Relapsed or Refractory Acute Lymphoblastic Leukemia MedDRA version: 17.1 Level: LLT Classification code 10025230 Term: Lymphatic leukemia System Organ Class: 100000004864
Conditions
Sponsors
Onyx Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18 years or younger at the time of study treatment initiation. 2. Subjects must have a diagnosis of relapsed (Phase 1b and 2) or refractory (Phase 1b only) ALL with = 5% blasts in the bone marrow (M2 or M3 disease), with or without extramedullary disease. ?- To be eligible for Phase 1b, subjects must have had 1 or more prior therapeutic attempts, defined as: o Early first relapse ( 1.5 × ULN, the subject must have a calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) = 70 mL/min/1.73 m2. 5. Adequate liver function, defined as both of the following: ? Total bilirubin = 1.5 × institutional ULN ? AST and ALT = 5 × institutional ULN 6. Performance status: Karnofsky or Lansky scores = 50 for subjects > 16 years old or = 16 years old, respectively. Are the trial subjects under 18? yes Number of subjects for this age range: 39 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Known allergy to any of the drugs used in the study. (Subjects who have had a previous allergy to PEG-asparaginase but can receive Erwinia are eligible.) 2. Known allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib; for a complete listing of Captisol-enabled drugs, see the Ligand Pharmaceuticals, Inc. website) 3. Left ventricular fractional shortening 2 × the institutional ULN 5. Active treatment for graft-versus-host disease 6. Positive culture for bacteria or fungus within 14 days of the initiation of therapy 7. Down Syndrome 8. Prior therapy restrictions: ? -Subjects must have completed therapy with granulocyte-colony stimulating factor (G-CSF) or other myeloid growth factors at least 7 days before enrollment, or at least 14 days before enrollment, if pegylated myeloid growth factors were administered. ? -Subjects must have received the last dose of a non-monoclonal antibody biologic agent at least 7 days before enrollment. For agents that have known adverse events occurring beyond 7 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 approved by the Onyx study medical monitor. ? -At least 3 antibody half-lives must have elapsed since the last dose of monoclonal antibody (i.e., 66 days for rituximab and 69 days for epratuzumab) before subjects may enroll in the study. ? -Subjects must have completed any type of active immunotherapy (e.g., tumor vaccines) at least 42 days before enrollment. ? -Subjects must not have received any other antineoplastic agents within 7 days prior to enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1b - To assess the safety and tolerability of carfilzomib, alone and in combination with induction chemotherapy, for the treatment of children with relapsed or refractory acute lymphoblastic leukemia (ALL) -To determine the maximum tolerated dose (MTD) of carfilzomib in combination with induction chemotherapy. Phase 2 -To estimate the combined rate of bone marrow CR and bone marrow CRp at the end of the Induction Cycle;Secondary Objective: Phase 1b -To characterize the pharmacokinetics (PK) of carfilzomib alone and in combination with induction chemotherapy -To evaluate the combined rate of bone marrow complete response (CR) and bone marrow CR without platelet recovery (CRp) at the end of the Induction Cycle -To estimate the proportion of subjects who achieve minimal residual disease (MRD) status 33%–100%) is less than 40% Phase 2 ? -Combined proportion of subjects who achieve CR or CRp at the end of the Induction Cycle;Timepoint(s) of evaluation of this end point: End of the Induction Cycle | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1b ? -Pharmacokinetic parameters, principally maximum plasma concentration (Cmax) and area under the curve (AUC), alone and in combination with induction chemotherapy, derived from levels of carfilzomib assayed in PK samples ? -Combined proportion of subjects who achieve CR or CRp at the end of the Induction Cycle ? -Proportion of subjects who achieve MRD status < 10-3 and < 10-4 lymphoblasts at the end of the Induction Cycle as assessed by quantitative immunoglobulin/T-cell receptor (Ig/TcR) polymerase chain reaction (PCR) Phase 2 ? -Proportion of subjects who achieve MRD status < 10-3 and < 10-4 lymphoblasts at the end of the Induction Cycle as assessed by quantitative Ig/TcR PCR ? -Safety and tolerability of carfilzomib in combination with induction chemotherapy as defined by the type, incidence, severity, and outcome of AEs; changes from baseline in key laboratory analytes, vital signs, and physical findings ? -Pharmacokinetic parameters, principally Cmax and AUC, of carfilzomib in combination with induction chemotherapy derived from levels of carfilzomib assayed in PK samples.;Timepoint(s) of evaluation of this end point: End of the Induction Cycle | — |
Countries
Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, Denmark, France, Germany, Greece, Italy, Netherlands, Norway, Poland, Portugal, Romania, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactDawn Pinchasik, MD
Onyx Pharmaceuticals, Inc
Outcome results
None listed