T2009-008: A Phase I Study of GNKG168 in Pediatric Patients with Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia (IND#113600)
This research is being done to learn about safety and efficacy of an investigational drug called GNGK168 in the treatment of children and young adults with acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML).
Inclusion Eligibility Criteria The eligibility criteria listed below are interpreted literally and cannot be waived. All entry/eligibility studies must be performed within one week prior to study enrollment unless otherwise specified. Disease evaluations and confirmation of MRD may be done within 2 weeks prior to study enrollment. 3.3.1 Age Patients must be equal to 1 and equal to 21 years of age when originally diagnosed with ALL or AML. 3.3.2 Diagnosis a. Patients must have previously histologically confirmed ALL or AML at original diagnosis or previous relapse. Patient’s with treatment-related AML are eligible. b. 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 ( equal to 0.01%) by flow cytometry as confirmed by Brent Woods’ lab (section 8.8.1). Results must be available at the time of enrollment. 3.3.3 Performance Level Karnofsky equal to 50% for patients greater than 16 years of age and Lansky equal to 50% for patients equal to 16 years of age. (See Appendix I for Performance Scales) 3.3.4 Prior Therapy a. Patients must have fully recovered from the acute toxic effects of all prior anticancer therapy. b. At least 14 days must have elapsed since any treatment with systemic chemotherapy including high-dose steroid (prednisone greater than 0.5 mg/kg or equivalent), radiotherapy, biological therapy or any other investigational therapy. (Note: lowdose steroid; prednisone equal to 0.5 mg/kg/day or equivalent is allowed.) c. At least 28 days must have elapsed since any cellular therapies such as chimeric antigen receptor-modified T cells. d. Patients who have never had a Hematopoietic Stem Cell Transplant (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. e. Previous Hematopoietic Stem Cell Transplant: 1. Patients having received HSCT are eligible and 60 days must have elapsed since stem cell infusion. 2. Patients having received donor lymphocyte infusions (DLI) are eligible. 3. At least 28 days must have elapsed from the last DLI. 4. Must have equal to 90% donor chimerism. The test for donor chimerism must have been done within the last 60 days. If patient has subsequently relapsed after HSCT but prior to enrollment on this study, the donor chimerism test is not needed. Protocol version 10-21-2013 20 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 greater than 0.5 mg/kg or equivalent; see section 3.3.4 b) (Note; lowdose steroid; prednisone equal to 0.5 mg/kg/day or equivalent is allowed.) 3.3.5 Renal and Hepatic Function a. 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. (Grade 1 per the CTCAE 4.0) b. Patient’s ALT and AST must be less than or equal to 3 x institutional upper limit of normal. (Grade 1 per the CTCAE 4.0) c. Patient’s total bilirubin must be less than or equal to 1.5 x institutional upper limit of normal. (Grade 1 per the CTCAE 4.0) 3.3.6 Cardiac Function Patient must have a shortening fraction greater than 27% by ECHO or an ejection fraction greater than 45% by MUGA. 3.3.7 Reproductive Function a. Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment. b. Female patients with infants must agree not to breastfeed their infants while on this study. c. Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study. 3.3.8 Hematological Function Patients must have an absolute neutrophil count greater than 750/dL, platelets greater than 75,000/dL AND absolute lymphocyte count greater than 200/?l which is not decreasing. Patients with previous HSCT may have a platelet count greater than 50,000/dL. 3.4 Exclusion Eligibility Criteria Patients will be excluded if they meet any of the following criteria. 3.4.1 Graft versus host disease (GVHD) that meets the following criteria a. Active grade 2 or higher acute GVHD at the time of study entry. b. Active chronic GVHD (moderate or severe). See Appendix 2 for Chronic GVHD Grading. 3.4.2 Plan for donor lymphocyte infusions during the study period. 3.4.3 Need for immunosuppressive medications including high-dose corticosteroids (prednisone greater than 0.5 mg/kg or equivalent) (Note: low-dose steroid; prednisone equal to 0.5 mg/kg/day or equivalent is allowed.) 3.4.4 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). 3.4.5 Patient will be excluded if they are currently receiving other investigational drugs. Protocol version 10-21-2013 21 3.4.6 Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period. 3.4.7 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. 3.4.8 Patients with CNS 3 disease are excluded. No CNS therapy will be allowed during the first 2 courses of therapy.
This is a phase I study. In a phase I study, the study drug is given at a specific dose and gradually increased until there are unacceptable side effects. Between 3 and 6 participants will receive the same dose and if the side effects are not too severe the next group of participants will receive a higher dose. Depending on when enrolled in this study participants may receive a lower dose of GNGK168 than those who are enrolled later. If participants receive a high dose level of the study drug, it is possible that you may have serious side effects. Dosing is done this way because we do not yet know the best dose to use in children and young adults with ALL or AML. Before Participants start dosing, you will be assigned a dose of GNGK168. The dose of GNGK168 will not change during the study. GNKG168 will be given through an intravenous infusion (IV) every day for 5 days. The IV will last 60 minutes. Dosing will be repeated every 14 days. Participants will receive a minimum of 2 courses of study drug unless you have serious side effects or your leukemia comes back. Participants receive up to 6 courses of study drug.
09/30/2014 04:03 AM