Anaplastic Large Cells Lymphoma (ALCL) ALK+ MedDRA version: 20.0 Level: PT Classification code 10073478 Term: Anaplastic large-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: PF-06463922
Product Code: [lorlatinib]
Pharmaceutical Form: Tablet
INN or Proposed INN: PF-06463922
Current Sponsor code: PF-06463922
Other descriptive name: PF-06463922 form (anhydrous
Sponsors
UNIVERSITÀ DEGLI STUDI MILANO BICOCCA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed and dated Informed Consent approved by Local Ethical Committee before any protocol-specific screening procedures. 2) ALK+ Lymphoma diagnosed by IHC or FISH. 3) Refractory disease or relapse after at least one prior chemotherapy regimen (typically a minimum of 6 cycles of CHOP) and at least one ALK inhibitor; presence of measurable disease by physical examination, CT or CT-PET scan. 4) Any prior antitumor medical treatment or major surgeries must have been completed at least 14 days prior to initiation of study medication. This could not be respected if there is clear evidence of disease progression, manifested as growing pain attributable to the tumour, fever, growing tumour lesions, increasing LDH values. Systemic anti-cancer therapy completed within a minimum of 5 half-lives of study entry. 5) Able to take oral therapy. 6) Female or male, 18 years of age or older. 7) ECOG performance status 0-3. 8) Adequate organ function as defined by the following criteria: - Serum aspartate transaminase (AST) and serum alanine transaminase (ALT) = 2.5 x upper limit of normal (ULN) or AST and ALT = 5 x ULN if liver function abnormalities are due to underlying malignancy - Total serum bilirubin 1.5 x ULN (except patients with documented Gilbert’s syndrome - Creatinine = 1.5 x ULN. 9) Adequate bone marrow function: - Absolute neutrophil count (ANC) = 1000/µL - Platelets = 50.000/µL - Hemoglobin = 9.0 g/dL The hematological values will not be considered in case of bone marrow involvement. 10) Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. 11) Female and male patients who are of childbearing potential must agree to use an effective form of contraception (2 forms of contraception) with their partners throughout participation in this study and for at least 90 days after the last dose of treatment. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 11 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 1) Current treatment on another therapeutic clinical trial. 2) Clinically significant cardiovascular disease (that is, active or 220 msec, uncontrolled atrial fibrillation of any grade, bradycardia defined as 470 msec, or congenital long QT syndrome. 4) Pregnancy or breastfeeding. 5) Use of drugs or foods that are known strong or moderate CYP3A4 inhibitors, inducers and substrates; drugs that are CYP2C9 substrates; drugs that are strong CYP2C19 inhibitors; drugs that are strong CYP2C8 inhibitors; and drugs that are P-gp substrates. 6) Prior malignancy other than basal cell carcinoma , if original diagnosis happened in the last 5 years. 7) Patients with predisposing characteristics for acute pancreatitis according to investigator judgment (e.g. uncontrolled hyperglycemia, current gallstone disease, alcoholism). 8) Hypertriglyceridemia = grade 1. 9) Active and clinically significant bacterial, fungal, or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness. 10) Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration.
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PFS; OS; Toxicity; QoL; Mutational analysis;Timepoint(s) of evaluation of this end point: PFS will be evaluated continuosly for the entire study duration; OS will be evaluated continuosly for the entire study duration; Toxicity will be evaluated continuosly for the entire study duration; QoL will be evaluated at screening, M3, M12, M24, M30, M36 and at the end of the study; The analysis will be performed at screening, M3 and at the end of the study | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Define the objective response rates (ORR) of PF-06463922 in subjects with ALK+ lymphomas resistant or refractory to ALK inhibitors.;Secondary Objective: - Define the Progression Free Survival (PFS) in subjects with ALK+ lymphomas resistant or refractory to ALK inhibitors. - Define the overall survival (OS) in ALK+ lymphoma patients treated with PF-06463922, that are resistant or refractory to ALK inhibitors. - Determine the toxicity profile of PF-06463922 in ALK+ lymphoma patients resistant or refractory to ALK inhibitors. - Determine the Quality of Life (QoL) in this population of patients using the EORTC–C30 Quality of Life questionnaire. - Study the mutational status of ALK pre/post PF-06463922 treatment through next-generation sequencing (NGS).;Primary end point(s): ORR;Timepoint(s) of evaluation of this end point: After 4 weeks from the date of the first dose of PF-06463922, at 12 weeks and then every 12 weeks. After 1 year of treatment every 6 months until M24, then only if clinically indicated and at the end of the study. | — |
Countries
Italy
Contacts
Public ContactProf. Carlo Gambacorti Passerini -
Università degli Studi di Milano-Bicocca
Outcome results
None listed