Clinical trial with the drug lorlatinib in patients affected by a lymphoma that expresses the protein ALK, previously treated with ALK inhibitors but for whom the therapy is not anymore effective

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universita Degli Studi Di Milano Bicocca

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 Sep 2019 → 31 Dec 2025

Decision date (initial)

2025-01-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2025-520788-42-00

EudraCT number

2016-003970-41

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

Define the objective response rates (ORR) of PF-06463922 in subjects with ALK+ lymphomas resistant or refractory to ALK inhibitors

Secondary objectives 5

1. Define the Progression Free Survival (PFS) in subjects with ALK+ lymphomas resistant or refractory to ALK inhibitors
2. Define the overall survival (OS) in ALK+ lymphoma patients treated with PF-06463922, that are resistant or refractory to ALK inhibitors
3. Determine the toxicity profile of PF-06463922 in ALK+ lymphoma patients resistant or refractory to ALK inhibitors
4. Determine the Quality of Life (QoL) in this population of patients using the EORTC–C30 Quality of Life questionnaire
5. Study the mutational status of ALK pre/post PF-06463922 treatment through nextgeneration sequencing (NGS)

Conditions and MedDRA coding

Anaplastic Large Cells Lymphoma (ALCL) ALK+

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

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. Patiets with prior exposure to Brentuximab are eligible for inclusion. The use of Brentuximab is permitted either as first-line or as a subsequent therapy. Refractory/resistant disease is defined as either (i) no achievement of CR or PR during or at the end of at least one prior line of cytotoxic chemotherapy and one prior ALK inhibitor, or (ii) documented progression occurring within 6 months from completion of such treatments
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 anticancer 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

Exclusion criteria 10

1. Current treatment on another therapeutic clinical trial
2. Clinically significant cardiovascular disease (that is, active or <3 months prior to enrollment): cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure (New York Heart Association Classification Class = II)
3. Ongoing cardiac dysrhythmias of NCI CTCAE Grade =2: second-degree or third-degree AV block (unless paced) or any AV block with PR >220 msec, uncontrolled atrial fibrillation of any grade, bradycardia defined as <50 bpm (unless patient is otherwise healthy such as long-distance runners, etc.), machine-read ECG with QTc >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 2, in order to avoid excluding patients with only mild metabolic alterations
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR

Secondary endpoints 5

1. PFS
2. OS
3. Toxicity
4. QoL
5. Mutational analysis

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universita Degli Studi Di Milano Bicocca

Sponsor organisation

Universita Degli Studi Di Milano Bicocca

Address

Piazza Dell'ateneo Nuovo 1

City

Milan

Postcode

20126

Country

Italy

Scientific contact point

Organisation

Universita Degli Studi Di Milano Bicocca

Contact name

Carlo Gambacorti Passerini

Public contact point

Organisation

Universita Degli Studi Di Milano Bicocca

Contact name

Carlo Gambacorti Passerini

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications