume 11, Issue 12, Dec. 2005, pp. 945-956)
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 Change in the percent of ALL or AML blasts exhibiting markers of immunogenicity and apoptosis will be analyzed from bone marrow specimens.
Occurrence of Graft Failure in Patients Who Previously Had a HSCT and Received GNKG168 Day 14 Peripheral blood samples will be evaluated for the presence of cGVHD biomarkers. Change in level of MRD, and MRD response following GNKG168
Duration of of Remission in Patients Who Receive GNKG168 Until patient is no longer being followed (off study) * MRD negative Complete Remission : Negative MRD (\<0.01%), no evidence of circulating leukemic blasts or extramedullary disease, and recovery of peripheral counts (ANC ≥ 500/µL and PLT count ≥ 50,000 µL).
* MRD negative Complete Remission without platelet recovery: Insufficient recovery of platelets (\< 50,000/ µL) but otherwise meets the criteria of MRD-CR.
* Stable Disease: Patient does not satisfy the criterion for PD, or has recovery of ANC ≥ 500/µL and fails to qualify for MRD-CR or MRD-CRp.
* Progressive Disease: At least 5% of circulating leukemic cells or ≥5% in a marrow with count recovery, development of new sites of extramedullary disease, or other laboratory or clinical evidence of PD, with or without recovery of ANC or platelets.
* Not evaluable: Patient does not satisfy the criterion for PD, and did not have a marrow evaluation, had inadequate marrow cell count, or had insufficient recovery of ANC for MRD-CR, MRD-CRp or SD classification.
Trial Locations
- Locations (3)
Childrens Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States