Relapsed or Refractory Acute Lymphoblastic Leukemia MedDRA version: 21.0 Level: LLT Classification code 10025230 Term: Lymphatic leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Kyprolis
Product Name: Carfilzomib Lyophilisate for Solution for Injection
Product Code: PR-171
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: carfilzomib
CAS
Sponsors
Onyx Therapeutics, Inc., an Amgen Inc. subsidiary
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 110 Subject's legally acceptable representative has provided informed consent when the subject is legally too young to provide informed consent and the subject has provided written assent based on local regulations and/or guidelines prior to any study-specific activities/procedures being initiated, except for standard of care local testing as permitted per Section 21.3. 111 Age greater than or equal to 1 month to less than 21 years. Subjects greater than or equal to 18 years must have had their original diagnosis at less than 18 years of age. 112 Subjects must be diagnosed with relapsed or refractory relapsed ALL. 113 Subjects must have a documented first remission, less than 5% blasts in the bone marrow (M1 bone marrow) and no evidence of extramedullary disease. 114 T-cell ALL with bone marrow relapse (defined as greater than or equal to 5% leukemia blasts in bone marrow) or refractory relapse with or without extramedullary disease. OR B-cell ALL with bone marrow relapse or refractory relapse (defined as greater than or equal to 5% leukemia blasts in bone marrow) after having received a targeted B-cell immune therapy (eg, blinatumomab, inotuzumab, or a CAR-T therapy) with or without extramedullary disease. 115 Adequate liver function: bilirubin less than or equal to 1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) less than or equal to 5 x ULN. 116 Adequate renal function: serum creatinine less than or equal to 1.5 x ULN or glomerular filtration rate (GFR) greater than or equal to 70 mL/min/1.73 m2; or for children less than 2 years of age, greater than or equal to 50 mL/min/1.73 m2. 117 Adequate cardiac function: shortening fraction greater than or equal to 30% or ejection fraction greater than or equal to 50%. 118 Karnofsky (subjects greater than or equal to 16 years of age) or Lansky (subjects 12 months to less than 16 years of age) performance status greater than or equal to 50%. 119 Subjects must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy treatment before enrolment (for example: recovery from gastrointestinal toxicity may occur more rapidly than less reversible organ toxicities such as sinusoidal obstruction syndrome or non-infectious pneumonitis, for serious prior toxicities recommend discussion with Amgen medical monitor). 120 Life expectancy of greater than 6 weeks per investigator`s judgment at time of screening Are the trial subjects under 18? yes Number of subjects for this age range: 144 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 211 Prior treatment with carfilzomib. 214 Intolerance, hypersensitivity, or inability to receive any of the chemotherapy components of the VXLD regimen. An exception is allowed for allergy to asparaginase products if Erwinia asparaginase is unable to be administered. 215 Autologous HSCT within 6 weeks prior to start of study treatment. 216 Allogeneic HSCT within 3 months prior to start of study treatment. 217 Active GVHD requiring systemic immune suppression. 218 470 msec. 231 History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion. 232 Female subject is pregnant/breastfeeding or planning to become pregnant/breastfeed during treatment and for an additional 6 months after the last dose of any study treatment or for 12 months after last dose of cyclophosphamide if administered during optional consolidation cycle. 233 Female subjects of childbearing potential unwilling to use 1 highly effective method of contra
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 and to recommend a phase 2 dose of carfilzomib in combination with induction chemotherapy Phase 2: - Compare the rate of CR of CFZ-VXLD at the end of induction therapy to an appropriate external control. ;Secondary Objective: Phase 2: -Evaluate the safety and tolerability of CFZ-VXLD -Compare the rate of CR, CRp, CRh, and CRi of CFZ-VXLD at the end of induction therapy relative to an appropriate external control -Compare EFS for CFZ VXLD to an appropriate external control -Compare OS for CFZ-VXLD relative to an appropriate external control -Estimate the DOR for CFZ-VXLD relative to an appropriate external control -Estimate the rate of MRD[-] at the end of induction in subjects receiving CFZ-VXLD •Estimate the proportion of subjects that bridge to stem cell transplant or CAR-T cell therapy in subjects receiving CFZ-VXLD •Estimate the rate of CR, CRp, CRh, and CRi of CFZ-VXLD at the end of consolidation therapy in subjects receiving CFZ-VXLD. •Estimate the pharmacokinetics of carfilzomib when administered as part of VXLD regimen ;Primary end point(s): • CR after induction therapy;Timepoint(s) of evaluation of this end point: Phase 2: The OR for the PoCR for CFZ-VXLD versus external control. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Treatment-emergent and treatment-related adverse events and severe adverse events and laboratory abnormalities during the induction therapy and consolidation therapy •CR, CRp, CRh, and CRi at the end of induction therapy •EFS, defined as time from initiation of therapy until treatment failure (defined as failure to reach at least a CRi after consolidation or after induction in subjects that do not receive consolidation), relapse, or death from any cause •OS defined as time from initiation of therapy until death from any cause •DOR, defined as time from earliest of CR, CRp, CRh, or CRi to relapse or death from any cause •MRD status using NGS less than 10-3 and less than 10-4 by NGS in subjects achieving CR, CRp, CRh, or CRi after induction and consolidation therapy •MRD status using NGS >10^-4 after induction therapy in subjects achieving CR •Occurrence of a stem cell transplant or CAR-T, without an intervening relapse after the end of protocol specified therapy •CR, CRp, CRh, and CRi after consolidation therapy •Carfilzomib pharmacokinetic parameters, including AUC, Cmax and if feasible t1/2;Timepoint(s) of evaluation of this end point: End of the Induction Cycle | — |
Countries
Australia, Austria, Bulgaria, Canada, Czechia, Czech Republic, Denmark, France, Greece, Israel, Italy, Netherlands, Norway, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, Turkey, United Kingdom, United States
Contacts
Public ContactMedical Information
Amgen AB
Outcome results
None listed