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A Study of Oral Lorlatinib in Patients With Relapsed ALK Positive Lymphoma (CRU3)

Primary Purpose

Anaplastic Large Cell Lymphoma, ALK-Positive

Status
Recruiting
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Lorlatinib
Sponsored by
University of Milano Bicocca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anaplastic Large Cell Lymphoma, ALK-Positive focused on measuring ALK, relapsed, lorlatinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Exclusion Criteria:

  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 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.

Sites / Locations

  • Asst-MonzaRecruiting
  • UOC Ematologia, Ospedale S. EugenioRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lorlatinib

Arm Description

100 mg QD

Outcomes

Primary Outcome Measures

Objective Response Rate
ORR

Secondary Outcome Measures

Progression Free Survival
PFS
Overall Survival
OS
toxicity
number, type and grade of adverse events
Quality of life
Use of EORTC-QLQ-C30 questionnaire
Study the mutational status of ALK pre/post Lorlatinib
Mutational Analysis

Full Information

First Posted
April 6, 2018
Last Updated
August 4, 2023
Sponsor
University of Milano Bicocca
Collaborators
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT03505554
Brief Title
A Study of Oral Lorlatinib in Patients With Relapsed ALK Positive Lymphoma
Acronym
CRU3
Official Title
A Phase 2 Open Label Study of Oral Lorlatinib in Patients With Relapsed ALK Positive Lymphoma Previously Treated With ALK Inhibitors (CRU3)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 10, 2017 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Milano Bicocca
Collaborators
Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anaplastic Large Cell Lymphoma, ALK-Positive
Keywords
ALK, relapsed, lorlatinib

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Lorlatinib
Arm Type
Experimental
Arm Description
100 mg QD
Intervention Type
Drug
Intervention Name(s)
Lorlatinib
Other Intervention Name(s)
PF-06463922
Intervention Description
100 mg QD
Primary Outcome Measure Information:
Title
Objective Response Rate
Description
ORR
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Progression Free Survival
Description
PFS
Time Frame
1 year
Title
Overall Survival
Description
OS
Time Frame
1 year
Title
toxicity
Description
number, type and grade of adverse events
Time Frame
up to 24 months
Title
Quality of life
Description
Use of EORTC-QLQ-C30 questionnaire
Time Frame
up to 24 months
Title
Study the mutational status of ALK pre/post Lorlatinib
Description
Mutational Analysis
Time Frame
up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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. Exclusion Criteria: 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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Silvia Mori, PhD
Phone
+390392339277
Email
silvia.mori@unimib.it
First Name & Middle Initial & Last Name or Official Title & Degree
Silvia Baretta, SC
Phone
+390392339743
Email
silvia.baretta1@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
CARLO GAMBACORTI-PASSERINI, MD
Organizational Affiliation
University of Milano Bicocca
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asst-Monza
City
Monza
State/Province
Italy/MB
ZIP/Postal Code
20900
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carlo Gambacorti-Passerini, MD
Phone
+390392339553
Email
carlo.gambacorti@unimib.it
First Name & Middle Initial & Last Name & Degree
Carlo Gambacorti-Passerini, MD
Facility Name
UOC Ematologia, Ospedale S. Eugenio
City
Roma
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elisabetta Abruzzese, MD

12. IPD Sharing Statement

Learn more about this trial

A Study of Oral Lorlatinib in Patients With Relapsed ALK Positive Lymphoma

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