Anaplastic Large Cell Lymphoma, ALK-PositivePhase 2CRU3NCT03505554
A Study of Oral Lorlatinib in Patients With Relapsed ALK Positive Lymphoma
A Phase 2 study testing Lorlatinib in people with Anaplastic Large Cell Lymphoma, ALK-Positive, run by University of Milano Bicocca at 2 sites in Italy.
Trial summary
The purpose of this study is to define the objective response rates (ORR) of Lorlatinib in subjects with ALK+ lymphomas resistant or refractory to ALK inhibitors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anaplastic Large Cell Lymphoma, ALK-Positive
- What is being tested?
- Lorlatinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 2 sitesItaly
- Study dates
- 28 Sep 2019to 31 Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed and dated Informed Consent approved by Local Ethical Committee before any protocol-specific screening procedures.
- ALK+ Lymphoma diagnosed by IHC or FISH.
- 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.
- 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.
- Able to take oral therapy.
- Female or male, 18 years of age or older.
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- ECOG performance status 0-3.
- 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.
- 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.
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
- 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.
Who cannot join
- Current treatment on another therapeutic clinical trial.
- 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)
- 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.
- Pregnancy or breastfeeding.
- 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.
- Prior malignancy other than basal cell carcinoma , if original diagnosis happened in the last 5 years.
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- Patients with predisposing characteristics for acute pancreatitis according to investigator judgment (e.g. uncontrolled hyperglycemia, current gallstone disease, alcoholism).
- Hypertriglyceridemia ≥ grade 1.
- 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.
- 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.
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Irccs San Gerardo Dei Tintori
Monza, Italy/MB, 20900
UOC Ematologia, Ospedale S. Eugenio
Roma
About this study
Official title: A Phase 2 Open Label Study of Oral Lorlatinib in Patients With Relapsed ALK Positive Lymphoma Previously Treated With ALK Inhibitors (CRU3)
The purpose of this study is to define the objective response rates (ORR) of Lorlatinib in subjects with ALK+ lymphomas resistant or refractory to ALK inhibitors.
Read the detailed description
Lorlatinib is a selective and potent tyrosine kinase inhibitor of ALK and ROS1 that pre-clinically demonstrated dose-dependent inhibition of mutations that confer resistance to other ALK inhibitors; it is also a brain-penetrant thus it might be active in patients with CNS metastases.
Study Objectives Primary Define the objective response rates (ORR) of PF-06463922 in subjects with ALK+ lymphomas resistant or refractory to ALK inhibitors.
Secondary
- 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 Lorlatinib, that are resistant or refractory to ALK inhibitors.
- Determine the toxicity profile of Lorlatinib 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 Lorlatinib treatment through next-generation sequencing (NGS).
Study design This is a phase 2 study open to 12 eligible patients with lymphoma with a confirmed ALK rearrangement. All patients must have been pretreated with at least one line of standard cytotoxic chemotherapy and at least one ALK inhibitor and they must have demonstrated progression (regardless of initial response) or resistance on the last treatment.
The study begins with a screening period to assess eligibility, up to and including 28 days prior to the first dose of Lorlatinib. Treatment will continue until patient experiences unacceptable toxicity or progressive disease (PD), starts a new anti-cancer therapy or dies.
The study will remain open until all patients have completed 3 years from the enrollment.
Study treatment Patients will receive an oral administration of Lorlatinib at a dose of 100mg QD. In case of toxicity, it is possible to proceed to a dose reduction (75mg or 50mg QD) or a temporary interruption of Lorlatinib.
- Being tested
- Lorlatinib
- Keywords
- ALK, relapsed, lorlatinib
- Medical subject headings
- Lymphoma, Large-Cell, Anaplastic, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LorlatinibDrug
Also called PF-06463922
100 mg QD
| Study group | Role | What they receive |
|---|---|---|
| Lorlatinib | Experimental | 100 mg QD Receives: Drug: Lorlatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
ORR
Measured: 1 year
Secondary outcomes (5)
Progression Free Survival
PFS
Measured: 1 year
Overall Survival
OS
Measured: 1 year
Toxicity, Side Effects and Adverse Events
number, type and grade of adverse events
Measured: up to 24 months
Patients' Reported Outcome in terms of Quality of life
Use of EORTC-QLQ-C30 questionnaire
Measured: up to 24 months
Study the mutational status of ALK pre/post Lorlatinib
Mutational Analysis
Measured: up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2018
- Study start28 Sep 2019
- Primary completion31 Dec 2025
- Study completion31 Dec 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anaplastic Large Cell Lymphoma, ALK-PositiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Milano Bicocca
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- CARLO GAMBACORTI-PASSERINI, MD, Principal investigator, University of Milano Bicocca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03505554
- Sponsor's protocol ID
- CRU3
- Acronym
- CRU3
- Status last verified
- May 2026
- First submitted
- 6 Apr 2018
- Last updated
- 10 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (including data dictionaries) that underlie the results reported in this trial will be made available upon request provided by qualified researchers. The study protocol, statistical analysis plan and informed consent form will be also available. Data will be shared with researchers who provide methodologically sound proposal for achieving the aims of an approved proposal. Proposals should be directed to carlo.gambacorti@unimib.it. Access will be granted following review and approval by the study sponsor and execution of a data access agreement.
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Open Label Study of Oral Lorlatinib in Patients With Relapsed ALK Positive Lymphoma Previously Treated With ALK Inhibitors (CRU3)
- ClinicalTrials.gov ID
- NCT03505554
- Acronym / sponsor ID
- CRU3 / CRU3
- Keywords
- ALK, relapsed, lorlatinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- University of Milano BicoccaUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 28 Sep 2019 (actual)
- Primary completion
- 31 Dec 2025 (actual)
- Study completion
- 31 Dec 2025 (actual)
- First posted
- 23 Apr 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to define the objective response rates (ORR) of Lorlatinib in subjects with ALK+ lymphomas resistant or refractory to ALK inhibitors.
Detailed description
Lorlatinib is a selective and potent tyrosine kinase inhibitor of ALK and ROS1 that pre-clinically demonstrated dose-dependent inhibition of mutations that confer resistance to other ALK inhibitors; it is also a brain-penetrant thus it might be active in patients with CNS metastases.
Study Objectives Primary Define the objective response rates (ORR) of PF-06463922 in subjects with ALK+ lymphomas resistant or refractory to ALK inhibitors.
Secondary
- 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 Lorlatinib, that are resistant or refractory to ALK inhibitors.
- Determine the toxicity profile of Lorlatinib 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 Lorlatinib treatment through next-generation sequencing (NGS).
Study design This is a phase 2 study open to 12 eligible patients with lymphoma with a confirmed ALK rearrangement. All patients must have been pretreated with at least one line of standard cytotoxic chemotherapy and at least one ALK inhibitor and they must have demonstrated progression (regardless of initial response) or resistance on the last treatment.
The study begins with a screening period to assess eligibility, up to and including 28 days prior to the first dose of Lorlatinib. Treatment will continue until patient experiences unacceptable toxicity or progressive disease (PD), starts a new anti-cancer therapy or dies.
The study will remain open until all patients have completed 3 years from the enrollment.
Study treatment Patients will receive an oral administration of Lorlatinib at a dose of 100mg QD. In case of toxicity, it is possible to proceed to a dose reduction (75mg or 50mg QD) or a temporary interruption of Lorlatinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lorlatinib | Experimental | Drug: Lorlatinib100 mg QD |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Signed and dated Informed Consent approved by Local Ethical Committee before any protocol-specific screening procedures.
- ALK+ Lymphoma diagnosed by IHC or FISH.
- 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.
- 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.
- Able to take oral therapy.
Key exclusion criteria (10 listed)
- Current treatment on another therapeutic clinical trial.
- 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)
- 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.
- Pregnancy or breastfeeding.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LorlatinibAlso: PF-06463922100 mg QD | Drug | Lorlatinib |
Primary outcome
Objective Response Rate
Time frame: 1 year
ORR
5 secondary outcomes
Progression Free Survival
Time frame: 1 year
Overall Survival
Time frame: 1 year
Toxicity, Side Effects and Adverse Events
Time frame: up to 24 months
Patients' Reported Outcome in terms of Quality of life
Time frame: up to 24 months
Study the mutational status of ALK pre/post Lorlatinib
Time frame: up to 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2026.
- Individual participant dataSharing planned: Yes. De-identified individual participant data (including data dictionaries) that underlie the results reported in this trial will be made available upon request provided by qualified researchers. The study protocol, statistical analysis plan and informed consent form will be also available. Data will be shared with researchers who provide methodologically sound proposal for achieving the aims of an approved proposal. Proposals should be directed to carlo.gambacorti@unimib.it. Access will be granted following review and approval by the study sponsor and execution of a data access agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
CARLO GAMBACORTI-PASSERINI, MD principal investigator
University of Milano Bicocca
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lorlatinib in people with Anaplastic Large Cell Lymphoma, ALK-Positive, run by University of Milano Bicocca at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2026.