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

NCT03505554

Last updated date
Study Location
Asst-Monza
Monza, Italy/MB, 20900, Italy
Contact
+390392339277

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
ALK-Positive Anaplastic Large Cell Lymphoma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


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.

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ALK-Positive Anaplastic Large Cell LymphomaA Study of Oral Lorlatinib in Patients With Relapsed ALK Positive Lymphoma
NCT03505554
  1. Monza, Italy/MB
ALL GENDERS
18 Years+
years
MULTIPLE SITES
ALK-Positive Anaplastic Large Cell LymphomaProspective Study of the Prognostic Value of New Markers in Adults With ALK-positive Large Anaplastic Lymphoma
NCT03603847
  1. Amiens,
  2. Clermont-Ferrand,
  3. Grenoble,
  4. Lille,
  5. Marseille,
  6. Paris Cedex 10,
  7. Paris,
  8. Pessac,
  9. Pierre Bénite,
  10. Rennes,
  11. Rouen,
  12. Strasbourg,
  13. Toulouse,
  14. Vandoeuvre les Nancy,
  15. Creteil,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE A Study of Oral Lorlatinib in Patients With Relapsed ALK Positive Lymphoma
Official Title  ICMJE A Phase 2 Open Label Study of Oral Lorlatinib in Patients With Relapsed ALK Positive Lymphoma Previously Treated With ALK Inhibitors (CRU3)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Anaplastic Large Cell Lymphoma, ALK-Positive
Intervention  ICMJE Drug: Lorlatinib
100 mg QD
Other Name: PF-06463922
Study Arms  ICMJE Experimental: Lorlatinib
100 mg QD
Intervention: Drug: Lorlatinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 20, 2018)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Silvia Mori, PhD+390392339277[email protected]
Contact: Silvia Baretta, SC+390392339743[email protected]
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03505554
Other Study ID Numbers  ICMJE CRU3
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Milano Bicocca
Study Sponsor  ICMJE University of Milano Bicocca
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:CARLO GAMBACORTI-PASSERINI, MDUniversity of Milano Bicocca
PRS Account University of Milano Bicocca
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP