T2012-002, A Pilot Study of Vincristine Sulfate Liposome Injection (Marqibo®) in Combination with UK ALL R3 Induction Chemotherapy for Children, Adolescents, and Young Adults with Relapse of Acute Lymphoblastic Leukemia
Study ID: STU 082016-009
This is a phase i multistage open label design over two Marqibo dose levels. Prior data on relapse acute lymphoblastic leukemia (aLL) patients treated with standard uK aLL R3 and with Childrens' oncology Group (CoG) protocol therapies suggest that approximately 10% of patients treated in first relapse will experience grade 3 or higher toxicity sufficient to prevent the start of subsequent therapy by day 49. Data from patients treated in second or greater relapse, which will represent the majority of patients on this study, suggest higher delay rates, but are imprecise due to the small number of patients. For the purpose of this study, the current design is calibrated to reject uK aLL R3/Marqibo as a feasible regimen with high probability (greater than or equal to 0.90) if 55% or fewer patients in the target population can be treated successfully, and to accept uK aLL R3/Marqibo as a feasible regimen with high probability (greater than or equal to 0.90) if 80% or more of patients can be treated successfully.
- Patients must be greater than or equal to 1 and younger than or equal to 21 years of age at the time of enrollment. - Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) with greater than or equal to 5% blasts in the bone marrow (M2 or M3), with or without extramedullary disease (excluding active Central Nervous System (CNS) 3 involvement). Subjects with first relapse must have an M3 marrow to be eligible. - Karnofsky greater than 50% for patients greater than 16 years of age and Lansky greater than 50% for patients less than or equal to 16 years of age. - Patients must have recovered from the acute toxic effects (less than Grade 2 or baseline) of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, unless otherwise specified. Subjects with disease related cytopenias will be eligible. - Patients must have relapsed disease after attaining at least a first remission. They may be in first to third relapse. - Patients with Philadelphia chromosome t(9;22) positive disease must have received at least two prior tyrosine kinase inhibitors. - Patients who have experienced their relapse after a Hematopoietic stem cell transplant (HSCT) are eligible, provided they have no evidence of graft-versus-host disease (GVHD) and are at least 100 days post-transplant at the time of enrollment. - Prior anthracycline lifetime cumulative exposure: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy (See Appendix 2 for anthracycline calculation worksheet). - Hematopoietic growth factors: It must have been at least seven days since the completion of therapy with Granulocyte-colony stimulating factor (GCSF) or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta). - Biologic anti-neoplastic agents: At least seven days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond seven days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair or vice chair. - Monoclonal antibodies: At least three half-lives (or 30 days-whichever is longer) of the antibody must have elapsed after the last dose of monoclonal antibody. (e.g., Rituximab = 66 days, Epratuzumab = 69 days) - Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines, chimeric antigen receptor T-cells. - Recent prior chemotherapy: At least 14 days after standard vincristine and the completion of any type of chemotherapy induction regimen. At least 3 weeks after radiation therapy. At least 30 days after the completion of any investigational neoplastic agent is also required. An investigational agent is defined as any drug that is not approved and licensed for sale by the FDA for institutions in the United States, by Health Canada for institutions in Canada and by The Therapeutic Goods Administration for institutions in Australia. - Exceptions: 1. There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such; it is allowable to enroll a patient that has received intrathecal (IT) ARA-C, IT MTX or triple IT therapy within 14 days of enrollment as part of their evaluation to diagnose disease relapse. The IT therapy given within 14 days of initiation of protocol specified chemotherapy, will substitute for the day 1 IT. 2. Subjects with rapidly progressive disease may receive hydroxyurea until they begin study therapy; 3. Patients who relapse while on maintenance-type ALL therapy or are receiving maintenance therapy for disease stabilization will not require a wash-out period before entry into this study. However, there must be at least 14 days after any dose of standard vincristine. - Renal function: Patient[Single Quote]s serum creatinine must be less than or equal to 1.5 x institutional upper limit of normal (ULN) according to age. If the serum creatinine is greater than 1.5 times normal, the patient must have a calculated creatinine clearance or radioisotope GFR greater than or equal to 70mL/min/1.73m2. Alternatively, a 24-hour creatinine clearance may also be used. 1. Pediatric Population (age less than 18): Calculated creatinine clearance greater than or equal to 70 ml/min/1.73m2 as calculated by the Schwartz formula for estimated glomerular filtration rate (GFR) where GFR (ml/min/1.73 m2) = k*Height (cm)/serum creatinine (mg/dl). k is a proportionality constant which varies with age and is a function of urinary creatinine excretion per unit of body size; 0.45 up to 12 months of age; 0.55 children and adolescent girls 0.70 adolescent boys. 2. Adult Population (age greater than or equal to 18): If serum creatinine greater than 1.5 X ULN, then the estimated glomerular filtration rate (GFR) must be greater than 70 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black). - Hepatic function: ALT and AST must be less than 3 x institutional upper limit of norm ULN. Total bilirubin must be less than or equal to 1.5 x ULN (except in the case of subjects with documented Gilbert[Single Quote]s disease less than or equal to 5 x ULN). - Cardiac function - Patients must have a shortening fraction greater than or equal to 27% or an ejection fraction greater than or equal to 55% by echocardiogram, cardiac MRI or MUGA. - Reproductive function: a. Female patients must not be pregnant and those of childbearing potential must have a negative urine or serum pregnancy test confirmed within one week 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 childbearing potential must agree to use an effective method of contraception during the study.
- Cancer Related
- Healthy Volunteers
- UT Southwestern Principal Investigator
- Theodore W Laetsch
CHILDRENS HOSPITAL LOS ANGELES